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The pentose‐phosphate pathway in neuronal survival against nitrosative stress
Author(s) -
Bolaños Juan P.,
Almeida Angeles
Publication year - 2010
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.280
Subject(s) - pentose phosphate pathway , glycolysis , glutathione , biochemistry , microbiology and biotechnology , chemistry , antioxidant , oxidative stress , reactive oxygen species , biology , enzyme
Neurons are thought to be particularly vulnerable cells against reactive oxygen and nitrogen species (RONS) damage (nitrosative stress), due in part to their weak antioxidant defense and low ability to compensate energy homeostasis. Intriguingly, nitrosative stress efficiently stimulates the rate of the antioxidant pentose‐phosphate pathway (PPP), which generates NADPH a necessary cofactor for the reduction of glutathione disulfide. In fact, inhibition of PPP sensitizes cultured neurons to glutathione oxidation and apoptotic death, whereas its stimulation confers resistance to nitrosative stress. Furthermore, we recently described that neurons can preferentially use glucose through the PPP by inhibiting glycolysis, which is achieved by continuously degrading the glycolytic positive‐effector protein, 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase‐3 (Pfkfb3) by the action of the E3 ubiquitine ligase anaphase‐promoting complex/cyclosome (APC/C) Cdh1 . These results suggest that the antioxidant fragility of neurons may be compensated by the PPP at the expense of inhibiting bioenergetic glycolysis. © 2009 IUBMB IUBMB Life, 62(1):14–18, 2010