Kip Sertac N, Strehler Emanuel E
Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 200 First Street S.W., Rochester, MN 55905, USA.
Ann N Y Acad Sci. 2007 Mar;1099:436-9. doi: 10.1196/annals.1387.005.
Na+/Ca2+ exchangers (NCXs) and plasma membrane Ca2+ pumps (PMCAs) are crucial for intracellular Ca2+ homeostasis and Ca2+ signaling. Elevated [Ca2+]i is a hallmark of neurodegenerative disease and stroke. Here we studied the short-term effect of oxidative stress on the plasma membrane Ca2+ extrusion systems in hippocampal neurons (HN) and found that after 2-3 h exposure to 300 microM H2O2, all NCXs and PMCAs were significantly downregulated at the RNA (NCX) and protein (PMCA) level. Rapid internalization and aggregation of the PMCA was also observed. Our data show that the plasma membrane calcium extrusion systems are sensitive early targets of neurotoxic oxidative stress.
钠钙交换体(NCXs)和质膜钙泵(PMCAs)对于细胞内钙稳态和钙信号传导至关重要。细胞内钙离子浓度升高是神经退行性疾病和中风的一个标志。在此,我们研究了氧化应激对海马神经元(HN)质膜钙外排系统的短期影响,发现暴露于300微摩尔过氧化氢2 - 3小时后,所有的钠钙交换体在RNA水平(NCX)以及质膜钙泵在蛋白质水平(PMCA)均显著下调。还观察到质膜钙泵的快速内化和聚集。我们的数据表明,质膜钙外排系统是神经毒性氧化应激早期的敏感靶点。