A critical role of PUMA in maintenance of genomic integrity of murine spermatogonial stem cell precursors after genotoxic stress  

作　　者：Anne Forand 

机构地区：[1]CEA, DSV, iRCM, SCSR, Laboratory of Differentiation and Radiobiology of the Gonads, Fontenay aux Roses F-92265, France [2]Universite Paris 7 Denis Diderot, Unit of Gametogenesis and Genotoxicity, Fontenay aux Roses F-92265, France [3]INSERM, U566, Fontenay aux Roses F-92265, France

出　　处：《Cell Research》2009年第8期1018-1030,共13页细胞研究（英文版）

摘　　要：Neonatal gonocytes are precursors of spermatogonial stem cells. Preserving their integrity by elimination of damaged germ cells may be crucial to avoid the transmission of genetic alterations to progeny. Using 7-irradiation, we investigated by immunohistochemistry, flow cytometry and real-time PCR components of the death machinery in neonatal gonocytes. Their death was correlated with caspase 3 activation but not with AIF translocation into the nu- cleus. The in vivo contribution of both the extrinsic and the intrinsic pathways was then investigated. We focused on the roles of TRAIL/Death Receptor 5 （DR5） and PUMA. Our results were validated using knockout mice. Whereas DR5 expression was upregulated at the cell surface after radiation, caspase 8 was not activated. However, we detected caspase 9 cleavage associated with cytochrome c release. In mice deficient for PUMA, radiation-induced gonocyte apoptosis was reduced, whereas invalidation of TRAIL had no effect. Overall, our results show that genotoxic stressinduced apoptosis of gonocytes is caspase-dependent and involves almost exclusively the intrinsic pathway. Furthermore, PUMA plays a critical role in the maintenance of genomic integrity of spermatogonial stem cell precursors.

关 键 词：cell death GONOCYTE PUMA apoptosis CASPASE radiation 

分 类 号：Q954.434[生物学—动物学] Q593.2