Overproduction of N^ε-(Carboxymethyl)lysine-Induced Neovascularization in Cultured Choroidal Explant of Streptozotocin-Diabetic Rat(Pharmacology)

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概要

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• Action of N^ε- (carboxymethyl) lysine (CML) adduct, an advanced glycation end product, was investigated on neovascularization of cultured choroidal explants in streptozotocin (STZ) -diabetic rat. The choroidal explants of early (4 weeks after an injection of 60 mg/kg STZ) and advanced (8 months after the STZ injection) diabetic rats, and age-matched normal rats were cultured in fibrin gel with Dulbecco's modified Eagle medium containing fetal bovine serum. The number of budded microvessel-like structures was counted and used as an index of in vitro neovascularization. Choroidal explants in the early diabetic stage released vascular endothelial growth factor (VEGF) and tended to increase tumor necrosis factor (TNF) α and platelet-derived growth factor (PDGF)-B, and concomitantly facilitated growth of sprout and buds, compared to the normal control. When choroidal explants were stimulated with CML-human serum albumin (HSA), its releasing effect was in the order VEGF>TNFα>PDGF-B. CML-HSA and CML-bovine serum albumin augmented the neovascularization in the cultured diabetic explant and their actions did not virtually differ. A monoclonal anti-CML antibody (6D12) inhibited the neovascularization in the advanced diabetes greater than that in the early diabetes. Inhibitory actions of anti-VEGF and anti-TNFα antibodies on the neovascularization were similar to that of the anti-CML antibody in the diabetes. In conclusion, CML adducts were accumulated and over-produced the actions of VEGF, TNFα and PDGF-B in the choroidal explant during diabetes in an age-dependent manner. TNFα and VEGF are likely to play a predominant role for the CML-induced choroidal neovascularization.

• 社団法人日本薬学会の論文
• 2004-10-01

著者

• SUZUKI Miho

  Department of Biotechnology, The University of Tokyo

• Horiuchi Seikoh

  Department of Biochemistry, Kumamoto University School of Medicine

• Horiuchi Seikoh

  熊本大学 医学薬学研究部病態生化学

• Horiuchi S

  Department Of Biochemistry Kumamoto University School Of Medicine

• Horiuchi Seikoh

  帝京大学 薬

• Horiuchi Seikoh

  Department Of Medical Biochemistry Kumamoto University Graduate School Of Medical Sciences

• KOBAYASHI Shinjiro

  Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokuriku University

• TSUNEKI Hiroshi

  Department of Clinical Pharmacology, Toyama Medical and Pharmaceutical University

• NAGAI Ryoji

  Department of Medical Biochemistry, Kumamoto University Graduate School of Medical Sciences

• HAGINO Nobuyoshi

  Tulane University Health Sciences Center, Tulane University Hebert Center, Blds. 30, US-Japan Biomed

• Suzuki Miho

  Department Of Biotechnology The University Of Tokyo

• Horiuchi Seikoh

  Department Of Biochemistry Kumamoto University

• Kobayashi Shinjiro

  Department Of Chemical Pharmacology Toyama Medical And Pharmaceutical University

• Suzuki Miho

  Department Of Pharmacology Faculty Of Pharmaceutical Sciences Hokuriku University

• Tsuneki H

  Department Of Clinical Pharmacology University Of Toyama

• Kobayashi S

  Kyoritsu Coll. Pharmacy

• Horiuchi Seikoh

  Biochemistry Kumamoto University School Of Medicine

• Nagai Ryoji

  Department Of Biochemistry Kumamoto University

• Suzuki Masahiko

  Department Of Pharmacology Faculty Of Pharmaceutical Sciences Hokuriku University

• Tsuneki Hiroshi

  Department Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences Toyama Medical And Pharmaceut

• Tsuneki Hiroshi

  富山医科薬科大学大学院薬学研究科 臨床薬理学講座

• Hagino Nobuyoshi

  Tulane University Health Sciences Center Tulane University Hebert Center

• Kobayashi Shinjiro

  Department Of Clinical Pharmacology Faculty Of Pharmaceutical Sciences Hokuriku University:organizat

• Suzuki Miho

  Department Of Biology Faculty Of Science Nagoya University

• TSUNEKI Hiroshi

  Department of Clinical Pharmacology,Graduate School of Pharmaceutical Sciences,Toyama Medical and Pharmaceutical

• Kobayashi Shinjiro

  Department of Applied Chemistry, Faculty of Engineering, Kyushu University

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