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The study for neurotoxicity of advanced glycation end-products (the structural epitope AGE-2) in neurodegenerative processes

Research Project

Project/Area Number 13470197
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Psychiatric science
Research InstitutionHokuriku University

Principal Investigator

TAKEUCHI Masayoshi  Hokuriku University, Faculty of Pharmaceutical Sciences, Department of Biochemistry, Assistant Professor, 薬学部, 講師 (20154982)

Co-Investigator(Kenkyū-buntansha) SASAKI Nobuyuki  Sapporo Medical University, School of Medicine, Department of Neuropsychiatry, Assistant, 医学部, 助手 (60315497)
KIKUCHI Seiji  Hokkaido University School of Medicine, Department of Neurology, Assistant Professor, 大学院・医学研究科, 講師 (10271660)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 2002: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2001: ¥8,700,000 (Direct Cost: ¥8,700,000)
KeywordsAdvanced glycation end-product / AGE-2 structure / Aβ (1-40) / AGE-2 derived Aβ (1-40) / Glycation / Alzheimer's disease / neurodegenerative diseases / 神経変性疾患 / Advanced Glycation End-product
Research Abstract

The Maillard reaction that leads to the formation of advanced glycation end-products (AGEs) plays an important role in the pathogenesis of angiopathy in diabetic patients, in aging and in neurodegenerative processes.
1) We developed anti-AGE antibodies that specifically recognize six distinct classes of AGE structures (AGE-1, glucose-derived AGEs, AGE-2, glyceraldehydes-derived AGEs ; AGE-3, glycolaldehyde-derived AGEs ; AGE-4, methylglyoxal- derived AGEs ; AGE-5, glyoxal-derived AGEs ; and AGE-6, 3-deoxyglucosone-derived AGEs) within the circulating proteins and peptides present in serum from diabetic patients on hemodialysis.
2) We recently reported that an elevation of serum AGE levels was found to be associated with severity of diabetic retinopathy. We also reported that AGEs in the serum of diabetic patients on hemodialysis have diverse biological activities on vascular wall, kidney mesangial and cortical neuronal cells. Therefore, these results suggest a causal role for these types … More of AGEs in the pathogenesis of diabetic complication and neurodegenerative disease.
3) Incubation of cortical neurons with six immunochemically distinct AGEs, designated AGEs-1 to -6, produced a dose-dependent increase in neuronal cell-death. The structural epitope designated AGE-2 (glyceraldehyde-derived AGEs) was found to have the greatest cytopathic effect and the neurotoxicity of AGE-2 was neutralized by the addition of an anti-AGE-2 specific antibody. We provide the first evidence for the toxicity of a specific AGE structure, defined as AGE-2, on rat primary cultured cortical neuronal cells.
4) The immunohistochemical study showed that AGE-2 existed in the Alzheimer's brain. The AGE-2 was mainly localized in the cytosol of neurons, not in the nucleus, astrocytes, and extracellular area. Senile plaques were not stained with the anti-AGE-2 antibody. There was no difference in neurotoxicity between AGE-2-Aβ and Aβ only. These results suggested that AGE-2 promotes neurotoxicity without reference to Aβ. We hypothesized that the AGE-2 immunopositive reaction in the pericaryon reflects the increase generation of AGE-2 in cytoplasm that occurs with the decline of GAPDH.
5) Recently, it has become clear that AGEs also have a role in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Creutzfeldt-Jakob disease, and amyotrophic lateral sclerosis (ALS). Less

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (122 results)

All Other

All Publications (122 results)

  • [Publications] 菊地誠志, 竹内正義, 佐々木信幸 他4名: "Glycation -A sweet tempter for neuronal death-"Brain Res. Review. 41. 306-323 (2003)

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  • [Publications] 竹内正義, 佐々木信幸, 菊地誠志他10名: "Neurotoxicity of acetaldehyde-derived advanced glycation end-products for cultured cortical neurons"J. Neuropathol. Exp. Neurol.. 62. 486-496 (2003)

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  • [Publications] 山岸昌一, 竹内正義, 佐々木信幸, 菊地誠志 他5名: "Angiotensin II-type 1 receptor interaction inhibits DNA synthesis and up-regulates vascular endothelial growth factor mRNA levels in retinal pericytes through intracellular reactive oxygen species generation"Drugs Exp. Clin. Res.. (印刷中). (2003)

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      2002 Final Research Report Summary
  • [Publications] 山岸昌一, 竹内正義 他3名: "Pigment epithelium-derived factor inhibits leptin-induced angiogenesis by suppressing vascular endothelial growth factor gene expression through anti-oxidative properties"Microvasc. Res.. 65. 186-190 (2003)

