Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario K1S 5B6, Canada. Electronic address: https://twitter.com/GurjitS92273426.
Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario K1S 5B6, Canada.
Comp Biochem Physiol A Mol Integr Physiol. 2022 Jul;269:111215. doi: 10.1016/j.cbpa.2022.111215. Epub 2022 Apr 13.
Regulation of the cell cycle is an understudied response to oxygen deprivation among crustaceans. The virile crayfish, Orconectes virilis, is a freshwater crustacean that when challenged by environmental oxygen limitation undergoes metabolic rate depression (to ~30% of normal levels) and switches to anaerobic metabolism to generate energy. To understand how crayfish regulate the cell cycle in response to anoxia, key proteins involved in cell cycle control were analyzed in muscle and hepatopancreas. At the G1/S barrier, an overall upregulation of positive regulators of cell cycle progression was indicated by the responses of G1 cyclins (cyclin D and cyclin E) and Cyclin dependent kinases (CDK4, CDK6 and CDK2) under anoxia. Although the levels of Cyclin kinase inhibitors (CKIs) at this juncture were also upregulated (P15/16 and P21 (T145) in muscle and P16 (S152) in hepatopancreas), levels of a major regulator of this phase and driver to S-phase, E2F1, were significantly higher in both tissues in conjunction with deactivation of its inhibitor, Retinoblastoma (Rb) protein. At the G2/M barrier, expression profiles of the G2 cyclin B suggested cell cycle progression despite overall trend of higher activities of checkpoint kinases, (Chk1 (S317) and Chk2 (S19)), that also negatively regulate the cyclin B-CDK1 complex via CdC25C (cell division cycle 25) whose levels remained unchanged. Overall, the present study suggests continued cell cycle progression, albeit with potential deceleration, as indicated by checkpoint kinases and kinase inhibitor profiles that might play a role in protecting tissues from apoptotic damage under chronic anoxic stress.
甲壳动物对缺氧的细胞周期调控研究较少。雄性十足目螯虾，即美洲红点鲑，是一种淡水甲壳动物，当受到环境缺氧的挑战时，会经历代谢率下降（降至正常水平的 30%左右），并切换为无氧代谢以产生能量。为了了解螯虾如何调节细胞周期以应对缺氧，对肌肉和肝胰腺中参与细胞周期控制的关键蛋白进行了分析。在 G1/S 检查点，细胞周期正调控因子的反应表明，G1 期周期蛋白（周期蛋白 D 和周期蛋白 E）和细胞周期蛋白依赖性激酶（CDK4、CDK6 和 CDK2）在缺氧条件下整体上调。尽管在这个节点上细胞周期蛋白激酶抑制剂（CKI）的水平也上调（肌肉中的 P15/16 和 P21（T145）以及肝胰腺中的 P16（S152）），但此阶段的主要调节因子和 S 期驱动因子 E2F1 的水平在这两种组织中都显著升高，同时其抑制剂视网膜母细胞瘤（Rb）蛋白失活。在 G2/M 检查点，G2 期周期蛋白 B 的表达谱表明细胞周期继续进展，尽管总体上检查点激酶（Chk1（S317）和 Chk2（S19））的活性更高，它们也通过 CdC25C（细胞分裂周期 25）负调控周期蛋白 B-CDK1 复合物，而 CdC25C 的水平保持不变。总的来说，本研究表明尽管存在潜在的减速，但细胞周期仍在继续推进，这可以通过检查点激酶和激酶抑制剂的表达谱来表明，它们可能在慢性缺氧应激下保护组织免受凋亡损伤方面发挥作用。
