Liu Yuan, Wang Xue-Chun, Hu Dan, Huang Shu-Ran, Li Qing-Shu, Li Zhi, Qu Yan
Department of Intensive Care Unit, Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao, Shandong Province, China.
Department of Intensive Care Unit, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, China.
Neural Regen Res. 2016 Jul;11(7):1134-40. doi: 10.4103/1673-5374.187051.
Heat shock protein 70 (HSP70) maintains Ca(2+) homeostasis in PC12 cells, which may protect against apoptosis; however, the mechanisms of neuroprotection are unclear. Therefore, in this study, we examined Ca(2+) levels in PC12 cells transfected with an exogenous lentiviral HSP70 gene expression construct, and we subsequently subjected the cells to ischemia-hypoxia/reoxygenation injury. HSP70 overexpression increased neuronal viability and ATPase activity, and it decreased cellular reactive oxygen species levels and intracellular Ca(2+) concentration after hypoxia/reoxygenation. HSP70 overexpression enhanced the protein and mRNA expression levels of sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA), but it decreased the protein and mRNA levels of inositol 1,4,5-trisphosphate receptor (IP3R), thereby leading to decreased intracellular Ca(2+) concentration after ischemia-hypoxia/reoxygenation. These results suggest that exogenous HSP70 protects against ischemia-hypoxia/reoxygenation injury, at least in part, by maintaining cellular Ca(2+) homeostasis, by upregulating SERCA expression and by downregulating IP3R expression.
热休克蛋白70（HSP70）维持PC12细胞内的Ca(2+)稳态，这可能对细胞凋亡起到保护作用；然而，其神经保护机制尚不清楚。因此，在本研究中，我们检测了转染外源性慢病毒HSP70基因表达构建体的PC12细胞中的Ca(2+)水平，随后对这些细胞进行缺血缺氧/复氧损伤处理。HSP70过表达增加了神经元活力和ATP酶活性，并降低了缺氧/复氧后细胞内活性氧水平和细胞内Ca(2+)浓度。HSP70过表达增强了肌浆网/内质网Ca(2+)-ATP酶（SERCA）的蛋白质和mRNA表达水平，但降低了肌醇1,4,5-三磷酸受体（IP3R）的蛋白质和mRNA水平，从而导致缺血缺氧/复氧后细胞内Ca(2+)浓度降低。这些结果表明，外源性HSP70至少部分地通过维持细胞Ca(2+)稳态、上调SERCA表达和下调IP3R表达来保护细胞免受缺血缺氧/复氧损伤。
