1998 Fiscal Year Annual Research Report

腎疾患における高度糖化蛋白の病態生理学的意義に関する共同研究

Research Project

Project/Area Number	09044280
Research Institution	Tokai University
Principal Investigator	宮田敏男東海大学, 総合医学研究所, 講師 (10222332)
Co-Investigator(Kenkyū-buntansha)	DE Strihou C ルバイン大学, 医学部, 教授 BAYNES John サウスカロライナ大学, 医学部, 教授 DAIVID Stern コロンビア大学, 細胞生理学部, 教授 MONNIER Vinc ケースウエスタンリザーブ大学, 病理研究所, 教授
Keywords	酸化ストレス / カルボニルストレス / AGEs / 腎不全 / レドックス制御 / 糖尿病 / ペントシジン
Research Abstract	病変部での反応性力ルボニル及びその蛋白修飾物の同定・定量及びその形成・反応性経路の解明腎不全患者血中に存在するカルボニルをHPLC及びマススペクトメトリーを用いて腎不全患者血中のAGEs解析を行い、carboxymethyllysine(CML)及びpentosidineがアルブミン分画を中心に存在することを明らかにし、さらに正確な生化学的定量法を確立した。組織蛋白については深刻な長期透析合併症である透析アミロイドーシスのアミロイド中にAGEsが存在することを生化学的及び免疫組織学的に明らかにし、さらに個々の構造体としてもCMLとpentosidineの存在を明らかにした。抗体については、pentosidineに対する特異的なpolyclonal抗体及び主にCMLを認識するPolyclonalなAGEs抗体も作製した。カルボニル及びその蛋白修飾物の病態生理学的意義の解析カルボニルについては神経細胞をカルボニルであるglyoxal存在下で培養し、神経細胞にカルボニル蛋白修飾物最終産物であるCMLが精製されることを明らかにした。カルボニル蛋白修飾物については、各種細胞をAGEs存在下で培養し、単球マクロファージからのサイト力イン(IL-1b,lL-6,TNF-)産生促進作用、血管内皮細胞の増殖及び^3H-thymidine取り込み促進作用、骨芽・破骨細胞を含んだ全骨培養系での骨吸収促進を明らかにした。

Research Products

(47 results)

All Other

All Publications (47 results)