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  • [Publications] 三浦順之助, 竹内正義 他11名: "AGE downregulation of monocyte expression of RAGE mRNA and its association with diabetic complications in type 1 diabetes"J. Diabetes Complicat.. (印刷中). (2003)

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      2002 Final Research Report Summary
  • [Publications] 米倉秀人, 竹内正義 他11名: "Novel splice variants of the receptor for advanced glycation endproducts (RAGE) expressed in human vascular endothelial cells and pericytes, ad their putative roles in diabetes-induced vascular injury"Biochem. J.. 370. 1097-1109 (2003)

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  • [Publications] 菊地誠志, 竹内正義 他7名: "Effect of proteasome inhibitor on cultured mesencephalic dopaminergic neurons"Brain Res.. 964. 228-236 (2003)

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      2002 Final Research Report Summary
  • [Publications] 山岸昌一, 竹内正義 他3名: "Up-regulation of vascular endothelial growth factor and down-regulation of pigment epithelium-derived factor mRNA levels in leptin-exposed cultured retinal pericytes"Int. J. Tissue React.. 24. 137-142 (2003)

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  • [Publications] 稲垣洋介, 竹内正義 他3名: "Pigment epithelium-derived factor prevents advanced glycation end products-induced monocyte chemoattractant protein-1 production in microvascular endothelial cells by suppressing intracellular reactive oxygen species generation"Diabetologia. 46. 284-287 (2003)

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  • [Publications] 山岸昌一, 竹内正義 他4名: "Advanced glycation end products inhibit de novo protein synthesis and induce TGF-β overexpression in proximal tubular cells"Kidney Int.. 63. 464-473 (2003)

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  • [Publications] 山岸昌一, 竹内正義 他4名: "Dilazep hydrochloride, an antiplatelet drug, prevents progression of diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty rats"Drugs Exptl. Clin. Res.. 28. 221-227 (2003)

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      2002 Final Research Report Summary
  • [Publications] 三浦順之助, 竹内正義 他5名: "Serum leveles of non-carboxymethyllysine advanced glycation endproducts are correlated to severity of microvascular complications in patients with type 1 diabetes"J. Diabetes Complicat.. 27. 16-21 (2003)

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      2002 Final Research Report Summary
  • [Publications] 菊地誠志 他5名: "Brefeldin A-induced neurotoxicity in cultured spinal cord neurons"J. Neurosci. Res.. 71. 591-599 (2002)

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      2002 Final Research Report Summary
  • [Publications] 天野伸治郎, 竹内正義 他9名: "Sorbitol dehydrogenase overexpression potentiates glucose toxicity to cultured retinal pericytes"Biochem. Biophys. Res. Commun.. 299. 183-188 (2002)

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  • [Publications] 岡本珠美, 竹内正義 他7名: "Angiogenesis induced by advanced glycation end products and its prevention by cerivastatin"FASEB J.. 26. 1928-1930 (2002)

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  • [Publications] Petrova R, 竹内正義 他12名: "Advanced glycation endproduct-induced calcium handling impairment in mouse cardiac myocytes"J. MoL Cell. Cardiol.. 34. 1425-1431 (2002)

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  • [Publications] 古賀康八郎, 竹内正義 他7名: "CS-866, a New angiotensin II type 1 receptor antagonist, Ameliorates glomerular anionic site loss and prevents progression of diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty rats"Mol. Med.. 8. 591-599 (2002)

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  • [Publications] 菊地誠志, 竹内正義 他5名: "Detection of N-(carboxymethyl)lysine (CML) and non-CML advanced glycation end products in the anterior horn of amyotrophic lateral sclerosis spinal cord"Amyotroph. Lateral Scler. Other Motor Neuron Disord.. 3. 63-68 (2002)

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  • [Publications] 山岸昌一, 竹内正義 他4名: "Beraprost sodium, a prostaglandin I_2 analogue, protects against advanced glycation end products-induced injury in cultured retinal pericytes"Mol. Med.. 8. 546-550 (2002)

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  • [Publications] 三好秀明, 竹内正義 他7名: "Aminoguanidine pyridoxal adduct is superior to aminoguanidine for preventing diabetic nephropathy in mice"Horm. Metab. Res.. 34. 371-377 (2002)

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  • [Publications] 岡本珠美, 竹内正義, 菊地誠志 他5名: "Incadronate disodium inhibits advanced glycation end products-induced angiogenesis in vivo"Biochem. Biophys. Res. Commun.. 297. 419-424 (2002)

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      2002 Final Research Report Summary
  • [Publications] 菊地誠志, 竹内正義 他5名: "Effect of geranylgeranylaceton on cellular damage induced by proteasome inhibition in cultured spinal neuro"J. Neurosci. Res.. 69. 373-381 (2002)

