Keeley 2018 FASEB J
Keeley TP, Siow RCM, Jacob R, Mann GE (2018) Reduced SERCA activity underlies dysregulation of Ca2+ homeostasis under atmospheric O2 levels. https://doi.org/10.1096/fj.201700685RRR |
Β» FASEB J 32:2531-8. PMID: 29273673 Open Access
Keeley TP, Siow RCM, Jacob R, Mann GE (2018) FASEB J
Abstract: Unregulated increases in cellular Ca2+ homeostasis are a hallmark of pathophysiological conditions and a key trigger of cell death. Endothelial cells cultured under physiologic O2 conditions (5% O2) exhibit a reduced cytosolic Ca2+ response to stimulation. The mechanism for reduced plateau [Ca2+]i upon stimulation was due to increased sarco/endoplasmic reticulum Ca2+ ATPase (SERCA)-mediated reuptake rather than changes in Ca2+ influx capacity. Agonist-stimulated phosphorylation of the SERCA regulatory protein phospholamban was increased in cells cultured under 5% O2. Elevation of cytosolic and mitochondrial [Ca2+] and cell death after prolonged ionomycin treatment, as a model of Ca2+ overload, were lower when cells were cultured long-term under 5% compared with 18% O2. This protection was abolished by cotreatment with the SERCA inhibitor cyclopiazonic acid. Taken together, these results demonstrate that culturing cells under hyperoxic conditions reduces their ability to efficiently regulate [Ca2+]i, resulting in greater sensitivity to cytotoxic stimuli.-Keeley, T. P., Siow, R. C. M., Jacob, R., Mann, G. E. Reduced SERCA activity underlies dysregulation of Ca2+ homeostasis under atmospheric O2 levels.
β’ Bioblast editor: Gnaiger E
Labels:
Stress:Hypoxia
Preparation: Intact cells
Regulation: Calcium
MitoFit2022Hypoxia