[Publications] Toshio Miyata: "Funcional quantiative analysis of the genome in cultured human mesangial cells." Kidney International. 53. 154-158 (1998)
[Publications] Toshio Miyata: "Renal catabolism of advanced glycation end products:the fate of pentosidne." Kidney International. 53. 416-422 (1998)
[Publications] Toshio Miyata: "Increased pentosidine,an davanced glycation end products,in plasma and synovial fluid from patients with rheumatoid arthritis and its relation with markers of inflammation." Biochem Biophys Res Commun. 244. 45-49 (1998)
[Publications] Toshio Miyata: "Stress carbonyle et complications a long terme de I uremie" ACTUALITES NEPHROLOGIQUES JEAN HAMBURGER.Ho^^<^>PITAL NECKER 1998. 247-253
[Publications] Toshio Miyata: "Protein-bound acrolein:potential markers for oxidative stress." Proc Natl Acad Sci USA. 95. 4882-4887 (1998)
[Publications] Toshio Miyata: "Alteraitions of synovial tissue and their potential rolu in the deposition of β_2-microglobulin-associated amyloid." Nephrol Dial Transplant. 13. 1465-1475 (1998)
[Publications] Toshio Miyata: "β2-Microgloburin in renal disease." J Am Soc Nephrol. 9. 1723-1735 (1998)
[Publications] Toshio Miyata: "Implication of the glycoxidation and lipoxidation rections in the pathogenesis of dialysis-related amyloidosis." Int J Mol Med. 2. 561-565 (1998)
[Publications] Toshio Miyata: "Plasma level of pentosidine in diabetic patients:an advanced glycation end product." J Am Soc Nephrol. 9. 1681-1688 (1998)
[Publications] Toshio Miyata: "Implication of altered redox regulation by antioxidant enzymes in the increased plasma pentosidine,an advanced glycation end product,in uremia." Biochem Biophys Res Commun. 245. 785-790 (1998)
[Publications] Toshio Miyata: "Autoxidation products of both carbohydrates and lipids are increased in uremic plasma:Is there oxidative stress in uremia?" Kidney International. 54. 1290-1295 (1998)
[Publications] Toshio Miyata: "A mesangium-predominant gene,megsin,is a new serpin up-regulated in lgA nephropathy." J Clin Invest. 102. 828-836 (1998)
[Publications] Toshio Miyata: "Accelerated formation of carboxymethyllysine,an advanced glycation end product,by glyoxal and 3-deoxyglucosone in cultured ratsensoryneurons" Biochem Biophys Res Commun. 248. 93-97 (1998)
[Publications] Toshio Miyata: "Advanced glycation end products co-localization with astoricytes and microglial cells in Alzheimer's disease brain." Acta Neuropathol. 98. 555-558 (1998)
[Publications] Toshio Miyata: "Generation of protein carbonyls by glycation and lipoxidation reactions with autoxidation products of ascorbic acid and polyunsaturated fatty acids." FEBS letter. 437. 24-28 (1998)
[Publications] Toshio Miyata: "Localization of identified advanced glycation end product structure-carboxymethyllysine and pentosidine,in age-related inclusions in humanbrains" Pathology International. 48. 575-579 (1998)
[Publications] Toshio Miyata: "Level of HgCl_2-meditated phosphorylaiton of intracellular proteins determines death of thymic T-lymphocytes with or without DNA fragmentation." J Cellular Biochemistry. 71. 243-253 (1998)
[Publications] Toshio Miyata: "Carbonyl stress in uremia:Accumulation of carbonyls accelerate the formation of pentosidine,an advanced glycation end product." J Am Soc Nephrol. 9. 2349-2356 (1998)
[Publications] Toshio Miyata: "Carbonyl compounds cross-link cellular proteins and activate protein-tyrosine kinase p60_<c-src>" J Cellular Biochemistry. 72. 1-7 (1998)
[Publications] Toshio Miyata: "Alterations in non-enzymatic biochemistry in uremia:Origin and significance of ″carbonyl stress″in long-term uremic complications." Kidney International. 55. 389-399 (1998)
[Publications] Toshio Miyata: "Carbonyl stress:increased carbonyl modification of proteins by autoxidation products of carbohydrates and lipids." Int J Art Org. (in press).
[Publications] Toshio Miyata: "Possible involvement of ″carbonyl stress″ in the pathogenesis of dialysis-related amyloidosis." Am J Med Sci. (in press).
