2003 Fiscal Year Final Research Report Summary
The regulatory effects of ubiquitin-proteasome pathways on Fas-mediated apotosis
| Project/Area Number |
13670740
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
HANO Takuzo Wakayama Medical University, Cardiovascular medicine, Associate Professor, 医学部, 助教授 (90156381)
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| Co-Investigator(Kenkyū-buntansha) |
IMANISHI Toshio Wakayama Medical University, Cardiovascular Medicine, Assitant Professor, 医学部, 講師 (00285389)
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| Project Period (FY) |
2001 – 2003
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| Keywords | Apoptosis / Fas-Fas ligand signal / Proteasome / Oxidized LDL / Endothelium / Vascular smooth muscle cells |
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| Research Abstract |
We examined the effect of ubiquitin-proteasome pathway on both the expression of either Fas or Fas-related mRNA and sensitization of Fas-mediated apoptosis. Furthermore, we examined the clinical significance of Fas-mediated apoptosis, especially focused on acute coronary syndrome. The results are as follows. Experimental study: 1)The ubiquitin-proteasome pathway are involved in the susceptibility of Fas-mediated apoptosis in both cultured human vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). That is, the up-regulation of surface Fas induced by the inhibition of proteasome activity leads to the sensitization of Fas-mediated apoptosis. Clinical study: 1)The patients with acute coronary syndrome had higher concentrations in both soluble FasL in peripheral blood and membrane FasL on monocytes than those of either healthy volunteers or the patients with stable angina. 2)There had no correlations of the concentrations between soluble FasL and membrane FasL, which suggests that both are regulated by different mechanisms. In conclusions. 1)Fas-niediated apoptosis in both VSMCs and ECs, at least in vitro, is regulated by ubiquitin-proteasome pathway. 2)Fas-FasL signal transduction may be related to the pathphysiolgy of acute coronary syndrome.
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