THE ROLE OF STRESS PROTEINS IN ENDOTOXIN-INDUCED HEPATIC INJURY
THE ROLE OF STRESS PROTEINS IN ENDOTOXIN-INDUCED HEPATIC INJURY
批准号:
09670303
负责人:
YOKOCHI Takashi
金额:
$1.98万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
1997
资助国家:
日本
项目状态:
已结题
起止时间:
1997 至 1998
中文摘要
以d -半乳糖胺(D-GalN)和脂多糖(LPS)作为内毒素休克模型,研究了热休克蛋白(HSPs)作为应激诱导蛋白的表达。在注射D-GalN和LPS的小鼠肝脏中,组成型热休克蛋白70 (HSC70)的表达显著降低,而在单独注射D-GalN或LPS的小鼠肝脏中,HSC70的表达不受影响,其他组成型热休克蛋白60、32和25的表达也在注射D-GalN和LPS的小鼠中降低。另一方面,在注射D-GalN和LPS的小鼠肝脏中检测到诱导型HSP70,而在单独注射D-GalN或LPS的小鼠肝脏中未检测到。同时注射抗肿瘤坏死因子(TNF)- α抗体可防止肝脏中组成型HSC70的表达减少,并导致肝脏中诱导型HSP70的显著表达。当注射D-GalN和重组tnf - α时,也发现组成型HSC70的表达降低。因此,tnf - α被认为在d - galn致敏小鼠对LPS的反应中,对组成型HSC70和诱导型HSP70的表达改变起关键作用。
英文摘要
The expression of heat shock proteins (HSPs) as stress-induced proteins was studied in mice injected with D-galactosamine (D-GalN) and lipopolysaccharide (LPS) as an experimental endotoxic shock model. The expression of constitutive type heat shock protein 70 (HSC70) was significantly reduced in livers of mice injected with D-GalN and LPS, while its expression was unaffected in livers of mice injected with D-GalN or LPS alone, The expression of other constitutive type HSPs, namely HSP 60, 32 and 25 was also reduced in mice injected with D-GalN and LPS.On the other hand, inducible type HSP70 was detected in livers from mice injected with D-GalN and LPS, but not in livers from mice injected with D-GalN or LPS alone.Simultaneous injection of anti-tumor necrosis factor (TNF)-alpha antibody prevented the liver from reduced expression of constitutive type HSC70, and lead to marked expression of inducible type HSP70 in the liver. Reduced expression of constitutive type HSC70 was also found when D-GalN and recombinant TNF-alpha was injected. Therefore, TNF-alpha was suggested to play an critical role on altered expression of constitutive HSC70 and inducible type HSP70 in response of D-GalN-sensitized mice to LPS.
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