SUMO proteins are involved in the stress response during spermatogenesis and are localized to DNA double-strand breaks in germ cells
SUMO proteins are involved in the stress response during spermatogenesis and are localized to DNA double-strand breaks in germ cells
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DOI：
10.1530/rep-09-0492
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发表时间：
2010-06-01
期刊：
影响因子：
3.8
通讯作者：
Vigodner, Margarita
中科院分区：
文献类型：
--
作者：
Shrivastava, Vibha;Pekar, Marina;Vigodner, Margarita
小泛素样修饰物(SUMO)蛋白在不同组织中与细胞应激反应有关，但目前尚不清楚SUMO在精子发生过程中是否具有类似的作用。在这项研究中，监测了在不同类型的细胞应激诱导前后，游离相扑亚型和高分子量(HMW)相扑结合物水平的变化。利用从小鼠睾丸中分离的细胞系和原代细胞，在短期暴露于热应激和氧化应激后，检测到SUMO1和SUMO2/3结合物的水平发生了显著变化。高浓度的H_2O_2使蛋白质的总甲基化增加，而低浓度的H_2O_2主要引起蛋白质的去甲基化。免疫荧光研究将相扑定位于应激生殖细胞和减数分裂重组过程中DNA双链断裂的位置。为了研究体内氧化应激的影响，采用了暴露于烟草烟雾12周的动物。烟草暴露小鼠体内HMW蛋白总甲基化的变化与其氧化损伤的变化是一致的。我们的结果与不同相扑亚型在生殖细胞应激反应中的重要作用是一致的。此外，本研究还证实了拓扑异构酶2a是正常精子发生和应激状态下苏莫化的靶标之一。再生产(2010)139 999-1010
Small ubiquitin-like modifiers (SUMO) proteins have been implicated in cellular stress response in different tissues, but whether sumoylation has a similar role during spermatogenesis is currently unknown. In this study, changes in the levels of both free SUMO isoforms and high-molecular weight (HMW) SUMO conjugates were monitored before and after the induction of different types of cellular stresses. Using cell lines and primary cells freshly isolated from mouse testes, significant changes were detected in the levels of SUMO1 and SUMO2/3 conjugates following short exposure of the cells to heat stress and oxidative stress. While high concentrations of H2O2 caused an increase in protein sumoylation, low concentrations of H2O2 mostly caused protein desumoylation. Immunofluorescence studies localized SUMO to the sites of DNA double-strand breaks in stressed germ cells and during meiotic recombination. To study the effect of oxidative stress in vivo, animals exposed to tobacco smoke for 12 weeks were used. Changes in sumoylation of HMW proteins were consistent with their oxidative damage in the tobacco-exposed mice. Our results are consistent with the important roles of different SUMO isoforms in stress responses in germ cells. Furthermore, this study identified topoisomerase 2 a as one of the targets of sumoylation during normal spermatogenesis and under stress. Reproduction (2010) 139 999-1010