TY - JOUR
T1 - Interplay between Reactive Oxygen/Reactive Nitrogen Species and Metabolism in Vascular Biology and Disease
AU - Ushio-Fukai, Masuko
AU - Ash, Dipankar
AU - Nagarkoti, Sheela
AU - Belin De Chantemèle, Eric J.
AU - Fulton, David J.R.
AU - Fukai, Tohru
N1 - Funding Information:
This work was supported by NIH R01HL135584 (to M.U.-F.), NIHR01HL116976, NIHR01HL133613, NIH1R01HL147550 (to T.F., M.U.-F.), Department of Veterans Affairs Merit Review grant 2I01BX001232 (to T.F.).
Publisher Copyright:
© Copyright 2021, Mary Ann Liebert, Inc., publishers 2021.
PY - 2021/6/1
Y1 - 2021/6/1
N2 - Reactive oxygen species (ROS; e.g., superoxide [O2•-] and hydrogen peroxide [H2O2]) and reactive nitrogen species (RNS; e.g., nitric oxide [NO•]) at the physiological level function as signaling molecules that mediate many biological responses, including cell proliferation, migration, differentiation, and gene expression. By contrast, excess ROS/RNS, a consequence of dysregulated redox homeostasis, is a hallmark of cardiovascular disease. Accumulating evidence suggests that both ROS and RNS regulate various metabolic pathways and enzymes. Recent studies indicate that cells have mechanisms that fine-tune ROS/RNS levels by tight regulation of metabolic pathways, such as glycolysis and oxidative phosphorylation. The ROS/RNS-mediated inhibition of glycolytic pathways promotes metabolic reprogramming away from glycolytic flux toward the oxidative pentose phosphate pathway to generate nicotinamide adenine dinucleotide phosphate (NADPH) for antioxidant defense. This review summarizes our current knowledge of the mechanisms by which ROS/RNS regulate metabolic enzymes and cellular metabolism and how cellular metabolism influences redox homeostasis and the pathogenesis of disease. A full understanding of these mechanisms will be important for the development of new therapeutic strategies to treat diseases associated with dysregulated redox homeostasis and metabolism. Antioxid. Redox Signal. 34, 1319-1354.
AB - Reactive oxygen species (ROS; e.g., superoxide [O2•-] and hydrogen peroxide [H2O2]) and reactive nitrogen species (RNS; e.g., nitric oxide [NO•]) at the physiological level function as signaling molecules that mediate many biological responses, including cell proliferation, migration, differentiation, and gene expression. By contrast, excess ROS/RNS, a consequence of dysregulated redox homeostasis, is a hallmark of cardiovascular disease. Accumulating evidence suggests that both ROS and RNS regulate various metabolic pathways and enzymes. Recent studies indicate that cells have mechanisms that fine-tune ROS/RNS levels by tight regulation of metabolic pathways, such as glycolysis and oxidative phosphorylation. The ROS/RNS-mediated inhibition of glycolytic pathways promotes metabolic reprogramming away from glycolytic flux toward the oxidative pentose phosphate pathway to generate nicotinamide adenine dinucleotide phosphate (NADPH) for antioxidant defense. This review summarizes our current knowledge of the mechanisms by which ROS/RNS regulate metabolic enzymes and cellular metabolism and how cellular metabolism influences redox homeostasis and the pathogenesis of disease. A full understanding of these mechanisms will be important for the development of new therapeutic strategies to treat diseases associated with dysregulated redox homeostasis and metabolism. Antioxid. Redox Signal. 34, 1319-1354.
KW - metabolism
KW - oxidative stress
KW - reactive nitrogen species
KW - reactive oxygen species
KW - redox signaling
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U2 - 10.1089/ars.2020.8161
DO - 10.1089/ars.2020.8161
M3 - Review article
C2 - 33899493
AN - SCOPUS:85106166871
SN - 1523-0864
VL - 34
SP - 1319
EP - 1354
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
IS - 16
ER -