Hydrogen peroxide-induced cellular apoptosis is mediated by TGF-β2 signaling pathway in cultured human lens epithelial cells

被引：5
作者：
Cao X.G. [1 ]
Li X.X. [1 ]
Hu J.X. [2 ]
Bao Y.Z. [1 ]
机构：
[1] Department of Ophthalmology, People's Hospital of Peking University, XiCheng District, Beijing 100044
[2] College of Environmental Sciences, Peking University, Beijing
来源：
International Ophthalmology | 2010年 / 30卷 / 3期
关键词：
Apoptosis; Hydrogen peroxide; Lens epithelial cells; Smad-4; TGF-β2;
D O I：
10.1007/s10792-009-9309-8
中图分类号：
学科分类号：
摘要：
© The objective of this study was to investigate the signaling characteristics of transforming growth factor-β2 (TGF-β2) and the Smads (Caenorhabditis elegans, Sma; Drosophila mothers against dpp, Mad) signal pathway of cellular apoptosis induced by hydrogen peroxide with human lens epithelial cells (HLECs). HLECs were starved for 24 h before exposure to 0.1 μmol/ml of hydrogenperoxide in the presence and in the absence of 0.01 lg/ml of AF-302-NA, a monoclonal anti-TGFbβ neutralization antibody. Non-stimulated cells served as controls. Cell apoptosis was examined by in situ immunocytochemistry using terminal deoxynucleotidyl transferase dUTP-mediated biotin nick end labeling (TUNEL) and by flow cytometry (FCM) using Annexin V-FITC apoptosis detection. Gene expression was assessed using the reverse transcription- polymerase chain reaction (RT-PCR). Smad-4 localization was observed by immunocytochemistry. Hydrogen peroxide induced the accumulation of Smad-4 in the nucleus of HLECs, and upregulated the expression of TGF-β receptors (TβRs) mRNA in HLECs, as well as upregulated the expression of the apoptotic gene bax, which leads HLECs to apoptosis. AF-302-NA decreased cellular apoptosis induced by hydrogen peroxide in HLECs and inhibited the translocation of Smad-4 from the cytoplasm to thecell nucleus. Moreover, AF-302-NA upregulated the expression of TβRs mRNA and downregulated the expression of bax mRNA in HLECs incubated with hydrogen peroxide. Our study demonstrated that the TGF-β2 signal pathway participated in the apoptotic signal transfer and might be an initiator of cellular apoptosis of HLECs after incubation with hydrogen peroxide. Interruption of the TGF-β2 signal pathway could partially protect HLECs from apoptosis induced by incubation with hydrogen peroxide. © Springer Science+Business Media B.V. 2009.
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页码：229 / 237
页数：8
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