Overproduction of Nε-(Carboxymethyl)lysine-Induced Neovascularization in Cultured Choroidal Explant of Streptozotocin-Diabetic Rat

• Kobayashi Shinjiro

  Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokuriku University

• Suzuki Miho

  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

• Horiuchi Seikoh

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

• Hagino Nobuyoshi

  Tulane University Health Sciences Center, Tulane University Hebert Center, Bldg. 30, US–Japan Biomedical Research Laboratories

書誌事項

タイトル別名

• Overproduction of N.EPSILON.-(Carboxymethyl)lysine-Induced Neovascularization in Cultured Choroidal Explant of Streptozotocin-Diabetic Rat
• Overproduction of N イプシロン Carboxymethyl lysine Induced Neovascularization in Cultured Choroidal Explant of Streptozotocin Diabetic Rat

抄録

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.

収録刊行物

• Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ

  Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ 27 (10), 1565-1571, 2004

  公益社団法人 日本薬学会

キーワード

• choriocapillaris
• neovascularization
• <i>N</i>^ε-(carboxymethyl)lysine (CML)
• advanced glycation end product
• diabetic retinopathy
• streptozotocin

詳細情報

• CRID: 1390001204624710016
• NII論文ID: 110003608655
• NII書誌ID: AA10885497
• DOI: 10.1248/bpb.27.1565
• ISSN: 13475215
• ISSN: 09186158
• NDL書誌ID: 7097282
• PubMed: 15467196
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I7097282
• Web Site: http://www.jstage.jst.go.jp/article/bpb/27/10/27_10_1565/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2006205031
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可