Yoon Jungbin, Park Kyosun, Hwang Deog Su, Rhee Kunsoo
Department of Biological Sciences, Seoul National University, Seoul, Korea.
Mol Reprod Dev. 2017 Mar;84(3):265-274. doi: 10.1002/mrd.22778. Epub 2017 Feb 2.
Mammalian male germ cells are exceptionally labile to heat stress. A temporal arrest of translation is one immediate response to heat, which involves heat-induced phosphorylation of eukaryotic initiation factor 2α (eIF2α) to block the formation of the translational initiation complex. Here, we investigated the protective mechanisms against heat stress in mouse male germ cells. All known eIF2α kinases were expressed in lineage- and developmental stage-specific manners in the testis; noteworthy was the presence of Gcn2 (General control nonderepressible 2 kinase) in spermatocytes of all seminiferous tubules. Multiple eIF2α kinases are likely activated upon heat stress in male germ cells. ISRIB (Integrated stress response inhibitor) was then used to determine the events downstream of eIF2α phosphorylation. ISRIB significantly reduced the rate of stress granule formation in spermatocytes at early-stage (III-IV) seminiferous tubules, and induced a number of apoptotic germ cells at late-stage (XI-XII) seminiferous tubules near the onset of meiosis. Thus, stress granule formation is a downstream event of eIF2α phosphorylation that may not directly protect cells from apoptosis, at least in spermatocytes of seminiferous tubules in early stages. Mol. Reprod. Dev. 84: 265-274, 2017. © 2017 Wiley Periodicals, Inc.
哺乳动物雄性生殖细胞对热应激异常敏感。翻译的暂时停滞是对热的一种即时反应，这涉及到热诱导的真核起始因子2α（eIF2α）磷酸化，以阻止翻译起始复合物的形成。在此，我们研究了小鼠雄性生殖细胞中针对热应激的保护机制。所有已知的eIF2α激酶在睾丸中以谱系和发育阶段特异性的方式表达；值得注意的是，所有生精小管的精母细胞中都存在Gcn2（一般控制非抑制性2激酶）。热应激时，雄性生殖细胞中可能有多种eIF2α激酶被激活。然后使用ISRIB（综合应激反应抑制剂）来确定eIF2α磷酸化下游的事件。ISRIB显著降低了早期（III-IV期）生精小管精母细胞中应激颗粒的形成率，并在减数分裂开始附近的晚期（XI-XII期）生精小管中诱导了许多凋亡的生殖细胞。因此，应激颗粒的形成是eIF2α磷酸化的下游事件，至少在早期生精小管的精母细胞中，它可能不会直接保护细胞免于凋亡。《分子生殖与发育》84: 265 - 274, 2017。© 2017威利期刊公司。
