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Role of Hypoxia-Inducible Factors 1α (HIF1α) in SH-SY5Y Cell Autophagy Induced by Oxygen-Glucose Deprivation

BACKGROUND: HIF-1α plays an important role in hypoxia-ischemia brain damage. Accumulating evidences demonstrates that HIF-1α can contribute to cell autophagy. Oxygen-glucose deprivation (OGD) is a commonly used ischemic model in vitro. Our study was performed to investigate the influences of HIF-1α...

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Detalles Bibliográficos
Autores principales: Niu, Guohui, Zhu, Dengna, Zhang, Xiaoli, Wang, Jun, Zhao, Yunxia, Wang, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5954843/
https://www.ncbi.nlm.nih.gov/pubmed/29724989
http://dx.doi.org/10.12659/MSM.905140
Descripción
Sumario:BACKGROUND: HIF-1α plays an important role in hypoxia-ischemia brain damage. Accumulating evidences demonstrates that HIF-1α can contribute to cell autophagy. Oxygen-glucose deprivation (OGD) is a commonly used ischemic model in vitro. Our study was performed to investigate the influences of HIF-1α on autophagy in SH-SY5Y cells under OGD treatment. MATERIAL/METHODS: An OGD model was constructed in SH-SY5Y cells. PI method and MTT assay were used to test cell death and viability, respectively. Western blot assay was used to estimate the protein levels of HIF-1α and LC3. Quantitative GFP-LC3 light microscopy autophagy assay was performed for SH-SY5Y cells. 2ME2 and siRNA-HIF-1α were applied to investigate the effects of HIF-1α-knockdown on LC3 expression. Additionally, 3-MA (autophagy inhibitor) and autophagy inducer rapamycin (Rapa) were used to investigate the effects of autophagy on cell survival under OGD condition. RESULTS: Under OGD, the apoptosis of SH-SY5Ycells was increased while cell viability rate was decreased. The expression of HIF-1α was increased along with the advancement of OGD treatment and achieved the highest level at 24 h. However, inhibiting HIF-1α expression decreased the cell apoptosis and increased cell viability. LC3-II expression was gradually increased with the duration of OGD condition and knockdown of HIF-1α resulted in decreased expression of LC3. Inhibiting autophagy significantly enhanced the viability and reduced the apoptosis of SH-SY5Y cells, while enhancing autophagy showed the opposite effects. CONCLUSIONS: Enhanced expression of HIF-1α may be related to autophagy activation in SH-SY5Y cells, thus contributing to ischemic/hypoxic brain damage.