Dataset Information

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

ABSTRACT: 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, NG-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.

SUBMITTER: Hirvonen MR

PROVIDER: S-EPMC1217283 | biostudies-other | 1996 May

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:Heat stress (HS) adversely affects several physiological responses in organisms, but the underlying molecular mechanisms involved are yet to be fully understood. L-Citrulline (L-Cit) is a nutraceutical amino acid that is gaining research interest for its role in body temperature regulation and nitric oxide synthesis. This study investigated whether dietary supplementation with L-Cit (1% of basal diet) could ameliorate the effects of acute HS on thermotolerance, redox balance, and inflammatory responses of broilers. Ross 308 broilers (288 chicks) were subjected to two environments; thermoneutral at 24°C (TNZ) or HS at 35°C for 5 h, and fed two diets; control or L-Cit. The results showed that HS increased the ear, rectal (RT), and core body (CBT) temperatures of broilers, along with higher respiratory rate. The RT and CBT readings were intermittently affected with time effect, whereas, L-Cit supplementation lowered the mean CBT than the control diet. Antioxidant assays showed that superoxide dismutase was increased during HS, while, catalase was promoted by L-Cit supplementation. In addition, L-Cit induced glutathione peroxidase activity compared to the control diet during HS. Hypothalamic heat shock protein (HSP)-90 was upregulated by HS, but L-Cit downregulated heat shock factor (HSF)-1, and HSP 60 mRNA expressions. HSF 3 mRNA expression was downregulated by L-Cit under TNZ condition. More so, HS increased the plasma nitric oxide (NO) concentration but lowered the total NO synthase (tNOS) activity. In contrast, L-Cit supplementation limited NO production but increased the tNOS activity. Arginase activity was increased in the control fed group during HS but L-Cit supplementation lowered this effect. The NOS-COX pathway was significantly affected under TNZ condition, since L-Cit supplementation downregulated the mRNA expression of iNOS-COX2 in the hypothalamus, and further reduced the serum PGE2 concentration. Together, these data indicates that L-Cit influenced the antioxidant defense, heat shock response and nitric oxide regeneration both under thermoneutral and HS conditions; and that L-Cit may be directly and/or indirectly involved in the central regulation of body temperature.

Dataset Information

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets