Roles of NAD (+) , PARP-1, and Sirtuins in Cell Death, Ischemic Brain Injury, and Synchrotron Radiation X-Ray-Induced Tissue Injury.

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 Ca(2+) as its key components is the essential network regulating various biological processes.