title: Neuroprotection by Orexin-A via HIF-1α induction in a cellular model of Parkinson's disease.
abstract: Orexin-A, a neuropeptide secreted by hypothalamic neurons, may be neuroprotective in many neurological conditions such as cerebral ischaemia. One mechanism postulated to be involved in the neuroprotection by Orexin-A is the induction of hypoxia inducible factor 1 alpha (HIF-1α). Parkinson's disease (PD) is a progressive neurodegenerative disorder and mitochondrial dysfunction has been demonstrated to play a role in its pathogenesis. Mitochondrial dysfunction may cause reduction of O2 consumption and subsequently activate prolyl hydroxylase, which leads to decreased level of HIF-1α. In this study, we used MPP(+)-treated SH-SY5Y cells as an in vitro cellular model of PD to test the role of Orexin-A as an inducer of HIF-1α. Our results showed that Orexin-A not only induced HIF-1α but also activated downstream targets of HIF-1α, such as vascular endothelial growth factor and erythropoietin. Thus, Orexin-A treatment attenuated MPP(+)-induced cell injury and this effect was blocked when HIF-1α was suppressed. Hence, we conclude that induction of HIF-1α is one of the mechanisms involved in the neuroprotection by Orexin-A.
authors.affiliation: Department of Neurology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, PR China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Shanghai Geriatric Institute of Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, PR China.
authors.forename: Te
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Experimental Therapeutics, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Xin-Qun
authors.initials: XQ
authors.lastname: Li
authors.affiliation: Department of Neurology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, PR China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, PR China.
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Zhu
authors.affiliation: Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Jankovic
authors.affiliation: Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: Tpan1@mdanderson.org.
authors.forename: Tian-Hong
authors.initials: TH
authors.lastname: Pan
authors.affiliation: Department of Neurology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, PR China. Electronic address: yunchw@medmail.com.cn.
authors.forename: Yun-Cheng
authors.initials: YC
authors.lastname: Wu
mesh_terms: D002460:Cell Line; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D020267:MPTP Poisoning / Q000139:chemically induced / Q000473:pathology*; D009479:Neuropeptides / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D000068797:Orexins; D013489:Suppression, Genetic / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C000596229:HCRT protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D018696:Neuroprotective Agents; D000068797:Orexins; D042461:Vascular Endothelial Growth Factor A
keywords: Dopaminergic neuron; HIF-1α; Neurodegenerative disease; Neuroprotection; Orexin-A; Parkinson's disease