title: The protective effects of propofol against CoCl2-induced HT22 cell hypoxia injury via PP2A/CAMKIIα/nNOS pathway.
abstract: Perioperative cerebral ischemia/hypoxia could induce hippocampal injury and has been reported to induce cognitive impairment. In this study, we used cobalt chloride (CoCl2) to build a hypoxia model in mouse hippocampal cell lines. Propofol, a widely used intravenous anesthetic agent, has been demonstrated to have neuroprotective effect. Here, we explored whether and how propofol attenuated CoCl2-induced mouse hippocampal HT22 cell injury.
  
  
  
  Mouse hippocampal HT22 cells were pretreated with propofol, and then stimulated with CoCl2. Cell viability was measured by cell counting kit 8 (CCK8). The effect of propofol on CoCl2-modulated expressions of B-cell lymphoma 2 (Bcl-2), BAX, cleaved caspase 3, phosphatase A2 (PP2A), and the phosphorylation of Ca2+/Calmodulin (CaM)-dependent protein kinase II (pCAMKIIα), neuron nitric oxide synthase at Ser1412(pnNOS-Ser1412), neuron nitric oxide synthase at Ser847(pnNOS-Ser847) were detected by Western blot analysis.
  
  
  
  Compared with control, CoCl2treatment could significantly decrease cell viability, which could be reversed by propofol. Further, we found CoCl2treatment could up-regulate the expression of PP2A, BAX, cleaved caspase three and cause the phosphorylation of nNOS-Ser1412, but it down-regulated the expression of Bcl-2 and the phosphorylation of CAMKIIα and nNOS-Ser847. More importantly, these CoCl2-mediated effects were attentuated by propofol. In addition, we demonstrated that propofol could exert similar effect to that of the PP2A inhibitor (okadaic acid). Further, the PP2A activator (FTY720) and the CAMKIIα inhibitor (KN93) could reverse the neuroprotective effect of propofol.
  
  
  
  Our data indicated that propofol could attenuate CoCl2-induced HT22 cells hypoxia injury via PP2A/CAMKIIα/nNOS pathway.
authors.affiliation: Department of Anesthesiology, Fudan University Shanghai Cancer Centre, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology, Fudan University Shanghai Cancer Centre, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China.|Department of Medical Oncology, Fudan University Shanghai Cancer Centre, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Lin
authors.affiliation: Department of Anesthesiology, Fudan University Shanghai Cancer Centre, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China.
authors.forename: Jiaqiang
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Fudan University Shanghai Cancer Centre, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China.
authors.forename: Minmin
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology, Fudan University Shanghai Cancer Centre, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China. jiawei_chen@hotmail.com.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China. jiawei_chen@hotmail.com.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Fudan University Shanghai Cancer Centre, No. 270 DongAn Road, Shanghai, 200032, People's Republic of China. anesthesiology2009@hotmail.com.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China. anesthesiology2009@hotmail.com.
authors.forename: Changhong
authors.initials: C
authors.lastname: Miao
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D053148:Caspase 3 / Q000096:biosynthesis; D015687:Cell Hypoxia / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003035:Cobalt; D015870:Gene Expression / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: C494827:Bax protein, mouse; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D003035:Cobalt; D052248:Nitric Oxide Synthase Type I; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D054648:Protein Phosphatase 2; D053148:Caspase 3; C018021:cobaltous chloride; D015742:Propofol
keywords: Cognitive impairment; HT22; Hypoxia; Propofol