    • Description
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    • Related Report
      2002 Final Research Report Summary
  • [Publications] 山岸昌一, 竹内正義 他4名: "Pigment epithelium-derived factor protects cultured retinal pericytes from advanced glycation end product-induced injury through its anti-oxidative properties"Biochem. Biophys. Res. Commun.. 296. 877-882 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 古賀康八郎, 竹内正義 他5名: "Serum levels of glucose-derived advanced glycation end products are associated with the severity of diabetic retinopathy in type 2 diabetic patients without renal dysfunction"Int. J. Clin. Pharm. Res.. 22. 23-27 (2002)

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      2002 Final Research Report Summary
  • [Publications] 佐々木信幸, 竹内正義, 菊地誠志 他8名: "Advanced glycation end products (AGE) and their receptor (RAGE) in the brain of patients with Creutzfeldt-Jakob disease with prion plaques"Neurosci. Lett.. 326. 117-120 (2002)

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      2002 Final Research Report Summary
  • [Publications] 山岸昌一, 佐々木信幸, 菊地誠志, 竹内正義 他6名: "Palmitate-induced apoptosis of microvascular endothelial cells and pericytes"Mol. Med.. 8. 179-184 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 山岸昌一, 竹内正義 他5名: "Advanced glycation end products-induced apoptosis and overexpression of vascular endothelial growth factor and monocyte chemoattractant protein-1 in human cultured mesangial cells"J. Biol. Chem.. 277. 20309-20315 (2002)

    • Description
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      2002 Final Research Report Summary
  • [Publications] 山岸昌一, 竹内正義 他7名: "Advanced glycation end products-induced apoptosis and overexpression of vascular endothelial growth factor in bovine retinal pericytes"Biochem. Biophys. Res. Commun.. 290. 973-978 (2002)

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      2002 Final Research Report Summary
  • [Publications] 菊地誠志 他2名: "Prostaglandin E1 protects cultured spinal neurons against the effects of nitric oxide toxicity"Neuropharmacology. 42. 714-723 (2002)

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  • [Publications] 竹内正義 他6名: "Immunological detection of a novel advanced glycation end-product"Mol. Med.. 7. 783-791 (2001)

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  • [Publications] 山岸昌一, 竹内正義, 牧田善二: "Advanced glycation end products and the pathogenesis of diabetic nephropathy"Contrib. Nephrol.. 134. 30-35 (2001)

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  • [Publications] 山本靖彦, 竹内正義 他10名: "Development and prevention of advanced diabetic nephropathy in RAGE-overexpressing mice"J. Clin. Invest.. 108. 261-268 (2001)

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  • [Publications] 遠藤美紀子, 竹内正義 他8名: "Increased levels of vascular endothelial growth factor and advanced glycation end products in aqueous humor of patients with diabetic retinopathy"Horm. Metab. Res.. 33. 317-322 (2001)

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  • [Publications] 和田龍一, 竹内正義 他6名: "Effect of OPB-9195, anti-glycation agent, on experimental diabetic neuropathy"Eur, J. Clin, Invest.. 31. 513-520 (2001)

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  • [Publications] 竹内正義, 牧田善二: "Alternative routes for the formation of immunochemically distinct advanced glycation end-products in vivo"Curr. Mol. Med.. 1. 305-315 (2001)

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  • [Publications] 佐々木信幸, 竹内正義 他6名: "Immunohistochemical distribution of the receptor for advanced glycation end products in neurons and astrocytes in Alzheimer's disease"Brain Res.. 888. 256-262 (2001)

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  • [Publications] 竹内正義, 山岸昌一, 山本博: "BIO Clinica 6月臨時増刊号、18巻7号"高血糖とAGE:新しい治療戦略. 5 (2003)

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  • [Publications] 竹内正義, 山岸昌一, 牧田善二: "日本臨床増刊号:新時代の糖尿病学(3)-病因・診断・治療研究の進歩60巻増刊号9"糖尿病治療学の進歩V.2型糖尿病治療の実際(3)糖尿病合併症治療薬:AGE阻害薬OPB-9195. 5 (2002)

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  • [Publications] 渡辺琢夫, 竹内正義 他4名: "Diabetes Frontier 13巻2号"特集:糖尿病と酸化ストレス-高血糖による細胞内酸化ストレス増強機序:終末糖化産物-. 5 (2002)

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  • [Publications] 柳瀬由紀子, 竹内正義: "Medical Technology:わだい 「生体内AGE産生過程と神経細胞毒性」"医歯薬出版. 2 (2001)

