Roles of NAD+, PARP-1, and Sirtuins in Cell Death, Ischemic Brain Injury, and Synchrotron Radiation X-Ray-Induced Tissue Injury
Open Access
- 10 December 2013
- journal article
- review article
- Published by Hindawi Limited in Scientifica
- Vol. 2013, 1-11
- https://doi.org/10.1155/2013/691251
Abstract
NAD+plays crucial roles in a variety of biological processes including energy metabolism, aging, and calcium homeostasis. Multiple studies have also shown that NAD+administration can profoundly decrease oxidative cell death and ischemic brain injury. A number of recent studies have further indicated that NAD+administration can decrease ischemic brain damage, traumatic brain damage and synchrotron radiation X-ray-induced tissue injury by such mechanisms as inhibiting inflammation, decreasing autophagy, and reducing DNA damage. Our latest study that applies nano-particles as a NAD+carrier has also provided first direct evidence demonstrating a key role of NAD+depletion in oxidative stress-induced ATP depletion. Poly(ADP-ribose) polymerase-1 (PARP-1) and sirtuins are key NAD+-consuming enzymes that mediate multiple biological processes. Recent studies have provided new information regarding PARP-1 and sirtuins in cell death, ischemic brain damage and synchrotron radiation X-ray-induced tissue damage. These findings have collectively supported the hypothesis that NAD+metabolism, PARP-1 and sirtuins play fundamental roles in oxidative stress-induced cell death, ischemic brain injury, and radiation injury. The findings have also supported “the Central Regulatory Network Hypothesis”, which proposes that a fundamental network that consists of ATP, NAD+and Ca2+as its key components is the essential network regulating various biological processes.Keywords
Funding Information
- National Key Basic Research (2010CB834306, 81171098, 81271305)
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