Protective effect of hydralazine on a cellular model of Parkinson’s disease: a possible role of hypoxia-inducible factor (HIF)-1α

• Published in: Biochemistry and cell biology Vol. 98; no. 3; pp. 405 - 414
• Main Authors: Mehrabani, Mehrnaz, Nematollahi, Mohammad Hadi, Tarzi, Mojde Esmaeili, Juybari, Kobra Bahrampour, Abolhassani, Moslem, Sharifi, Ali Mohammad, Paseban, Hamze, Saravani, Mohsen, Mirzamohammadi, Solmaz
• Format: Journal Article
• Language: English
• Published: 1840 Woodward Drive, Suite 1, Ottawa, ON K2C 0P7 NRC Research Press 01.06.2020; Canadian Science Publishing NRC Research Press
• Subjects: 6-Hydroxydopamine; Antihypertensives; Antioxidants; Antioxidants - metabolism; Apoptosis; Cell Hypoxia; Cell Line, Tumor; Cell Survival; cellules SH-SY5Y; Cytotoxicity; Dopamine; Dopamine - metabolism; Dopamine transporter; Exposure; Genes; Growth factors; HIF-1α; Humans; hydralazine; Hydralazine - pharmacology; Hydroxylase; Hypoxia; Hypoxia-inducible factor 1; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Hypoxia-inducible factors; Levels; maladie de Parkinson; Malondialdehyde; Malondialdehyde - metabolism; Movement disorders; Neurodegenerative diseases; Nitric oxide; Nitric Oxide - metabolism; Oxidopamine - pharmacology; Parkinson Disease - drug therapy; Parkinson Disease - metabolism; Parkinson's disease; Priming; Proteins; SH-SY5Y cells; Signal transduction; Signaling; Superoxide dismutase; Superoxide Dismutase - metabolism; Toxicity; Transcription; Tyrosine; Tyrosine 3-monooxygenase; Vascular endothelial growth factor; Western blotting; 6-hydroxydopamine; cellules SH-SY5Y; hydralazine; SH-SY5Y cells; maladie de Parkinson; HIF-1α; Parkinson’s disease
• ISSN: 0829-8211; 1208-6002
• DOI: 10.1139/bcb-2019-0117

Parkinson’s disease (PD) is a neurodegenerative disease accompanied by a low expression level of cerebral hypoxia-inducible factor (HIF-1α). Hence, activating the hypoxia-signaling pathway may be a favorable therapeutic approach for curing PD. This study explored the efficacy of hydralazine, a well-known antihypertensive agent, for restoring the impaired HIF-1 signaling in PD, with the aid of 6-hydroxydopamine (6-OHDA)-exposed SH-SY5Y cells. The cytotoxicity of hydralazine and 6-OHDA on the SH-SY5Y cells were evaluated by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and apoptosis detection assays. The activities of malondialdehyde, nitric oxide (NO), ferric reducing antioxidant power (FRAP), and superoxide dismutase (SOD) were also measured. Expression levels of HIF-1α and its downstream genes at the protein level were assessed by Western blotting. Hydralazine showed no toxic effects on SH-SY5Y cells, at the concentration of ≤50 μmol/L. Hydralazine decreased the levels of apoptosis, malondialdehyde, and NO, and increased the activities of FRAP and SOD in cells exposed to 6-OHDA. Furthermore, hydralazine up-regulated the protein expression levels of HIF-1α, vascular endothelial growth factor, tyrosine hydroxylase, and dopamine transporter in the cells also exposed to 6-OHDA, by comparison with the cells exposed to 6-OHDA alone. In summary, hydralazine priming could attenuate the deleterious effects of 6-OHDA on SH-SY5Y cells by increasing cellular antioxidant capacity, as well as the protein levels of HIF-1α and its downstream target genes.