[Publications] Toshio Miyata: "Rapid formation of advanced glycation end products following vascular injury in euglycemic rat carotid artery:Role of oxidative stress." Circulation Research. (in press).
[Publications] Toshio Miyata: "Oxidative stress-induced ″carbonyl stress″ in uremia." Redox Regulation Clinical Application. (in press).
[Publications] Toshio Miyata: "″Carbonyl Stress″ and long-term uremic complications." Advanced in Nephrology. (in press).
[Publications] Toshio Miyata: "Carbonyl stress in long-term uremic complications." Nephrol Dial Transplant. (in press).
[Publications] Toshio Miyata: "″Carbonyl Stress″ and dialysis-related amyloidosis." Dial Transplant. (in press).
[Publications] Toshio Miyata: "Immunohistochemical evidence for an increased oxidative stress and carbonyl modification of proteins by autoxidation products of carbohydrates,lipids,and amino acids in diabetic glomerular lesions." J Am Soc Nephrol. (in press).
[Publications] Toshio Miyata: "Carbonyl stress:Increased carbonyl modification of tissue and cellular proteins in uremia." Peritoneal Dialysis international. (in press).
[Publications] Toshio Miyata: "β2-microglobulin and renal bone disease." Peritoneal Dialysis International. (in press).
[Publications] Toshio Miyata: "A sensitive and specific ELISA for plasma pentosidine." Nephrol Dial Transplant. (in press).
[Publications] Toshio Miyata: "Neurotoxicity of methylglyxal and 3-Deoxyglycose on cultured cortical-neurons:Synergism between glycation and oxidative stress,possibly involved in neurodegnerative diseases." Neurosci letter. (in press).
[Publications] Toshio Miyata: "Development of a polyclonal antibody with broad epitope specificityy for advancedglycation end products and its use for the detection of AGEs in again human Bruch's membrane and choroid." Experimental Eye Research. (in press).
[Publications] Toshio Miyata: "Infuluence of hemodialysis membrane type on pentosidine plasma level,a marker of ″carbonyl stress″." Kidney International. (in press).
[Publications] Toshio Miyata: "Carbonyl stress and diabetic nephropathy." Jpn J Nephrol. (in press).
[Publications] Toshio Miyata: "Implication of carbonyl stress in long-term uremic complications." Blood Purification. (in press).
[Publications] Toshio Miyata: "Advanced glycation end products potentiate human platelet aggregation in vitrα Possible role of oxidative stress." Biochem Biophys Res Commun. (in press).
[Publications] Toshio Miyata: "The first Japan-European Nephrology Forum." Nephrol Dial Transplant. (in press).
[Publications] Toshio Miyata: "Increased carbonyl modification of proteins by lipids and carbohydrates in diabetic nephropathy." Kidney International. (in press).
[Publications] Toshio Miyata: "Increase of the advanced glycation endproduct pentosidine in Bruchs membrane with age." Investigative Ophthalmology Visual Science. (in press).
[Publications] Toshio Miyata: "Expression of megsin mRNA,a novel mesangium-predominant gene,in the renal tissues of various glomerular diseases" J Am Soc Nephrol. (in press).
[Publications] Toshio Miyata: "Increased oxidative stress in the mouse kidneys with unilateral ureteral obstruction." Kidney International. (in press).
[Publications] Toshio Miyata: "2-Isopropylidenehydrazopo-4-oxo-thiazolidin-5ylacetanilide(OPB-9195)inhibits the neointima proliferation of rat carotid artery following balloon injury:Role of glycoxidation and lipoxidation reactions in vascular tissue damage." FEBS letter. (in press).
[Publications] Toshio Miyata: "2-Isopropylidenehydrazono-4-oxo-thiazolidin-5ylacetanilide(OPB-9195)is a potent inhibitor for glycoxidation and lipoxidation reactions." Biochem Biophys Res Commun. (in press).
[Publications] Toshio Miyata: "Apo E2/E5 mutation in lipoprotein glomerulopathy recurred in transplanted kidney." J Am Soc Nephrol.(in press).
[Publications] Toshio Miyata: "Carbonyl stress in chronic renal failure(Nephrology Forum)." Kidney International. (in press).
[Publications] Toshio Miyata: "Relevance of oxidative stress in long-term complications in hemodialysis." Kidney International. (in press).

