Function of protein kinase C (PKC) in the regulation of apoptosis related hyperglycemia in vascular smooth muscle cells.

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 12671105
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Gifu University
• Principal Investigator: YAMAMOTO Mayumi School of Medicine Assistant Prof., 医学部, 助手 (40313879)
• Project Period (FY): 2000 – 2002
• Keywords: atherosclerosis / diabetes / PKC / apoptosis / apoptosis related protein / cell cycle / Western blot / flowcytometry

Research Abstract

Atherosclerosis is accelerated by the coexistence of diabetes mellitus. Hyperglycemia is an important etiologic factor in the development of vascular complications.
(1) Effect of high glucose on cell proliferation and apoptosis in vascular smooth muscle cells (VSMC).
High glucose stimulated cell proliferation and suppressed induction of apoptosis significantly in VSMC.
(2) Effect of overexpression of PKC isozyme on cell proliferation and apoptosis in VSMC.
Overexpression of PKC-βI stimulated cell proliferation and inhibited apoptosis expression in VSMC.
In contrast, Overexpression of PKC-βII inhibited cell proliferation and increased induction of apoptosis in VSMC.
(3) Effect of high glucose on the expression of PKC isozymes and apoptosis-related proteins, Bcl-xL and Bfl-1/A1.
Treatment with a high glucose caused a significant decrease in apoptosis in CASMC compared with the same cells treated with a physiologically normal glucose concentration. Treatment of CASMC with high glucose concentration markedly increased mRNA expressions of bcl-xL and bfl-1/A1 compared with cells treated with normal glucose. High glucose suppressed apoptosis via upregulation of bcl-xL and bfl-1/A1 levels. High glucose-induced increase in the expression of antiapoptotic proteins may be important in the development of atherosclerosis in diabetic patients.

Research Products

• [Publications] Sakuma H., Yamamoto M, et al.: "High glucose inhibits apoptosis in human coronary artery Smooth muscle cells by increasing bcl-xL and bfl-1/Al"Am. J. Physiol. Cell Physiol.. 283. c244-c428 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Patel N.A., Yamamoto M, et al.: "Phosphoinosiode 3-kinase medicates PKC-βII mRNA destabilization in vascular smooth muscle cells exposed to high glucose"Arch Biochem Biophys. 403. 111-120 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Patel N.A., Eichler DC, et al.: "The protein kinase C βII exon confers mRNA instability in the presence of high glucose concentrations"J. Biol. Chem. 278. 1149-1157 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Okumura M., Yamamoto M, et al.: "Leptin and high glucose simulate cell proliferation in MCF-7 human breast cancer cells : reciprocal involvement of PKC-α and PPAR expression"Biochim Biophys Acta. 1592. 107-116 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Sakuma H., Yamamoto M, et al.: "High glucose-induced Suppression of apoptosis mediated by alteration of Bcl-z family expressions in human coronary artery smooth muscle cells"Acta Sch Med GIFU. 50. 1-9 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Hiroyuki Yamaguchi, Herman Friedman et al.: "Chlamydia pneumoniae resists antibiotics in lymphocytes"Antimicrob Agents Chemother. (in press). (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Sakuma H, Yamamoto M., Okumura M., Kojima T., Maruyama T., Yasuda K.: "High glucose inhibits apoptosis in human coronary artery smooth muscle cells by increasing bcl-xL and bfl-1/A1"AmJ Physiol Cell Physiol. 283. C422-C428 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Sakuma H., Yamamoto M., Okumura M., Kojima T., Maruyama T., Yasuda K.: "High glucose-induced suppression of apoptosis mediated by alteration of Bcl-2 family expressions in human coronary artery smooth muscle cells."Acta Sch Med Univ Gifu. 50. 1-9 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Okumura M., Yamamoto M., Sakuma H., Kojima T., Maruyama T., Jamali M., Cooper D.R., Yasuda K.: "Leptin and high glucose stimulate cell proliferation in MCF-7 human breast cancer cells : reciprocal involvement of PKC-α and PPAR expression"Biochim Biophys Acta. 1592. 107-116 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Patel N.A., Yamamoto M., Illingworth P., Mancu D., Mebert K., Chappell D.S., Watson J.E., Cooper D.R.: "Phosphoinositide 3-kinase mediates PKC-βII mRNA destabilization in vascular smooth muscle cells exposed to high glucose"Arch Biochem Biophys. 403. 111-120 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Patel N.A., Eichler D.C., Chappell D.S., Illingworth P., Chalfant C.E., Yamamoto M., Dean N.M., Wyatt J.R., Mebert K., Watson J.E., Cooper D.R.: "The proltein knase C βII exon confers mRNA instability in the presence of high glucose concentrations"J Biol Chem. 278. 1149-1157 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Hiroyuki Yamaguchi, Herman Friedman, Mayumi Yamamoto, Keigo Yasuda, Yoshimasa Yamamoto: "Chlamydia pneumoniae resists antibiotics in lymphocytes"Antimicrob Agents Chemother. (in press). (2003)
  • Description: 「研究成果報告書概要(欧文)」より