CD38 plays key roles in both antioxidation and cell survival of H2O2-treated primary rodent astrocytes.

CD38 is an ecto-enzyme that consumes NAD+ to produce cyclic ADP-ribose (cADPR) --- a potent agonist of ryanodine receptors. Recent studies have suggested CD38 may play significant roles in both ischemic brain injury and traumatic brain injury, while the mechanisms underlying the roles of CD38 in neurological diseases remain unclear. Because oxidative stress plays key roles in both ischemic brain damage and traumatic brain damage, in this study we used primary astrocyte cultures as a experimental model to test our hypothesis that CD38 may play significant roles in oxidative stress-induced neural cell death. We found CD38 siRNA-produced decrease in CD38 levels can lead to a significant increase in H2O2-induced astrocyte death. Moreover, the CD38 siRNA treatment can significantly aggravate oxidative stress in the H2O2-treated cells, as indicated by increases in both superoxide and lipid peroxidation, suggesting that CD38 is required for maintaining the antioxidation capacity of the cells. We also found that H2O2 can induce increased CD38 expression. Collectively, our study has obtained novel findings suggesting that CD38 plays a significant role in both antioxidation and cell survival of reactive oxygen species-exposed primary astrocytes, suggesting that CD38 may become a novel target for decreasing the oxidative damage in neurological disorders.