Mouse embryonic fibroblasts from CD38 knockout mice are resistant to oxidative stresses through inhibition of reactive oxygen species production and Ca(2+) overload

Biochemical and Biophysical Research Communications
Yan GeHong-Bo Xin

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(2+) 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(2)O(2) 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(2+) ([Ca(2+)](i)) 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 obs...Continue Reading

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Citations

Mar 29, 2014·Oxidative Medicine and Cellular Longevity·Xiu-Jun FuXiong Zhang
Mar 5, 2015·Brain Research Bulletin·Thomas I NathanielAdebobola Imeh-Nathaniel
Aug 1, 2014·American Journal of Respiratory Cell and Molecular Biology·Suengwon LeeJames S K Sham
May 7, 2011·Biochemical and Biophysical Research Communications·Lu GanWei Jiang
Mar 16, 2017·Journal of Cellular and Molecular Medicine·Xiao-Hui GuanHong-Bo Xin
Jan 13, 2018·Molecular Neurobiology·Yongwoo JangSun Wook Hwang

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