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  • [Publications] 山岸昌一, 牧田善二, 竹内正義: "内科、特集:最近注目されてきた疾患、病態、治療 「糖尿病腎症の発症機構とその治療」"南江堂. 4 (2001)

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  • [Publications] 菊地誠志, 竹内正義 他5名: "In molecular mechanism and therapeutics of amyotrophic lateral sclerosis : Abnormal glycation in ALS"Elservier Science (Amsterdam). 9 (2001)

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  • [Publications] 新保和賢, 菊地誠志 他4名: "In molecular mechanism and therapeutics of amyotrophic lateral sclerosis : ROS/RNS dicarbonyl stress to spinal motor neurons in vitro"Elservier Science (Amsterdam). 7 (2001)

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  • [Publications] Takeuchi M and Makita Z: "Alternative routes for the formation of immunochemically distinct advanced glycation end-products in vivo"Curr. Mol. Med.. 1. 305-315 (2001)

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  • [Publications] Kikuchi S, Shinpo K, Takeuchi M, Yamagishi S, Makita Z, Sasaki N, and Tashiro K: "Glycation-a sweet tempter for neuronal death"Brain Res. Brain Res. Rev.. 41. 306-323 (2003)

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      2002 Final Research Report Summary
  • [Publications] Yamagishi S, Takeuchi M and Makita Z: "Advanced glycation end products and the pathogenesis of diabetic nephripathy"Contrib. Nephrol.. 134. 30-35 (2001)

    • Description
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    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sasaki N, Toki S, Choei H, Saito T, Nakano N, Hayashi Y, Takeuchi M, and Makita Z: "Immunohistochemical distribution of the receptor for advanced glycation end products in neurons and astrocytes in Alzheimer's disease"Brain Res.. 888. 256-262 (2001)

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      2002 Final Research Report Summary
  • [Publications] Endo M, Yanagisawa K, Tuchida K, Okamoto T, Matsushita T, Higuchi M, Takeuchi M, Makita Z, and Koike T: "Increased levels of vascular endothelial growth factor and advanced glycation end products in aqueous humor of patients with diabetic retinopathy"Horm. Metab. Res.. 33. 317-322 (2001)

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      2002 Final Research Report Summary
  • [Publications] Wada R, Nishizawa Y, Yagihashi N, Takeuchi M, Ishikawa Y, Yasumura K, Nakano M, and Yagihashi S: "Effect of OPB-9195, anti-glycation agent, on experimental diabetic neuropathy"Eur. J. Clin. Invest.. 31. 513-520 (2001)

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      2002 Final Research Report Summary
  • [Publications] Yamamoto Y, Kato I, Doi T, Yonekura H, Ohashi S, Takeuchi M, Watanabe T, Yamagishi S, Sakurai S, Takasawa S, Okamoto H, and Yamamoto H: "Development and prevention of advanced diabetic nephropathy in RAGE-overexpressing mice"J. Clin. Invest.. 108. 261-268 (2001)

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      2002 Final Research Report Summary
  • [Publications] Takeuchi M, Yanase Y, Matsuura N, Yamagishi S, Kameda Y, Bucala R, and Makita Z: "Immunological detection of a novel advanced glycation end-product"Mol. Med.. 7. 783-791 (2001)

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      2002 Final Research Report Summary
  • [Publications] Yamagishi S, Takeuchi M, and Unoki H: "Can we identify genes for susceptibility to diabetic microangiopathies using stroke-prone spontaneously hypertensive rat models?"Med. Hypotheses. 56. 510-512 (2001)

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  • [Publications] Yamagishi S-I, Amano S, Inagaki Y, Okamoto T, Koga K, Sasaki N, Yamamoto H, Takeuchi M, and Makita Z: "Advanced glycation end products-induced apoptosis and overexpression of vascular endothelial growth factor in bovine retinal pericytes"Biochem. Biophys. Res. Commun.. 290. 973-978 (2002)

    • Description
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    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamagishi S-I, Inagaki Y, Okamoto T, Amano S, Koga K, Takeuchi M, and Makita Z: "Advanced glycation end products-induced apoptosis and overexpression of vascular endothelial growth factor and monocyte chemoattractant protein-1 in human cultured mesangial cells."J. Biol. Chem.. 277. 20309-20315 (2002)

    • Description
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    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamagishi S-I, Okamoto T, Amano S, Inagaki Y, Koga K, Choei H, Sasaki N, Kikuchi S, Takeuchi M, and Makita Z: "Palmitate-induced apoptosis of microvascular endothelial cells and pericytes"Mol. Med.. 8. 179-184 (2002)

