Phosphoproteomic analysis of the adaption of epididymal epithelial cells to corticosterone challenge.

Autor: Skerrett-Byrne DA; Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, College of Engineering, Science and Environment, The University of Newcastle, Callaghan, NSW, Australia.; Infertility and Reproduction Research Program, Hunter Medical Research Institute, New Lambton Heights, New Lambton, NSW, Australia., Stanger SJ; Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, College of Engineering, Science and Environment, The University of Newcastle, Callaghan, NSW, Australia.; Infertility and Reproduction Research Program, Hunter Medical Research Institute, New Lambton Heights, New Lambton, NSW, Australia., Trigg NA; Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, College of Engineering, Science and Environment, The University of Newcastle, Callaghan, NSW, Australia.; Infertility and Reproduction Research Program, Hunter Medical Research Institute, New Lambton Heights, New Lambton, NSW, Australia., Anderson AL; Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, College of Engineering, Science and Environment, The University of Newcastle, Callaghan, NSW, Australia.; Infertility and Reproduction Research Program, Hunter Medical Research Institute, New Lambton Heights, New Lambton, NSW, Australia., Sipilä P; Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, and Turku Center for Disease Modeling, University of Turku, Turku, Finland., Bernstein IR; Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, College of Engineering, Science and Environment, The University of Newcastle, Callaghan, NSW, Australia.; Infertility and Reproduction Research Program, Hunter Medical Research Institute, New Lambton Heights, New Lambton, NSW, Australia., Lord T; Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, College of Engineering, Science and Environment, The University of Newcastle, Callaghan, NSW, Australia.; Infertility and Reproduction Research Program, Hunter Medical Research Institute, New Lambton Heights, New Lambton, NSW, Australia., Schjenken JE; Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, College of Engineering, Science and Environment, The University of Newcastle, Callaghan, NSW, Australia.; Infertility and Reproduction Research Program, Hunter Medical Research Institute, New Lambton Heights, New Lambton, NSW, Australia., Murray HC; School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW, Australia.; Precision Medicine Research Program, Hunter Medical Research Institute, New Lambton Heights, New Lambton, NSW, Australia., Verrills NM; School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW, Australia.; Precision Medicine Research Program, Hunter Medical Research Institute, New Lambton Heights, New Lambton, NSW, Australia., Dun MD; School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW, Australia.; Precision Medicine Research Program, Hunter Medical Research Institute, New Lambton Heights, New Lambton, NSW, Australia., Pang TY; The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia.; Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, VIC, Australia., Nixon B; Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, College of Engineering, Science and Environment, The University of Newcastle, Callaghan, NSW, Australia.; Infertility and Reproduction Research Program, Hunter Medical Research Institute, New Lambton Heights, New Lambton, NSW, Australia.
Jazyk: angličtina
Zdroj: Andrology [Andrology] 2024 Jul; Vol. 12 (5), pp. 1038-1057. Date of Electronic Publication: 2024 Apr 04.
DOI: 10.1111/andr.13636
Abstrakt: Background: The epididymis has long been of interest owing to its role in promoting the functional maturation of the male germline. More recent evidence has also implicated the epididymis as an important sensory tissue responsible for remodeling of the sperm epigenome, both under physiological conditions and in response to diverse forms of environmental stress. Despite this knowledge, the intricacies of the molecular pathways involved in regulating the adaptation of epididymal tissue to paternal stressors remains to be fully resolved.
Objective: The overall objective of this study was to investigate the direct impact of corticosterone challenge on a tractable epididymal epithelial cell line (i.e., mECap18 cells), in terms of driving adaptation of the cellular proteome and phosphoproteome signaling networks.
Materials and Methods: The newly developed phosphoproteomic platform EasyPhos coupled with sequencing via an Orbitrap Exploris 480 mass spectrometer, was applied to survey global changes in the mECap18 cell (phospho)proteome resulting from sub-chronic (10-day) corticosterone challenge.
Results: The imposed corticosterone exposure regimen elicited relatively subtle modifications of the global mECap18 proteome (i.e., only 73 out of 4171 [∼1.8%] proteins displayed altered abundance). By contrast, ∼15% of the mECap18 phosphoproteome was substantially altered following corticosterone challenge. In silico analysis of the corresponding parent proteins revealed an activation of pathways linked to DNA damage repair and oxidative stress responses as well as a reciprocal inhibition of pathways associated with organismal death. Corticosterone challenge also induced the phosphorylation of several proteins linked to the biogenesis of microRNAs. Accordingly, orthogonal validation strategies confirmed an increase in DNA damage, which was ameliorated upon selective kinase inhibition, and an altered abundance profile of a subset of microRNAs in corticosterone-treated cells.
Conclusions: Together, these data confirm that epididymal epithelial cells are reactive to corticosterone challenge, and that their response is tightly coupled to the opposing action of cellular kinases and phosphatases.
(© 2024 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)
Databáze: MEDLINE
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