Upregulation of HIF-1α protects neuroblastoma cells from hypoxia-induced apoptosis in a RhoA-dependent manner

被引:12
作者
Yin, Cui-Ping [1 ]
Guan, Shang-Hui [2 ]
Zhang, Bo [3 ]
Wang, Xue-Xin [4 ]
Yue, Shou-Wei [1 ]
机构
[1] Shandong Univ, Qilu Hosp, Dept Phys Med & Rehabil, Jinan 250012, Shandong, Peoples R China
[2] Shandong Univ, Qilu Hosp, Dept Radiat Oncol, Jinan 250012, Shandong, Peoples R China
[3] Dongying Peoples Hosp, Dept Phys Med & Rehabil, Dongying 257091, Shandong, Peoples R China
[4] Yuhuangding Hosp, Dept Phys Med & Rehabil, Yantai 264000, Shandong, Peoples R China
关键词
hypoxia-inducible factor alpha; hypoxia; apoptosis; PC12; cells; Ras homolog; member A; FOCAL CEREBRAL-ISCHEMIA; SMOOTH-MUSCLE-CELLS; INDUCIBLE FACTOR-I; HMG-COA REDUCTASE; CANCER CELLS; TRANSCRIPTION FACTORS; BCL-2; EXPRESSION; EPITHELIAL-CELLS; GENE-EXPRESSION; GTPASES;
D O I
10.3892/mmr.2015.4267
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Hypoxic conditions regulate several metabolic enzymes and transcription factors that are involved in cancer, ischemia and pulmonary diseases. The Ras homolog (Rho) family, including Rho member A (RhoA), is involved in reorganization of the actin cytoskeleton, cell migration and in the regulation of apoptosis and gene transcription. The aim of the present study was to investigate the expression of hypoxia-inducible factor (HIF)-alpha and the activity of RhoA in PC12 neuroblastoma cells under hypoxic conditions. The upregulation of HIF-alpha and RhoA by hypoxia was determined using reverse transcription-quantitative polymerase chain reaction and western blot assays, cell apoptosis was analyzed using flow cytometry, and the activity of caspase 3 was examined using a western blot assay and caspase 3 activity assay kit. The PC12 cells were induced to apoptosis following exposure to hypoxia, and exhibited increased expression of HIP-alpha and increased mRNA and protein expression levels of RhoA. The overexpression of HIP-alpha attenuated the hypoxia-induced apoptosis of the PC12 cells. In addition, RhoA knockdown using small interfering RNA abrogated the antagonism of HIF-1 alpha towards hypoxia-induced apoptosis. The results of the present study confirmed the protective role of HIP-1 alpha and RhoA in hypoxia-induced PC12 cell apoptosis, and that the upregulation of HIF-1 alpha by hypoxia is RhoA-dependent.
引用
收藏
页码:7123 / 7131
页数:9
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