    • Description
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    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sasaki N, Takeuchi M, Choei H, Kikuchi S, Hayashi Y, Nakano N, Ikeda H, Yamagishi S-I, Kitamoto T, Saito T, and Makita Z: "Advanced glycation end products (AGE) and their receptor (RAGE) in the brain of patients with Creutzfeldt-Jakob disease with prion plaques"Neurosci. Lett.. 326. 117-120 (2002)

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    • Related Report
      2002 Final Research Report Summary
  • [Publications] Koga K, Yamagishi S, Okamoto T, Inagaki Y, Amano S, Takeuchi M, and Makita Z: "Serum levels of glucose-derived advanced glycation end products are associated with the severity of diabetic retinopathy in type 2 diabetic patients without renal dysfunction."Int. J. Clin. Pharm. Res.. 22. 23-27 (2002)

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      2002 Final Research Report Summary
  • [Publications] Yamagishi S-I, Inagaki Y, Amano S, Okamoto T, Takeuchi M, and Makita Z: "Pigment epithelium-derived factor protects cultured retinal pericytes from advanced glycation end product-induced injury through its anti-oxidative properties"Biochem. Biophys. Res. Commun.. 296. 877-882 (2002)

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    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kikuchi S, Shinpo K, Takeuchi M, Tsuji S, Yabe I, Niino M, and Tashiro K: "Effect of geranylgeranylaceton on cellular damage induced by proteasome inhibition in cultured spinal neurons"J. Neurosci. Res.. 69. 373-381 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okamoto T, Yamagishi S-I, Inagaki Y, Amano S, Takeuchi M, Kikuchi S, Ohno S, and Yoshimura A: "Incadronate disodium inhibits advanced glycation end products-induced angiogenesis in vitro"Biochem. Biophys. Res. Commun.. 297. 419-424 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyoshi H, Taguchi T, Sugiura M, Takeuchi M, Yanagisawa K, Watanabe Y, Miwa I, Makita Z, and Koike T: "Aminoguanidine pyridoxal adduct is superior to aminoguanidine for preventing diabetic nephropathy in mice"Horm. Metab. Res.. 34. 371-377 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamagishi S-I, Amano S, Inagaki Y, Okamoto T, Takeuchi M, and Makita Z: "Beraprost sodium, a prostaglandin I_2 analogue, protects against advanced glycation end products-induced injury in cultured retinal pericytes"Mol. Med.. 8. 546-550 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kikuchi S, Shinpo K, Ogata A, Tsuji S, Takeuchi M, Makita Z, and Tashiro K: "Detection of N-(carboxymethyl)lysine (CML) and non-CML advanced glycation end products in the anterior horn of amyotrophic lateral sclerosis spinal cord"Amyotroph. Lateral Scler. Other Motor Neuron Disord.. 3. 63-68 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Koga K, Yamagishi S-I, Takeuchi M, Inagaki Y, Amano S, Okamoto T, Saga T, Makita Z, and Yoshizuka M: "CS-866, a New angiotensin II type 1 receptor antagonist, ameliorates glomerular anionic site loss and prevents progression of diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty rats."Mol. Med.. 8. 591-599 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Petrova R, Yamamoto Y, Muraki K, Yonekura H, Sakurai S, Watanabe T, Li H, Takeuchi M, Makita Z, Kato I, Takasawa S, Okamoto H, Imaizumi Y, and Yamamoto H: "Advanced glycation endproduct-induced calcium handling impairment in mouse cardiac myocytes"J. Mol. Cell. Cardiol.. 34. 1425-1431 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okamoto T, Yamagishi S-I, Inagaki Y, Amano S, Koga K, Abe R, Takeuchi M, Ohno S, Yoshimura A, and Makita Z: "Angiogenesis induced by advanced glycation end products and its prevention by cerivastatin"FASEB J.. 16. 1928-1930 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Amano S, Yamagishi S-I, Kato N, Inagaki Y, Okamoto T, Koga K, Makino M, Taniko K, Hirooka H, Jomori T, and Takeuchi M: "Sorbitol dehydrogenase overexpiession potentiates glucose toxicity to cultured retinal pericytes"Biochem. Biophys. Res. Commun.. 299. 183-188 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kikuchi S, Shinpo K, and Tashiro K: "Prostaglandin E1 protects cultured spinal neurons against the effects of nitric oxide toxicity"Neuropharmacology. 42. 714-723 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miura J, Yamagishi S-I, Uchigata Y, Takeuchi M, Yamamoto H, Makita Z, and Iwamoto Y: "Serum leveles of non-carboxymethyllysine advanced glycation endproducts are correlated to severity of microvascular complications in patients with type 1 diabetes"J. Diabetes Complicat.. 17. 