Mouse embryonic fibroblasts from CD38 knockout mice are resistant to oxidative stresses through inhibition of reactive oxygen species production and Ca2+ overload

Academic Article

Abstract

  • CD38 is a multifunctional enzyme that has both ADP-ribosyl cyclase and cADPR hydrolase activities, being capable of cleaving NAD to cyclic ADP ribose (cADPR) and hydrolyzing cADPR to ADPR. It has been reported that there is markedly a reduction of cADPR and elevation of NAD in many tissues from CD38 knockout (CD38 ) mice. Cyclic ADPR is a potent second messenger for intracellular Ca mobilization, and NAD is a key cellular metabolite for cellular energetic and a crucial regulator for multiple signaling pathways in cells. We hypothesize that CD38 knockout may have a protective effect in oxidative stresses through elevating NAD and decreasing cADPR. In the present study, we observed that the mouse embryonic fibroblasts (MEFs) from CD38 mice were significantly resistant to oxidative stress such as H O injury and hypoxia/reoxygenation compared with wild type MEFs (WT MEFs). We further found that production of reactive oxygen species (ROS) and concentrations of intracellular Ca ([Ca ] ) in CD38 MEFs were markedly reduced compared with WT MEFs during hypoxia/reoxygenation. Coincidence with these results, a remarkably lower mRNA level of Nox1, one of the enzymes responsible for ROS generation, was observed in CD38 MEFs. Furthermore, we found that transcription of Nox1 mRNA in WT MEFs could be elevated by calcium ionophore ionomycin in a dose-dependent manner, indicating that the expression of Nox1 mRNA can be regulated by elevation of intracellular [Ca ]. Therefore we concluded that CD38 MEFs are resistant to oxidative stresses through inhibiting intracellular Ca overload and ROS production which may be regulated by Ca -mediated inhibition of Nox1 expression. Our data should provide an insight for elucidating the roles of CD38 in oxidative stresses and a novel perspective of dealing with the ischemia/reperfusion-related diseases. © 2010 Elsevier Inc. + -/- 2+ -/- 2+ 2+ -/- -/- 2+ -/- 2+ 2+ 2 2 i
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    Author List

  • Ge Y; Jiang W; Gan L; Wang L; Sun C; Ni P; Liu Y; Wu S; Gu L; Zheng W
  • Start Page

  • 167
  • End Page

  • 172
  • Volume

  • 399
  • Issue

  • 2