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

被引：35

作者：

Ge, Yan ^{[1
]}

Jiang, Wei ^{[1
]}

Gan, Lu ^{[1
]}

Wang, Lijun ^{[1
]}

Sun, Changyan ^{[1
]}

Ni, Peiyan ^{[1
]}

Liu, Yin ^{[1
]}

Wu, Sisi ^{[1
]}

Gu, Lunda ^{[1
]}

Zheng, Wei ^{[1
]}

Lund, Frances E. ^{[2
]}

Xin, Hong-Bo ^{[1
,3
]}

机构：

[1] Sichuan Univ, Lab Cardiovasc Dis, W China Hosp, State Key Lab Biotherapy, Chengdu 610041, Peoples R China

[2] Univ Rochester, Sch Med & Dent, Rochester, NY 14642 USA

[3] Nanchang Univ, Inst Translat Med, Nanchang 330031, Peoples R China

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2010年 / 399卷 / 02期

基金：

中国国家自然科学基金;

关键词：

CD38; ROS; Nox1; ca(2+); NADPH OXIDASES; CD38/ADP-RIBOSYL CYCLASE; CALCIUM OVERLOAD; NOX FAMILY; ADP; STREPTOZOTOCIN; ISCHEMIA; INJURY; HEART; METABOLISM;

D O I：

10.1016/j.bbrc.2010.07.040

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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 Ca2+ 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 H2O2 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 Ca2+ ([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 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 [Ca2+]. Therefore we concluded that CD38(-/-) MEFs are resistant to oxidative stresses through inhibiting intracellular Ca2+ overload and ROS production which may be regulated by Ca2+-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. (c) 2010 Elsevier Inc. All rights reserved.

引用

页码：167 / 172

页数：6

共 36 条

[1]

Regulation of SIRT 1 mediated NAD dependent deacetylation: A novel role for the multifunctional enzyme CD38 [J].