16-21 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamagishi S-I, Koga K, Inagaki Y, Amano S, Okamoto T, and Takeuchi M: "Dilazep hydrochloride, an antiplatelet drug, prevents progression of diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty rats"Drugs Exptl. Clin. Res.. 28. 221-227 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamagishi S-I, Inagaki Y, Okamoto T, Amano S, Koga K, and Takeuchi M: "Advanced glycation end products inhibit de novo protein synthesis and induce TGF-β overexpression in proximal tubular cells"Kidney Int.. 63. 464-473 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Inagaki Y, Yamagishi S-I, Okamoto T, Takeuchi M, and Amano S: "Pigment epithelium-derived factor prevents advanced glycation end products-induced monocyte chemoattractant protein-1 production in microvascular endothelial cells by suppressing intracellular reactive oxygen species generation."Diabetologia. 46. 284-287 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamagishi S, Inagaki Y, Amano S, Okamoto T, and Takeuchi M: "Up-regulation of vascular endothelial growth factor and down-regulation of pigment epithelium-derived factor messenger ribonucleic acid levels in leptin-exposed cultured retinal pericytes."Int. J. Tissue React.. 24. 137-142 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kikuchi S, Shinpo K, Tsuji S, Takeuchi M, Yamagishi S, Makita Z, Niino M, Yabe I, and Tashiro K: "Effect of proteasome inhibitor on cultured mesencephalic dopaminergic neurons"Brain Res.. 964. 228-236 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yonekura H, Yamamoto Y, Sakurai S, Petrova RG, Abedin MJ, Li H, Yasui K, Takeuchi M, Makita Z, Takasawa S, Okamoto H, Watanabe T, and Yamamoto H: "Novel splice variants of the receptor for advanced glycation endproducts (RAGE) expressed in human vascular endothelial cells and pericytes, and their putative roles in diabetes-induced vascular injury."Biochem. J.. 370. 1097-1109 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miura J, Uchigata Y, Yamamoto Y, Takeuchi M, Sakurai S, Watanabe T, Yonekura H, Yamagishi S-I, Makita Z, Sato A, Omori Y, Yamamoto H, and Iwamoto Y: "AGE downregulation of monocyte expression of RAGE mRNA and its association with diabetic complications in type 1 diabetes"J. Diabetes Complicat.. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamagishi S, Amano S, Inagaki Y, Okamoto T, Takeuchi M, and Inoue H: "Pigment epithelium-derived factor inhibits leptin-induced angiogenesis by suppressing vascular endothelial growth factor gene expression through anti-oxidative properties"Microvasc. Res.. 65. 186-190 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamagishi S, Amano S, Inagaki Y, Okamoto T, Inoue H, Takeuchi M, Choei H, Sasaki N, and Kikuchi S: "Angiotensin II-type 1 receptor interaction inhibits DNA synthesis and up-regulates vascular endothelial growth factor mRNA levels in retinal pericytes through intracellular reactive oxygen species generation."Drugs Exp. Clin. Res.. (in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takeuchi M, Watai T, Sasaki N, Choei H, Iwaki M, Ashizawa T, Inagaki Y, Yamagishi S, Kikuchi S, Riederer P, Saito T, Bucala R, and Kameda Y: "Neurotoxicity of acetaldehyde-derived advanced glycation end-products for cultured cortical neurons"J. Neuropathol. Exp. Neurol.. 62. 486-496 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kikuchi S, Shinpo K, Tsuji S, Yabe I, Niino M, and Tashiro K: "Brefeldin A-induced neurotoxicity in cultured spinal cord neurons"J. Neurosci. Res.. 71. 591-599 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 菊地誠志, 竹内正義, 佐々木信幸 他4名: "Glycation-A sweet tempter for neuronal death-"Brain Res.Review. (印刷中). (2003)

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      2002 Annual Research Report
  • [Publications] 竹内正義, 佐々木信幸, 菊地誠志 他10名: "Neurotoxicity of acetaldehyde-derived advanced glycation end-products for cultured cortical neurons"J.Neuropathol.Exp.Neurol.. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 山岸昌一, 竹内正義, 佐々木信幸, 菊地誠志 他5名: "Angiotensin II-type 1 receptor interaction inhibits DNA synthesis and up-regulates vascular endothelial growth factor mRNA levels in retinal pericytes through intracellular reactive oxygen species generation"Drugs Exp.Clin.Res.. (印刷中). (2003)

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      2002 Annual Research Report
  • [Publications] 山岸昌一, 竹内正義 他3名: "Leptin stimulates proliferation of microvascular endothelial cells through autocrine vascular endothelial wth factor production-a possible participation of reactive oxygen species in leptin-induced angiogenesis-"Microvas.Res.. (印刷中). (2003)

