1999 Fiscal Year Annual Research Report

メイラード反応後期生成物(AGE)の構造と生物医学的意義に関する研究

Research Project

Project/Area Number	10044305
Research Category	Grant-in-Aid for Scientific Research (A)
Research Institution	Kumamoto University
Principal Investigator	堀内正公熊本大学, 医学部, 教授 (10117377)
Co-Investigator(Kenkyū-buntansha)	永井竜児熊本大学, 医学部, 助手 (20315295) 宮崎章熊本大学, 医学部, 講師 (70253721)
Keywords	糖尿病合併症 / メイラード反応 / AGE / AGE受容体 / 老化
Research Abstract	1.AGEの主要構造体の解析メチルグリオキサール由来AGE構造体の同定 : 既にBaynes博士との共同研究によってメチルグリオキサール由来のAGE構造体としてNε-(carboxyethyl)lysine(CEL)が同定されている。本年度新たに調製したCELに対するモノクローナル抗体を用いた解析から、CELがメイラード反応に伴って生成すること、さらにCELはヒトの気管支、胃、肝臓、胸腺などの内皮細胞、又、動脈内皮細胞、マクロファージ等に蓄積していることが明らかとなった。 2.AGEの生体内局在・動態の解析血中AGEの免疫学的測定 : 既にMonnier博士との共同研究によって血液中にAGE、特にNε-(carboxymethl)lysine(CML)に対する自己抗体が存在し、血中AGEの免疫学的測定を困難にしている可能性が示された。本年度、血液試料をプロテアーゼ処理することによって自己抗体を分解し、血中pentosidine含量をモノクローナル抗pentosidine抗体で測定する系を確立した。 3.AGE受容体の構造と機能解明 AGE受容体ファミリーとして報告されているGalectin-3をCHO細胞に過剰発現させると(CHO-Gal-3)、AGE蛋白のみならず、酸化LDLをもリガンドとして認識するすることが明らかとなっている。これに対して、Baynes博士と共同で開発したGalectin-3ノックアウトマウスの腹腔マクロファージでは、AGE蛋白の取り込みは野生型に比べて増加することが明らかとなった。さらに、Smedsrod博士との共同研究によって、酸化LDL受容体として報告されているCD36を過剰発現させたCHO細胞を作製した結果、本細胞は野生型に比べてAGE蛋白の取り込みが増加し、CD36がAGE受容体として機能している可能性が示された。

Research Products
(15 results)

All Other

All Publications (15 results)

[Publications] Sakata N et al.: "Increased advanced glycation end products in atheroscleroric lesions of patients with endstage renal disease"Atherosclerosis. 142. 67-77 (1999)
[Publications] Abiko,T et al.: "Relationship between autofluorescence and advanced glycation end products in diabetic lenses."Exp. Eye Res.. 68. 361-366 (1999)
[Publications] Shibata N et al.: "Advanced glycation endproducts are deposited in neuronal hyaline inclusions: a study on familial amyotrophic lateral sclerosis with superoxide dismutase-1 mutation"Acta Neuropathol.. 97. 240-246 (1999)
[Publications] Kato S et al.: "Astrocytic hyaline inclusions contain advanced glycation endproducts in familial amyotrophiclateral sclerosis with superoxide dismutase 1 gene mutation: imunohisto-chemical and immunoelectron microscopical analyses."Acta Neuropathol.. 97. 260-266 (1999)
[Publications] Ando K et al.: "Membrane proteins of human erythrocytes are modified by advanced glycation end products (AGEs) during aging in the circulation."Biochem. Biophys. Res. Commun.. 258. 123-127 (1999)
[Publications] Uesugi N et al.: "Glycoxidative modification promotes renal AA amyloid"Deposition. Nephrol. Dial. Transplant.. 15. 355-365 (1999)
[Publications] Tajima K et al.: "Hereditary ceruloplasminemia deficiency increases advanced glycation end products in the brain"Neurology. 53. 619-622 (1999)
[Publications] Sugimoto H et al.: "Advanced glycation end products-cytokine-nitric oxide sequence pathway in the development of diabetic nephropathy: aminoguanidine ameliorates the overexpression of tumor necrosis factor-alpha and inducible nitric oxide synthase in diabetic rat glomeruli"Diabetologia. 42. 878-886 (1999)
[Publications] Honda K et al.: "Accumualtion of advanced glycation end products in the peritoneal vasculature of continuous ambulatory peritoneal dialysis patients with low ultra-filtration"Nephrol. Dial. Transplant. 14. 1541-1549 (1999)
[Publications] Sasaki T et al.: "The effect of interleukin (IL)-4 and IL-10 on macrophage growth-stimulating activities of oxidized low density lipoprotein (IDL), accetylated IDL and macrophage colony stimulating factor: the actrivity of oxidized IDL is refractory to the inhibitory cytokines"Pharm. Bull.. 22. 1002-1006 (1999)
[Publications] Sasaki T et al.: "Induction of GM-CSF production of macrophages by advanced glycation end products of the Maillard reaction"Biosci. Biotechnol. Biochem.. 63. 2011-2013 (1999)
[Publications] Shibayama R et al.: "Autoantibody Against Nε-(carboxymehtyl)lysine: an advanced glycation end product of the Maillard reaction"Diabetes. 48. 1842-1849 (1999)
[Publications] Iwashima Y et al.: "Advanced glycation end product-induced peroxisome proliferator-activated receptor gamma gene expression in the cultured mesangial cells"Biochem. Biophys Res. Commun.. 264. 441-448 (1999)
[Publications] Kaji Y et al.: "Advanced glycation en products in diabetic corneas"Invest. Ophthalmol. Vis. Sci.. 41. 362-368 (1999)
[Publications] Imanaga Y et al.: "In vivo and in vitro evidences for glycoxidation of low density lipoprotein in human atherosclerotic plaques"Atherosclerosis. (in press).

