Heat shock proteins and macrophage resistance to the toxic effects of nitric oxide

被引:65
作者
Hirvonen, MR
Brune, B
Lapetina, EG
机构
[1] UNIV ERLANGEN NURNBERG, FAC MED, D-91054 ERLANGEN, GERMANY
[2] GLAXO WELLCOME INC, DIV CELL BIOL, RES TRIANGLE PK, NC 27709 USA
[3] NATL PUBL HLTH INST, DEPT TOXICOL, SF-70211 KUOPIO, FINLAND
关键词
D O I
10.1042/bj3150845
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Nitric oxide (NO) functions as a pathophysiological mediator in mammalian tissues. Activated macrophages produce NO as a non-specific immune response directed against invading bacteria or micro-organisms. The same macrophages that initiate the production of NO also can be toxically affected by NO. Incubation of RAW 264.7 macrophages with lipopolysaccharide (LPS) and/or interferon-gamma (INF-gamma) induced the formation of NO by the activation of a cytokine-inducible NO synthase (NOS). The viability of these macrophages was inversely correlated with the formation of nitrite, a final NO-oxidation product measurable in the incubation medium. The addition of an NOS inhibitor, N-G-monomethyl-L-arginine, diminished NO formation and preserved cell viability in a dose- and time-dependent fashion. Treatment of macrophages with ten cycles of non-lethal doses of LPS and INF-gamma, each followed by subculturing of the surviving cells, resulted in cell resistance to the NO toxic insult induced by LPS and INF-gamma. These resistant macrophages showed a 2-fold increase in the expression of the constitutive heat shock protein (HSC 70) which is known to be involved in protecting cells against the action of various metabolic insults. Our results establish a link between cell resistance to the toxic effects of NO, and the expression of heat shock proteins in RAW 264.7 macrophages.
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收藏
页码:845 / 849
页数:5
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