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      2002 Annual Research Report
  • [Publications] 三浦順之助, 竹内正義 他11名: "AGE downregulation of monocyte expression of RAGE mRNA and its association with diabetic complications in type 1 diabetes"J.Diabetes Complicat.. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 米倉秀人, 竹内正義 他11名: "Novel splice variants of the receptor for advanced glycation endproducts (RAGE) expressed in human vascular endothelial cells and pericytes, ad their putative roles in diabetes-induced vascular injury"Biochem.J.. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 菊地誠志, 竹内正義 他7名: "Effect of proteasome inhibitor on cultured mesencephalic dopaminergic neurons"Brain Res.. 964. 228-236 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 山岸昌一, 竹内正義 他3名: "Leptin up-regulates vascular endothelial growth factor and down-regulates pigment epithelium-derived factor mRNA levels in cultured retinal pericytes"Int.J.Tissue React.. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 稲垣洋介, 竹内正義 他3名: "Pigment epithelium-derived factor prevents advanced glycation end products-induced monocyte chemoattractant protein-1 production in microvascular endothelial cells by suppressing intracellular reactive oxygen species generation"Diabetologia. 46. 284-287 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 山岸昌一, 竹内正義 他4名: "Advanced glycation end products inhibit de novo protein synthesis and induce TGF-β overexpression in proximal tubular cells"Kidney Int.. 63. 464-473 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 山岸昌一, 竹内正義 他4名: "Dilazep hydrochloride, an antiplatelet drug, prevents progression of diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty rats"Drugs Exp.Clin.Res.. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 三浦順之助, 竹内正義 他5名: "Serum leveles of non-carboxymethyllysine advanced glycation endproducts are correlated to severity of microvascular complications in patients with type 1 diabetes"J.Diabetes Complicat.. 17. 16-21 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 天野伸治郎, 竹内正義 他9名: "Sorbitol dehydrogenase overexpression potentiates glucose toxicity to cultured retinal pericytes"Biochem.Biophys.Res.Commun.. 299. 183-188 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 岡本珠美, 竹内正義 他7名: "Angiogenesis induced by advanced glycation end products and its prevention by cerivastatin"FASEB J.. 16. 1928-1930 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Petrova R, 竹内正義 他12名: "Advanced glycation endproduct-induced calcium handling impairment in mouse cardiac myocytes"J.Mol.Cell.Cardiol.. 34. 1425-1431 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 古賀康八郎, 竹内正義 他7名: "CS-866, a New angiotensin II type 1 receptor antagonist, Ameliorates glomerular anionic site loss and prevents progression of diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty rats"Mol.Med.. 8. 591-599 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 菊地誠志, 竹内正義 他5名: "Detection of N-(carboxymethyl)lysine (CML) and non-CML advanced glycation end products in the anterior horn of amyotrophic lateral sclerosis spinal cord"Amyotroph.Lateral Scler.Other Motor Neuron Disord.. 3. 63-68 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 山岸昌一, 竹内正義 他4名: "Beraprost sodium, a prostaglandin I_2 analogue, protects against advanced glycation end products-induced injury in cultured retinal pericytes"Mol.Med.. 8. 546-550 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 三好秀明, 竹内正義 他7名: "Aminoguanidine pyridoxal adduct is superior to aminoguanidine for preventing diabetic nephropathy in mice"Horm.Metab.Res.. 34. 371-377 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 岡本珠美, 竹内正義, 菊地誠志 他5名: "Incadronate disodium inhibits advanced glycation end products-induced angiogenesis in vivo"Biochem.Biophys.Res.Commun.. 297. 419-424 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 菊地誠志, 竹内正義 他5名: "Effect of geranylgeranylaceton on cellular damage induced by proteasome inhibition in cultured spinal neuro"J.Neurosci.Res.. 69. 373-381 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 山岸昌一, 竹内正義 他4名: "Pigment epithelium-derived factor protects cultured retinal pericytes from advanced glycation end product-induced injury through its anti-oxidative properties"Biochem.Biophys.Res.Commun.. 296. 877-882 (2002)

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      2002 Annual Research Report
  • [Publications] 古賀康八郎, 竹内正義 他5名: "Serum levels of glucose-derived advanced glycation end products are associated with the severity of diabetic retinopathy in type 2 diabetic patients without renal dysfunction"Int.J.Clin.Pharm.Res.. 22. 23-27 (2002)

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  • [Publications] 佐々木信幸, 竹内正義, 菊地誠志 他8名: "Advanced glycation end products (AGE) and their receptor (RAGE) in the brain of patients with Creutzfeldt-Jakob disease with prion plaques"Neurosci.Lett.. 326. 117-120 (2002)

