Regulation of the cell cycle under anoxia stress in tail muscle and hepatopancreas of the freshwater crayfish, Orconectes virilis

• Published in: Comparative biochemistry and physiology. Part A, Molecular & integrative physiology Molecular & integrative physiology, 2022-07, Vol.269, p.111215-111215, Article 111215
• Main Authors: Singh, Gurjit, Storey, Kenneth B.
• Format: Article
• Language: English
• Subjects: Check point kinase; Cyclin; Cyclin dependent kinase; Cyclin kinase inhibitor; E2F1; Oxygen deprivation; Phosphorylation; Retinoblastoma protein
• ISSN: 1095-6433; 1531-4332
• DOI: 10.1016/j.cbpa.2022.111215

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. [Display omitted] •Anoxic expression of key proteins of the cell cycle suggests overall progression.•Transition from G1➔S & G2➔M phase is driven by cyclins & CDKs despite energy stress.•Increased phosphorylation of Rb(S780) & E2F1 nuclear content aids phase transitions.•Checkpoint kinases & cell cycle inhibitors levels depict partial hold to cell cycle.