1998 Fiscal Year Annual Research Report

腎疾患における高度糖化蛋白の病態生理学的意義に関する共同研究

Principal Investigator

宮田 敏男 東海大学, 総合医学研究所, 講師 (10222332)

Research Products

[Publications] Toshio Miyata: "Funcional quantiative analysis of the genome in cultured human mesangial cells." Kidney International. 53. 154-158 (1998)

[Publications] Toshio Miyata: "Renal catabolism of advanced glycation end products:the fate of pentosidne." Kidney International. 53. 416-422 (1998)

[Publications] Toshio Miyata: "Increased pentosidine,an davanced glycation end products,in plasma and synovial fluid from patients with rheumatoid arthritis and its relation with markers of inflammation." Biochem Biophys Res Commun. 244. 45-49 (1998)

[Publications] Toshio Miyata: "Stress carbonyle et complications a long terme de I uremie" ACTUALITES NEPHROLOGIQUES JEAN HAMBURGER.Ho^^<^>PITAL NECKER 1998. 247-253

[Publications] Toshio Miyata: "Protein-bound acrolein:potential markers for oxidative stress." Proc Natl Acad Sci USA. 95. 4882-4887 (1998)

[Publications] Toshio Miyata: "Alteraitions of synovial tissue and their potential rolu in the deposition of β_2-microglobulin-associated amyloid." Nephrol Dial Transplant. 13. 1465-1475 (1998)

[Publications] Toshio Miyata: "β2-Microgloburin in renal disease." J Am Soc Nephrol. 9. 1723-1735 (1998)

[Publications] Toshio Miyata: "Implication of the glycoxidation and lipoxidation rections in the pathogenesis of dialysis-related amyloidosis." Int J Mol Med. 2. 561-565 (1998)

[Publications] Toshio Miyata: "Plasma level of pentosidine in diabetic patients:an advanced glycation end product." J Am Soc Nephrol. 9. 1681-1688 (1998)

[Publications] Toshio Miyata: "Implication of altered redox regulation by antioxidant enzymes in the increased plasma pentosidine,an advanced glycation end product,in uremia." Biochem Biophys Res Commun. 245. 785-790 (1998)

[Publications] Toshio Miyata: "Autoxidation products of both carbohydrates and lipids are increased in uremic plasma:Is there oxidative stress in uremia?" Kidney International. 54. 1290-1295 (1998)

[Publications] Toshio Miyata: "A mesangium-predominant gene,megsin,is a new serpin up-regulated in lgA nephropathy." J Clin Invest. 102. 828-836 (1998)

[Publications] Toshio Miyata: "Accelerated formation of carboxymethyllysine,an advanced glycation end product,by glyoxal and 3-deoxyglucosone in cultured ratsensoryneurons" Biochem Biophys Res Commun. 248. 93-97 (1998)

[Publications] Toshio Miyata: "Advanced glycation end products co-localization with astoricytes and microglial cells in Alzheimer's disease brain." Acta Neuropathol. 98. 555-558 (1998)

[Publications] Toshio Miyata: "Generation of protein carbonyls by glycation and lipoxidation reactions with autoxidation products of ascorbic acid and polyunsaturated fatty acids." FEBS letter. 437. 24-28 (1998)

[Publications] Toshio Miyata: "Localization of identified advanced glycation end product structure-carboxymethyllysine and pentosidine,in age-related inclusions in humanbrains" Pathology International. 48. 575-579 (1998)

[Publications] Toshio Miyata: "Level of HgCl_2-meditated phosphorylaiton of intracellular proteins determines death of thymic T-lymphocytes with or without DNA fragmentation." J Cellular Biochemistry. 71. 243-253 (1998)

[Publications] Toshio Miyata: "Carbonyl stress in uremia:Accumulation of carbonyls accelerate the formation of pentosidine,an advanced glycation end product." J Am Soc Nephrol. 9. 2349-2356 (1998)

[Publications] Toshio Miyata: "Carbonyl compounds cross-link cellular proteins and activate protein-tyrosine kinase p60_<c-src>" J Cellular Biochemistry. 72. 1-7 (1998)

[Publications] Toshio Miyata: "Alterations in non-enzymatic biochemistry in uremia:Origin and significance of ″carbonyl stress″in long-term uremic complications." Kidney International. 55. 389-399 (1998)

[Publications] Toshio Miyata: "Carbonyl stress:increased carbonyl modification of proteins by autoxidation products of carbohydrates and lipids." Int J Art Org. (in press).

[Publications] Toshio Miyata: "Possible involvement of ″carbonyl stress″ in the pathogenesis of dialysis-related amyloidosis." Am J Med Sci. (in press).

[Publications] Toshio Miyata: "Rapid formation of advanced glycation end products following vascular injury in euglycemic rat carotid artery:Role of oxidative stress." Circulation Research. (in press).

[Publications] Toshio Miyata: "Oxidative stress-induced ″carbonyl stress″ in uremia." Redox Regulation Clinical Application. (in press).

