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• W4309726377 endingPage "35" @default.
• W4309726377 startingPage "22" @default.
• W4309726377 abstract "Limited O2 availability can decrease essential processes in energy metabolism. However, cancers have developed distinct metabolic adaptations to these conditions. For example, glutaminolysis can maintain energy metabolism and hypoxia signaling. Additionally, it has been observed that nitric oxide (NO) possesses concentration-dependent, biphasic effects in cancer. NO has potent anti-tumor effects through modulating events such as angiogenesis and metastasis at low physiological concentrations and inducing cell death at higher concentrations. In this study, Ewing Sarcoma cells (A-673), MIA PaCa, and SKBR3 cells were treated with DetaNONOate (DetaNO) in a model of hypoxia (1% O2) and reoxygenation (21% O2). All 3 cell types showed NO-dependent inhibition of cellular O2 consumption which was enhanced as O2-tension decreased. L-Gln depletion suppressed the mitochondrial response to decreasing O2 tension in all 3 cell types and resulted in inhibition of Complex I activity. In A-673 cells the O2 tension dependent change in mitochondrial O2 consumption and increase in glycolysis was dependent on the presence of L-Gln. The response to hypoxia and Complex I activity were restored by α-ketoglutarate. NO exposure resulted in the A-673 cells showing greater sensitivity to decreasing O2 tension. Under conditions of L-Gln depletion, NO restored HIF-1α levels and the mitochondrial response to O2 tension possibly through the increase of 2-hydroxyglutarate. NO also resulted in suppression of cellular bioenergetics and further inhibition of Complex I which was not rescued by α-ketoglutarate. Taken together these data suggest that NO modulates the mitochondrial response to O2 differentially in the absence and presence of L-Gln. These data suggest a combination of metabolic strategies targeting glutaminolysis and Complex I in cancer cells." @default.
• W4309726377 created "2022-11-29" @default.
• W4309726377 creator A5011003263 @default.
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• W4309726377 creator A5043712619 @default.
• W4309726377 creator A5062506120 @default.
• W4309726377 date "2023-01-01" @default.
• W4309726377 modified "2023-10-14" @default.
• W4309726377 title "Glutamine-dependent effects of nitric oxide on cancer cells subjected to hypoxia-reoxygenation" @default.
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• W4309726377 doi "https://doi.org/10.1016/j.niox.2022.11.003" @default.
• W4309726377 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36414197" @default.

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