engleski

Pyridine Nucleotides in Regulation of Cell Death and Survival by Redox and Non-Redox Reactions

Changes of the level and ratios of pyridine nucleotides determine metabolism- dependent cellular redox status and the activity of poly(ADP-ribose) polymerases (PARPs) and sirtuins, thereby influencing several processes closely related to cell survival and death. Pyridine nucleotides participate in numerous metabolic reactions whereby their net cellular level remains constant, but the ratios of NAD+/NADP+ and NADH/NADPH oscillate according to metabolic changes in response to diverse stress signals. In non-redox reactions, NAD+ is degraded and quickly, afterwards, resynthesized in NAD+ salvage pathway, unless overwhelming activation of PARP-1 consumes NAD+ to the point of no return, when cell can no longer generate enough ATP to accommodate NAD+ resynthesis. The activity of PARP-1 is mandatory for the onset of cytoprotective autophagy upon sublethal stress signals. It has become increasingly clear that redox status, largely influenced by the metabolism-dependent composition of pyridine nucleotides pool, plays an important role in the synthesis of pro-apoptotic and anti- apoptotic sphingolipids. Awareness of the involvement of the prosurvival sphingolipid, sphingosine-1-phosphate, in transition from inflammation to malignant transformation has recently emerged. Here, the participation of pyridine nucleotides in redox- and non-redox reactions, sphingolipid metabolism, and their role in cell fate decisions is reviewed.

pyridine nucleotide ; oxidative stress ; energy metabolism ; poly(ADP-ribose) polymerase ; sirtuin ; sphingolipid

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