Continuous exposure to high concentrations of nitric oxide leads to persistent inhibition of oxygen consumption by J774 cells as well as extraction of oxygen by the extracellular medium

Orsi, A; Beltrán, Belén; CLEMENTI, Emilio; Hallén, Katarina; Feelisch, Martin; MONCADA, Salvador

doi:10.1042/0264-6021:3460407

Cited by 25 publications

(17 citation statements)

References 19 publications

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“…To achieve this, each value was calculated as the percentage of the inhibition of oxygen consumption that was achieved by addition at that time point of 500 nM myxothiazol, the inhibitor of complex III. Initially Ͼ95% of oxygen consumption was found to be mitochondrial (and therefore inhibited by myxothiazol), but after Ϸ2 h some of the oxygen consumption was found to be due to an additional chemical, non-mitochondrial mechanism similar to the one we have described previously in cells treated with exogenous NO (9).…”

Section: Methodsmentioning

confidence: 82%

Inhibition of mitochondrial respiration by endogenous nitric oxide: A critical step in Fas signaling

Beltrán

Quintero

García-Zaragozá

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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124

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We have found that activation of human adult T cell leukemia (Jurkat) cells with anti-Fas Ab leads, in a concentration-dependent manner, to an early burst of production of nitric oxide (NO), which inhibits cell respiration. This results in mitochondrial hyperpolarization, dependent on the hydrolysis of glycolytic ATP by the F1Fo-ATPase acting in reverse mode. During this early phase of activation, there is a transient release of superoxide anion. All these processes can be prevented by an inhibitor of NO synthase. Approximately 2 h after stimulation with anti-Fas Ab, a distinct second phase can be detected. This comprises a concentrationdependent collapse in mitochondrial membrane potential, a second wave of free radical production, and activation of caspase-8 leading to apoptosis. This second phase is abolished by an inhibitor of caspase activation. In contrast, inhibition of NO synthesis leads to an enhancement and acceleration of these latter processes, suggesting that the early NO-dependent phase represents a protective mechanism. The significance of the two phases in relation to cell survival and death remains to be studied.

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Section: Methodsmentioning

confidence: 82%

Inhibition of mitochondrial respiration by endogenous nitric oxide: A critical step in Fas signaling

Beltrán

Quintero

García-Zaragozá

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

124

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“…The exposure of cells to NO results in a persistent decrease of respiration due to selective redox-dependent inhibition of mitochondrial complex I. This inhibition, which occurred without detectable production of ONOO -, was preceded by a decrease in the concentration of GSH and is likely to be due to nitrosation of thiols relevant for the functioning of mitochondrial complex I [29].…”

Section: Discussionmentioning

confidence: 99%

Renal Antioxidant Status in Rats with Hypertension Induced by N Sup Omega Nitro-<i>L</i>-Arginine Methyl Ester

Fadıllıoğlu

Erdoğan

Polat

et al. 2002

Kidney Blood Press Res

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Nitric oxide (NO) has a role in the etiopathogenesis of hypertension. Relaxation of vascular smooth muscles is failed when NO production is reduced leading to increased vascular peripheral resistance. N sup omega nitro-L-arginine methyl ester (L-NAME) is one of the inhibitors of NO production. The aim of this study was to investigate oxidant-antioxidant systems of renal tissue in rats with hypertension induced by L-NAME. Rats were divided into three groups: control group and study groups treated with 100 or 500 mg/l L-NAME in drinking water for 15 days. The activities of catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), and the levels of malondialdehyde (MDA) and NO were studied in the renal tissue after hypertension induction. Arterial blood pressure was increased in both L- NAME groups. CAT activity of 500-mg L-NAME group was higher than control. GSH-Px activity of 500-mg L-NAME group was decreased compared with 100-mg ones. NO level was lower in 500-mg L-NAME group than control. MDA levels in both L-NAME groups were decreased compared with control. In conclusion, hypertension was induced with oral L-NAME treatment. Increased CAT activity was compensated with decreased GSH-Px activity in 500-mg L-NAME group. Both study groups were protected from lipid peroxidation with NO inhibition.

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“…Incubation of cells with NO donors is reported to result in a rapid and reversible inhibition of cytochrome-c oxidase (complex IV), which can be reversed by removing NO (4,8,13). After prolonged incubation, cells show an additional inhibition of respiration, which appears to be due to inhibition of complex I (4,8,35,36) and could be prevented or reversed by thiols (such as GSH-ethyl ester) or exposure to "cold" light (illumination from a halogen bulb) (4,8).…”

Section: Snap Prevents Hif-1␣ Protein Accumulation In Hep 3b and Pc-1mentioning

confidence: 99%

Role of nitric oxide in the regulation of HIF-1α expression during hypoxia

Agani

Puchowicz

Chávez

et al. 2002

American Journal of Physiology-Cell Physiology

127

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Hypoxia-inducible factor-1 (HIF-1), a heterodimeric transcription factor consisting of HIF-1α and HIF-1β subunits, controls the expression of a large number of genes involved in the regulation of cellular responses to reduced oxygen availability. The oxygen-regulated subunit, HIF-1α, is stabilized in cells exposed to hypoxia. The regulation of hypoxic responses by nitric oxide (NO) is believed to have wide pathophysiological relevance, thus we investigated whether NO affects HIF-1 activation in hypoxic cells. Here we show that NO generated from NO donors prevented HIF-1α hypoxic accumulation in Hep 3B and PC-12 cells. Addition of a glutathione analog or peroxynitrite scavengers prevented the NO-induced inhibition of HIF-1α accumulation in both cell lines. Exposure to NO was associated with inhibition of mitochondrial electron transport and compensatory glycolysis, which maintained normal cellular ATP content. Succinate, a Krebs cycle intermediate and respiratory chain substrate, restored HIF-1α hypoxic induction in the cells, suggesting involvement of mitochondria in regulation of HIF-1α accumulation during hypoxia. Regulation of HIF-1α by NO is an additional important mechanism by which NO might modulate cellular responses to hypoxia in mammalian cells.

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Continuous exposure to high concentrations of nitric oxide leads to persistent inhibition of oxygen consumption by J774 cells as well as extraction of oxygen by the extracellular medium

Cited by 25 publications

References 19 publications

Inhibition of mitochondrial respiration by endogenous nitric oxide: A critical step in Fas signaling

Inhibition of mitochondrial respiration by endogenous nitric oxide: A critical step in Fas signaling

Renal Antioxidant Status in Rats with Hypertension Induced by N Sup Omega Nitro-<i>L</i>-Arginine Methyl Ester

Role of nitric oxide in the regulation of HIF-1α expression during hypoxia

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