title: Mitochondrial-dependent mechanisms are involved in angiotensin II-induced apoptosis in dopaminergic neurons.
abstract: BACKGROUND
  We recently demonstrated that angiotensin II (Ang II) was involved in the etiology of Parkinson's disease (PD) via induction of apoptosis of dopaminergic neurons, but the mechanisms are not completely elucidated. Here, we asked whether mitochondrial-dependent mechanisms contributed to the Ang II-induced dopaminergic neuronal apoptosis.
  
  
  METHODS
  CATH.a cells were incubated with Ang II in combination with mitochondrial permeability transition pore (mPTP) inhibitors or angiotensin receptor antagonists, and apoptosis rate, caspase-3 activity, cytochrome c levels, and mPTP opening were assessed.
  
  
  RESULTS
  We showed that Ang II triggered apoptosis via a mitochondrial-dependent pathway, as elevated cytochrome c levels were observed in the cytosol. By employing cyclosporin A and sanglifehrin A, two specific mPTP inhibitors, we revealed that cytochrome c release from mitochondria into cytoplasm was ascribed to mPTP opening. Meanwhile, the aforementioned effects could be abrogated by an AT1receptor antagonist losartan rather than an AT2receptor antagonist PD123319.
  
  
  CONCLUSIONS
  This study demonstrates that Ang II triggers mitochondrial-dependent apoptosis via facilitating mPTP opening through an AT1receptor-mediated fashion in dopaminergic neurons. These findings give insight into the effect of Ang II in the etiology of PD, and reinforce the application of AT1receptor antagonists for PD treatment.
authors.affiliation: Department of Neurology, Nanjing First Hospital, PR China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Ou
authors.affiliation: Department of Neurology, Nanjing First Hospital, PR China.
authors.forename: Teng
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Neurology, Nanjing First Hospital, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Department of Neurology, Nanjing First Hospital, PR China.
authors.forename: You-Yong
authors.initials: YY
authors.lastname: Tian
authors.affiliation: Department of Neurology, Nanjing First Hospital, PR China.
authors.forename: Jun-Shan
authors.initials: JS
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Nanjing First Hospital, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Neurology, Nanjing First Hospital, PR China.
authors.forename: Jian-Quan
authors.initials: JQ
authors.lastname: Shi
authors.affiliation: Department of Neurology, Nanjing First Hospital, PR China Zhangyingdong@aliyun.com.
authors.forename: Ying-Dong
authors.initials: YD
authors.lastname: Zhang
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D059290:Dopaminergic Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II
keywords: Parkinson’s disease; angiotensin II; apoptosis; cytochrome C; mitochondrial permeability transition pore; renin–angiotensin system