|
|
N-acetyl-L-cysteine Protect BMCSs Against Apoptosis Induced by H2O2 Via Regulaing the Activity of PI3K-Akt Signaling Pathways |
XIE Rong-hui1,2, YIN Chang-chang3, YIN Ming1, CHEN Wei-cai1, WU Ya-hua3, HE Ding-wen1,2, LIN Si-wen1,2, GENG Shu-guo1,2 |
1 The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China; 2 Nanchang University Graduate School of Medicine, Nanchang 330006, China; 3 Jiujiang University, Jiujiang 332000, China |
|
|
Abstract Objective: To study whether the N-acetyl cysteine (NAC) has direct cytoprotective effects on bone marrow mesenchymal stem cells (BMSCs) against apoptosis induced by H2O2 and and if the PI3K-Akt has partticipated in the mechanism of anti-apoptosis.Methods: BMSCs were extracted from SD rats and cultured by whole bone marrow adherence method. cultured cells were randomly divided into normal control group, H2O2 treatment group, the NAC group, NAC + H2O2 group and LY294002 intervention group. Then the cellular morphology was observed under inverted phase contrast microscope; Cell survival rate of BMSCs was determined by MTT assay in the different concentration of H2O2 and NAC; The apoptosis rate of BMSCs was detected by flow cytometry;the expressions of p-Akt and Akt were analyzed by Western blot.Results The apoptosis of BMSCs could be induced by H2O2,its cell survival rate occurred coincident with H2O2 concentrations,and its morphology appears typical apoptotic characteristic.Compared with H2O2 group,the rate of apoptosis between normal control group and NAC+H2O2 group were lower;but in LY294002 intervention group,its rate of apoptosis was higher and has no significant difference as compared with that of H2O2 group;Compared with normal group, NAC could increase the expression levels of p-Akt and be related to time of exposure; Compared: with H2O2 group,the expression of p-Akt increased,there was no significant difference between H2O2 group and LY294002 intervention group.Conclusion: N-acetyl-L-cysteine can protect the BMCSs against apoptosis induced by H2O2 via the activation of PI3K-Akt signaling pathways.
|
Received: 28 August 2013
Published: 25 November 2013
|
|
|
|
[1] Chen J, Baydoun A R, Xu R, et al. Lysophosphatidic acid protects mesenchymal stem cells against hypoxia and serum deprivation-induced apoptosis. Stem Cells, 2008, 26:135-145. [2] De Flora S, Izzotti A, D'Agostini F, et al.Mechanism of N-acetyl-cysteine in the prevention of DNA damage and cancer, with special reference to smoking-related end-points. Carcinogenesis, 2001, 22(7): 999. [3] 何丁文, 殷明, 殷嫦嫦, 等. Wnt/β-catenin信号通路在大鼠BMSCs神经分化中的作用研究.中国生物工程杂志, 2013, 33(3):61-67. He D W, Yin C C, Yin M, et al.Wnt/β-catenin signaling pathway in neuronal differentiated of rat BMSCs.China Biotechnlogy, 2013, 33(3):61-67. [4] 何丁文, 殷嫦嫦, 殷明, 等. bFGF和EGF诱导大鼠骨髓间充质干细胞分化成神经样细胞.基础医学与临床, 2013, 33(4):444-449. He D W, Yin CH CH, Yin M, et al.Differentiation of rat bone marrow mesenchymal stem cells into neural-like cells induced by bFGF and EGF. Basic&Clinical Medicine, 2013, 33(4):444-449. [5] Matsui T, Li L, Fukui Y, et al.Adenoviral gene transfer of activated phosphatidylinositol 3'-kinase and Akt inhibits apoptosis of hypoxic cardiomyocytes in vitro. Circulation, 1999, 100:2373-2379. [6] Zhu W, Chen J, Cong X, et al.Hypoxia and serum deprivation-induced apoptosis in mesenchymal stem cells. Stem Cells, 2006, 24:416-425. [7] Maddika S, Ande S R, Panigrahi, et al.Cell survival, cell dealth and cycle pathways are interconnected:implications for cancer therapy.Drug Resist Update, 2007, 10:13-29. [8] Stambolic V, Woodgett J R, Functional distinctions of protein kinase B/Akt isoforms defined by their influence on cell migration. Trends Cell Biol, 2006, 16:461-466. [9] Liu A M, Jiang J, Gui C, et al.Angiopietin-I protects mesenchymal stem cells against serum deprivation and hypoxia-induced apoptosis through the PI3K/pathway.Acta Pharmacologica Sinnica, 2008, 29:815-822. [10] Martelli A M, Faenza I, Billi AM, et al.Intranuclear 3, -phosphoinositide metabolism and Akt signaling: new mechanisms for tumorigeneisi and protection against apoptosis. Cellular Signalling, 2006, 18:1101-1107. [11] Wu J, Ding WG, Matsuura H, et al.Inhibitory actions of the phosphatidylinositol 3-kinase inhibitor LY294002 on the human Kvl.5 channel.Br J Pharmacol, 2009, 156(2):377-387. |
|
Viewed |
|
|
|
Full text
|
|
|
|
|
Abstract
|
|
|
|
|
Cited |
|
|
|
|
|
Shared |
|
|
|
|
|
Discussed |
|
|
|
|