1999 Fiscal Year Annual Research Report

メイラード反応後期生成物(AGE)の構造と生物医学的意義に関する研究

Principal Investigator

堀内 正公 熊本大学, 医学部, 教授 (10117377)

Research Products

[Publications] Sakata N et al.: "Increased advanced glycation end products in atheroscleroric lesions of patients with endstage renal disease"Atherosclerosis. 142. 67-77 (1999)

[Publications] Abiko,T et al.: "Relationship between autofluorescence and advanced glycation end products in diabetic lenses."Exp. Eye Res.. 68. 361-366 (1999)

[Publications] Shibata N et al.: "Advanced glycation endproducts are deposited in neuronal hyaline inclusions: a study on familial amyotrophic lateral sclerosis with superoxide dismutase-1 mutation"Acta Neuropathol.. 97. 240-246 (1999)

[Publications] Kato S et al.: "Astrocytic hyaline inclusions contain advanced glycation endproducts in familial amyotrophiclateral sclerosis with superoxide dismutase 1 gene mutation: imunohisto-chemical and immunoelectron microscopical analyses."Acta Neuropathol.. 97. 260-266 (1999)

[Publications] Ando K et al.: "Membrane proteins of human erythrocytes are modified by advanced glycation end products (AGEs) during aging in the circulation."Biochem. Biophys. Res. Commun.. 258. 123-127 (1999)

[Publications] Uesugi N et al.: "Glycoxidative modification promotes renal AA amyloid"Deposition. Nephrol. Dial. Transplant.. 15. 355-365 (1999)

[Publications] Tajima K et al.: "Hereditary ceruloplasminemia deficiency increases advanced glycation end products in the brain"Neurology. 53. 619-622 (1999)

[Publications] Honda K et al.: "Accumualtion of advanced glycation end products in the peritoneal vasculature of continuous ambulatory peritoneal dialysis patients with low ultra-filtration"Nephrol. Dial. Transplant. 14. 1541-1549 (1999)

[Publications] Sasaki T et al.: "Induction of GM-CSF production of macrophages by advanced glycation end products of the Maillard reaction"Biosci. Biotechnol. Biochem.. 63. 2011-2013 (1999)

[Publications] Shibayama R et al.: "Autoantibody Against Nε-(carboxymehtyl)lysine: an advanced glycation end product of the Maillard reaction"Diabetes. 48. 1842-1849 (1999)

[Publications] Iwashima Y et al.: "Advanced glycation end product-induced peroxisome proliferator-activated receptor gamma gene expression in the cultured mesangial cells"Biochem. Biophys Res. Commun.. 264. 441-448 (1999)

[Publications] Kaji Y et al.: "Advanced glycation en products in diabetic corneas"Invest. Ophthalmol. Vis. Sci.. 41. 362-368 (1999)

[Publications] Imanaga Y et al.: "In vivo and in vitro evidences for glycoxidation of low density lipoprotein in human atherosclerotic plaques"Atherosclerosis. (in press).

堀内正公熊本大学, 医学部, 教授 (10117377)