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  • [Publications] 山岸昌一, 佐々木信幸, 菊地誠志, 竹内正義 他6名: "Palmitate-induced apoptosis of microvascular endothelial cells and pericytes"Mol.Med.. 8. 179-184 (2002)

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  • [Publications] 山岸昌一, 竹内正義 他5名: "Advanced glycation end product-induced apoptosis and overexpression of vascular endothelial growth factor and monocyte chemoattractant protein-1 in human-cultured mesangial cells"J.Biol.Chem.. 277. 20309-20315 (2002)

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  • [Publications] 竹内正義, 山岸昌一, 山本博: "高血糖とAGE:新しい治療戦略"BIO Clinica 6月臨時増刊号. 18巻7号. 5 (2003)

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  • [Publications] 竹内正義, 山岸昌一, 牧田善二: "糖尿病治療学の進歩V.2型糖尿病治療の実際(3)糖尿病合併症治療薬:AGE阻害薬OPB-9195"日本臨床増刊号:新時代の糖尿病学(3)-病因・診断・治療研究の進歩. 60巻増刊号9. 5 (2002)

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  • [Publications] 渡辺琢夫, 竹内正義 他4名: "特集:糖尿病と酸化ストレス 高血糖による細胞内酸化ストレス増強機序:終末糖化産物"Diabetes Frontier. 13巻2号. 5 (2002)

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  • [Publications] 山岸昌一, 竹内正義 他7名: "Advanced glycation end products-induced apoptosis and overexpression of vascular endothelial growth factor in bovine retinal pericytes"Biochem. Biophys. Res. Commun.. 290(3). 973-978 (2002)

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  • [Publications] 竹内正義 他6名: "Immunological detection of a novel advanced glycation end-product"Mol. Med.. 7(11). 783-791 (2001)

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  • [Publications] 山岸昌一, 竹内正義, 牧田善二: "Advanced glycation end products and the pathogenesis of diabetic nephropathy"Contrib. Neplirol. 134. 30-35 (2001)

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      2001 Annual Research Report
  • [Publications] 山本靖彦, 竹内正義 他10名: "Development and prevention of advanced diabetic nephropathy in RAGE-overexpressing mice"J. Clin. Invest.. 108(2). 261-268 (2001)

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      2001 Annual Research Report
  • [Publications] 遠藤美紀子, 竹内正義 他8名: "Increased levels of vascular endothelial growth factor and advanced glycation end products in aqueous humor of patients with diabetic retinopathy"Horm. Metab. Res.. 33(5). 317-322 (2001)

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      2001 Annual Research Report
  • [Publications] 和田龍一, 竹内正義 他6名: "Effect of OPB-9195, anti-glycation agent, on experimental diabetic neuropathy"Eur. J. Clin. Invest.. 31(6). 513-520 (2001)

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  • [Publications] 竹内正義, 牧田善二: "Alternative routes for the formation of immunochemically distinct advanced glycation end-products in vivo"Curr. Mol. Med.. 1(3). 305-315 (2001)

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      2001 Annual Research Report
  • [Publications] 菊地誠志 他2名: "Prostaglandin El protects cultured spinal neurons against the effects of nitric oxide toxicity"Neuropharmacology. (印刷中). (2002)

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      2001 Annual Research Report
  • [Publications] 佐々木信幸, 竹内正義 他6名: "Immunohistochemical distribution of the receptor for advanced glycation end products in neurons and astrocytes in Alzheimer's disease"Brain Res.. 888(2). 256-262 (2001)

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  • [Publications] 柳瀬由紀子, 竹内正義: "Medical Technology:わだい「生体内AGE産生過程と神経細胞毒性」"医歯薬出版. 2 (2001)

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      2001 Annual Research Report
  • [Publications] 山岸昌一, 牧田善二, 竹内正義: "内科、特集:最近注目されてきた疾患、病態、治療「糖尿病腎症の発症機構とその治療」"南江堂. 4 (2001)

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  • [Publications] 菊地誠志, 竹内正義 他5名: "In molecular mechanism and therapeutics of amyotrophic lateral sclerosis : 「Abnormal glycation in ALS」"Elservier Science(Amsterdam). 9 (2001)

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  • [Publications] 新保和賢, 菊地誠志 他4名: "In molecular mechanism and therapeutics of amyotrophic lateral sclerosis : 「ROS/RNS dicarbonyl stress to spinal motor neurons in vitro」"Elservier Science(Amsterdam). 7 (2001)

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Published: 2001-04-01   Modified: 2016-04-21  

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