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Effect of glucose and cytokines on apoptosis of vascular smooth muscle cells

Research Project

Project/Area Number 09671083
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内分泌・代謝学
Research InstitutionAichi Medical University

Principal Investigator

SAKAKIBARA Fumihiko  Aichi Medical University, First Department of Internal Medicine, Instructor, 医学部, 講師 (60273231)

Co-Investigator(Kenkyū-buntansha) YAMANOUCHI Kunio  Aichi Medical University, First Department of Internal Medicine, Associate Professor, 医学部, 助教授 (60135366)
KUSUNOKI Masataka  Aichi Medical University, First Department of Internal Medicine, Instructor, 医学部, 講師 (80214956)
近田 研  愛知医科大学, 医学部, 講師 (60155299)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1999: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1998: ¥300,000 (Direct Cost: ¥300,000)
Keywordsapoptosis / atherosclerosis / glucose / INF -γ / IL-1β / TNF-α / cytokine / diabetes / 平滑筋細胞 / 増殖 / アポトーシス / ブドウ糖 / インスリン / サイトカイン
Research Abstract

We investigated whether glucose and cytokines can trigger apoptosis of VSMC of rabbit aorta. VSMC were cultured for <72 hours in DMEM containing 5.5 or 55 mM glucose with INF -γ(400 U/mL), IL-1β (100 U/mL), and TNF-α (400 U/mL), each or together. DNA fragments, as an evidence of apoptosis, were detected in situ by using TUNEL method. Quantification of nuclear labeling was performed by counting the percentage of TUNEL-positive cells. No significant difference between 5.5 and 55 mM glucose of percentage of apoptotic cell was observed. With 5.5 mM glucose in the presence of INF -γ, IL-1β and TNF-α each alone percentage of apoptotic cell did not increased significantly (<4%). However, 29.4±6.9% of VSMC in the cultures cotreated with 3 cytokines for 72 hours showed positive staining with TUNEL(p<0.05 versus untreated with cytokines). With 55 mM glucose the same tendency of results was harvested. Increase VSMC proliferation under hyperglycemia has already been reported. Although these cytokines indeces apoptosis, hyperglycemia does not increase the induction of apoptosis cooperatively with cytokines. Since hyperglycema does not promote the apoptosis but proliferation of VSMC, diabetes may often cause progression of atherosclerosis.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] 榊原文彦ら: "高濃度グルコースは,血管壁平滑筋細胞にアポトーシスを誘導しない"糖尿病. 42. S-170 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 榊原文彦ら: "高濃度グルコースは,血管壁平滑筋細胞のサイトカインによるアポトーシスの誘導に影響を与えない"糖尿病. 43. S-210 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sakakibara F et al.: "Glucose does not affect apoptosis of rascular smooth muscle cells induced by invitro stimulation with cytokines"Diabetes res clin pr. 50. Suppl-S-36 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sakakibara F, Kusunoki M, Yamanouchi K, Kato K, Okabayashi N, Usui K, Iriyama A, Kakumu S.: "Glucose does not affect apoptosis of vascular smooth muscle cells induced by in vitro stimulation with cytokines."Diabetes res clin pr. 50 Supplement. S-367 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kusunoki M, Hara T, Tsutsumi K, Nakamura T, Miyata T, Sakakibara F, Sakamoto S, Ogawa H, Nakaya Y, Storlien LH.: "The lipoprotein lipase activator, NO-1886, suppresses fat accumulation and insulin resistance in rats fed a high-fat diet."Diabetologia. 43. 875-80 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakamura J, Kato K, Hamada Y, Nakayama M, Chaya S, Nakashima E, Naruse K, Kasuya Y, Mizubayashi R, Miwa K, Yasuda Y, Kamiya H, Ienaga K, Sakakibara F, Koh N, Hotta N.: "A protein kinase C-beta-selective inhibitor ameliorates neural dysfunction in streptozotocin-induced diabetic rats."Diabetes. 48. 2090-5 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sasaki H, Nakamura J, Koh N, Hamada Y, Hara T, Chaya S, Nakashima E, Naruse K, Kato K, Kasuya Y, Sakakibara F, Hotta N.: "Effect of vitamin E and allylamine on the proliferation of cultured aortic smooth muscle cells from streptozotocin-induced diabetic rats."Life Sci. 64. 2317-25 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Suzuki K, Kawamura T, Sakakibara F, Sasaki H, Sano T, Sakamoto N, Hotta N.: "Effect of aldose reductase inhibitors on glucose-induced changes in sorbitol and myoinositol metabolism in human neutrophils."Diabet Med. 16. 67-73 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakamura J, Koh N, Sakakibara F, Hamada Y, Hara T, Sasaki H, Chaya S, Komori T, Nakashima E, Naruse K, Kato K, Takeuchi N, Kasuya Y, Hotta N.: "Polyol pathway hyperactivity is closely related to carnitine deficiency in the pathogenesis of diabetic neuropathy of streptozotocin-diabetic rats."J Pharmacol Exp Ther. 287. 897-902 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hamada Y, Nishimura C, Koh N, Sakakibara F, Nakamura J, Tanimoto T, Hotta N.: "Influence of interindividual variability of aldose reductase protein content on polyol-pathway metabolites and redox state in erythrocytes in diabetic patients."Diabetes Care. 21. 1014-8 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hotta N, Nakamura J, Sakakibara F, Hamada Y, Hara T, Mori K, Nakashima E, Sasaki H, Kasama N, Inukai S, Koh N.: "Electroretinogram in sucrose-fed diabetic rats treated with an aldose reductase inhibitor or an anticoagulant."Am J Physiol. 273. E965-71 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hotta N, Koh N, Sakakibara F, Nakamura J, Hara T, Hamada Y, Fukasawa H, Kakuta H, Sakamoto N.: "Effect of an aldose reductase inhibitor on abnormalities of electroretinogram and vascular factors in diabetic rats."Eur J Pharmacol. 326. 45-51 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Mori K, Nakamura J, Koh N, Sakakibara F, Hamada Y, Hara T, Komori T, Nakashima E, Naruse K, Takeuchi N, Hotta N.: "Increased alanine uptake and lipid synthesis from alanine in isolated hepatocytes of Wistar-Kyoto fatty rats : an inhibitory effect of biguanides."Can J Physiol Pharmacol. 75. 179-84 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakamura J, Koh N, Sakakibara F, Hamada Y, Wakao T, Sasaki H, Mori K, Nakashima E, Naruse K, Hotta N.: "Diabetic neuropathy in sucrose-fed Otsuka Long-Evans Tokushima fatty rats : effect of an aldose reductase inhibitor, TAT."Life Sci. 60. 1847-57 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 榊原文彦ら: "高濃度グルコースは血管平滑筋細胞にアポトーシスを誘導しない"糖尿病. 41Supple. S170 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 榊原文彦ら: "高濃度グルコースは血管壁平滑筋細胞のサイトカインによるアポトーシスの誘導に影響を与えない"糖尿病. 42Supple(in press). (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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