[Publications] Toshio Miyata: "″Carbonyl Stress″ and long-term uremic complications." Advanced in Nephrology. (in press).

[Publications] Toshio Miyata: "Carbonyl stress in long-term uremic complications." Nephrol Dial Transplant. (in press).

[Publications] Toshio Miyata: "″Carbonyl Stress″ and dialysis-related amyloidosis." Dial Transplant. (in press).

[Publications] Toshio Miyata: "Immunohistochemical evidence for an increased oxidative stress and carbonyl modification of proteins by autoxidation products of carbohydrates,lipids,and amino acids in diabetic glomerular lesions." J Am Soc Nephrol. (in press).

[Publications] Toshio Miyata: "Carbonyl stress:Increased carbonyl modification of tissue and cellular proteins in uremia." Peritoneal Dialysis international. (in press).

[Publications] Toshio Miyata: "β2-microglobulin and renal bone disease." Peritoneal Dialysis International. (in press).

[Publications] Toshio Miyata: "A sensitive and specific ELISA for plasma pentosidine." Nephrol Dial Transplant. (in press).

[Publications] Toshio Miyata: "Neurotoxicity of methylglyxal and 3-Deoxyglycose on cultured cortical-neurons:Synergism between glycation and oxidative stress,possibly involved in neurodegnerative diseases." Neurosci letter. (in press).

[Publications] Toshio Miyata: "Development of a polyclonal antibody with broad epitope specificityy for advancedglycation end products and its use for the detection of AGEs in again human Bruch's membrane and choroid." Experimental Eye Research. (in press).

[Publications] Toshio Miyata: "Infuluence of hemodialysis membrane type on pentosidine plasma level,a marker of ″carbonyl stress″." Kidney International. (in press).

[Publications] Toshio Miyata: "Carbonyl stress and diabetic nephropathy." Jpn J Nephrol. (in press).

[Publications] Toshio Miyata: "Implication of carbonyl stress in long-term uremic complications." Blood Purification. (in press).

[Publications] Toshio Miyata: "Advanced glycation end products potentiate human platelet aggregation in vitrα Possible role of oxidative stress." Biochem Biophys Res Commun. (in press).

[Publications] Toshio Miyata: "The first Japan-European Nephrology Forum." Nephrol Dial Transplant. (in press).

[Publications] Toshio Miyata: "Increased carbonyl modification of proteins by lipids and carbohydrates in diabetic nephropathy." Kidney International. (in press).

[Publications] Toshio Miyata: "Increase of the advanced glycation endproduct pentosidine in Bruchs membrane with age." Investigative Ophthalmology Visual Science. (in press).

[Publications] Toshio Miyata: "Expression of megsin mRNA,a novel mesangium-predominant gene,in the renal tissues of various glomerular diseases" J Am Soc Nephrol. (in press).

[Publications] Toshio Miyata: "Increased oxidative stress in the mouse kidneys with unilateral ureteral obstruction." Kidney International. (in press).

[Publications] Toshio Miyata: "2-Isopropylidenehydrazopo-4-oxo-thiazolidin-5ylacetanilide(OPB-9195)inhibits the neointima proliferation of rat carotid artery following balloon injury:Role of glycoxidation and lipoxidation reactions in vascular tissue damage." FEBS letter. (in press).

[Publications] Toshio Miyata: "2-Isopropylidenehydrazono-4-oxo-thiazolidin-5ylacetanilide(OPB-9195)is a potent inhibitor for glycoxidation and lipoxidation reactions." Biochem Biophys Res Commun. (in press).

[Publications] Toshio Miyata: "Apo E2/E5 mutation in lipoprotein glomerulopathy recurred in transplanted kidney." J Am Soc Nephrol.(in press).

[Publications] Toshio Miyata: "Carbonyl stress in chronic renal failure(Nephrology Forum)." Kidney International. (in press).

[Publications] Toshio Miyata: "Relevance of oxidative stress in long-term complications in hemodialysis." Kidney International. (in press).

宮田敏男東海大学, 総合医学研究所, 講師 (10222332)