title: Angiotensin II-induced mouse hippocampal neuronal HT22 cell apoptosis was inhibited by propofol: Role of neuronal nitric oxide synthase and metallothinonein-3.
abstract: BACKGROUND
  The activation of renin angiotensin system is involved in multiple pathological processes. The neuroprotective effect of propofol has been reported. We hypothesized that propofol may attenuate Angiotensin II (Ang II)-induced apoptosis in mouse hippocampal HT22 cells and aimed to identify the underlying mechanisms.
  
  
  METHODS
  Mouse hippocampal HT22 cells were pre-treated with propofol, and stimulated with Ang II. Apoptosis was examined by transferase dUTP nick end labeling (TUNEL) staining and caspase-3 activity assay. The effect of propofol on Ang II-modulated neuronal nitric oxide synthase (nNOS) expression, nitric oxide (NO) production, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression and activity, caspase activity and metallothinonein-3 (MT-3) expression were measured.
  
  
  RESULTS
  Compared with control, Ang II concentration- and time-dependently induced apoptosis, which was attenuated by propofol in a concentration-dependent manner. Ang II (1 μM, 3 h) induced the expression of nNOS and NADPH oxidase, caused NO and superoxide anion accumulation, thus leading to excessive oxidative stress. Ang II also induced cytochrome C release and the activation of caspase 9 as well as caspase 3. In addition, Ang II reduced the expression of MT-3. Importantly, these effects were alleviated by 50 μM propofol, nNOS inhibitor S-methyl-l-thiocitrulline (SMTC) and angiotensin type 1 receptor (AT1R) blocker losartan, but not AT2R blocker PD123319.
  
  
  CONCLUSIONS
  Ang II via AT1R induced oxidative stress and apoptosis in hippocampal HT22 cells, and the neuroprotective anti-apoptotic effect of propofol was mediated through inhibiting oxidative stress.
authors.affiliation: Department of Anesthesiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai 200032, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai 200032, PR China.
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai 200032, PR China.
authors.forename: M
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai 200032, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai 200032, PR China.
authors.forename: P
authors.initials: P
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, No. 270 DongAn Road, Shanghai 200032, PR China. Electronic address: miaochh@aliyun.com.
authors.forename: C
authors.initials: C
authors.lastname: Miao
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002461:Cell Line, Transformed; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology; D020287:In Situ Nick-End Labeling; D000090023:Metallothionein 3; D051379:Mice; D019255:NADPH Oxidases / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D000090023:Metallothionein 3; C000715430:Mt3 protein, mouse; D009419:Nerve Tissue Proteins; D014662:Vasoconstrictor Agents; D013481:Superoxides; D000804:Angiotensin II; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D019255:NADPH Oxidases; D020169:Caspases
keywords: angiotensin II; apoptosis; metallothinonein-3; nitric oxide synthase; propofol