Neuroprotection by Orexin-A via HIF-1α induction in a cellular model of Parkinson's disease
| Autor: | Joseph Jankovic, Tian Hong Pan, Te Liu, Yun Cheng Wu, Ye Liu, Ya Feng, Xin Qun Li, Xiao Ying Zhu |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Vascular Endothelial Growth Factor A
medicine.medical_specialty Parkinson's disease Pharmacology Neuroprotection Cell Line Pathogenesis Hypoxia-Inducible Factor 1-Alpha Orexin-A chemistry.chemical_compound Suppression Genetic Internal medicine Humans Medicine Orexins business.industry General Neuroscience Neuropeptides Intracellular Signaling Peptides and Proteins MPTP Poisoning Hypoxia-Inducible Factor 1 alpha Subunit medicine.disease Vascular endothelial growth factor Neuroprotective Agents Endocrinology nervous system chemistry TBST Cellular model business |
| Zdroj: | Neuroscience Letters. 579:35-40 |
| ISSN: | 0304-3940 |
| DOI: | 10.1016/j.neulet.2014.07.014 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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