1999 Fiscal Year Annual Research Report

分泌型スカベンジャー受容体、ガレクチン3のエンドサイトーシス機能の解析

Research Project

Project/Area Number	11877189
Research Institution	Kumamoto University
Principal Investigator	堀内正公熊本大学, 医学部, 教授 (10117377)
Co-Investigator(Kenkyū-buntansha)	宮崎章熊本大学, 医学部, 講師 (70253721)
Keywords	ガレクチン / マクロファージ / 動脈硬化 / 泡沫細胞 / スカベンジャー受容体
Research Abstract	Chinese hamster ovary cell(CHO細胞)にヒトガレクチン3をトランスフェクションし(CHO-glaectin-3細胞)、種々のリガンドのエンドサイトーシス機能を検討した。まず大腸菌に発現したレコンビナントヒトガレクチン3を抗原としてウサギの抗ヒトガレクチン3ポリクローナル抗体を作成した。この抗体を用いたウェスタンブロット法でCHO-galectin-3細胞におけるヒトガレクチン3の発現を検討すると、CHO由来の内因性ガレクチン3に加え、ヒトガレクチン3が有意に発現していることが確認された。 CHO-galectin-3細胞はメイラード反応後期生成物advanced glycation endproducts(AGE)、アセチル化LDLなどの変性蛋白質を活発に細胞内に取り込んだ。AGEの細胞取り込みは、アセチル化LDLで抑制され、逆にアセチル化LDLの細胞取り込みはAGEにより有意に抑制された。従ってこれらのリガンドは共通の受容体を介して細胞に取り込まれていることが予想される。しかしガレクチン3は細胞貫通部位を持たない分泌蛋白質であることから、それ自身が受容体として機能しているという証拠は得られていない。ガレクチン3は膜蛋白質であるマック2に結合しているといわれており、今後ガレクチン3・マック2複合体が受容体として機能しているかどうかを検討する予定である。また、ガレクチン3発現によりマクロファージスカベンジャー受容体の様な他のスカベンジャー受容体の発現が誘導された可能性があり、この可能性も検討する予定である。

Research Products
(15 results)

All Other

All Publications (15 results)

[Publications] Tajima K et al.: "Herrditary 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 nepgropathy : aminoguanidine ameliorates the overexpression of tumor necrosis factor-alpha and inducible nitric oxide synthase in diabetic rat glomeruil."Diabetologia. 42. 878-886 (1999)
[Publications] Honda K et al.: "Accumualtion of advaced glycation end products in the peritoneal vasculature of continuous ambualtory 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(LDL), accetylatyed LDL and macrophage colony stimulating factor.the activity of oxidized LDL if refractory to the inhibitory cytokine"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 procuct of the Maillard reaction"Diabetes. 48. 1842-1849 (1999)
[Publications] Sakata N et al.: "Increased advanced glycation end products in atheroscleroric lesions of patients with end-stage 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 deproducts are depostited in neuronal hyaline inclusons: 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 inclusons 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 remal AA amyloid"Deposition. Nephrol. Dial. Transplant.. 15. 355-365 (1999)
[Publications] Iwashima Y et al.: "Advanced glycation end product-induced peroxisome prolferator-activated receptor gamma gene expression in the cultred mesangial cells"Biochem. Biophys Res. Commun.. 264. 441-448 (1999)
[Publications] Kaji Y et al.: "Advanced glycation end 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 atherosclertic palques"Atheroscleosis. (in press).

1999 Fiscal Year Annual Research Report

分泌型スカベンジャー受容体、ガレクチン3のエンドサイトーシス機能の解析

Principal Investigator

堀内 正公 熊本大学, 医学部, 教授 (10117377)

Research Products

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

[Publications] Honda K et al.: "Accumualtion of advaced glycation end products in the peritoneal vasculature of continuous ambualtory 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 procuct of the Maillard reaction"Diabetes. 48. 1842-1849 (1999)

[Publications] Sakata N et al.: "Increased advanced glycation end products in atheroscleroric lesions of patients with end-stage 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 deproducts are depostited in neuronal hyaline inclusons: 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 inclusons 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 remal AA amyloid"Deposition. Nephrol. Dial. Transplant.. 15. 355-365 (1999)

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

[Publications] Kaji Y et al.: "Advanced glycation end 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 atherosclertic palques"Atheroscleosis. (in press).

堀内正公熊本大学, 医学部, 教授 (10117377)