title: Heat shock protein 70 protects PC12 cells against ischemia-hypoxia/reoxygenation by maintaining intracellular Ca(2+) homeostasis.
abstract: 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.
authors.affiliation: Department of Intensive Care Unit, Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao, Shandong Province, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Intensive Care Unit, Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao, Shandong Province, China.
authors.forename: Xue-Chun
authors.initials: XC
authors.lastname: Wang
authors.affiliation: Department of Intensive Care Unit, Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao, Shandong Province, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of Intensive Care Unit, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, China.
authors.forename: Shu-Ran
authors.initials: SR
authors.lastname: Huang
authors.affiliation: Department of Intensive Care Unit, Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao, Shandong Province, China.
authors.forename: Qing-Shu
authors.initials: QS
authors.lastname: Li
authors.affiliation: Department of Intensive Care Unit, Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao, Shandong Province, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Intensive Care Unit, Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao, Shandong Province, China.
authors.forename: Yan
authors.identifier: 0000-0003-1166-055X
authors.initials: Y
authors.lastname: Qu
keywords: Ca2+; PC12 cells; endoplasmic reticulum; exogenous heat shock protein 70; inositol 1,4,5-trisphosphate receptor; ischemia-hypoxia/reoxygenation; lentivirus transfection; nerve regeneration; neural regeneration; sarcoplasmic/endoplasmic reticulum Ca2+-ATPase