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Nova1 mediates resistance of rat pheochromocytoma cells to hypoxia-induced apoptosis via the Bax/Bcl-2/caspase-3 pathway.

ABSTRACT: Neuro-oncological ventral antigen 1 (Nova1) is a well known brain-specific splicing factor. Several studies have identified Nova1 as a regulatory protein at the top of a hierarchical network. However, the function of Nova1 during hypoxia remains poorly understood. This study aimed to investigate the protective effect of Nova1 against cell hypoxia and to further explore the Bax/Bcl-2/caspase-3 pathway as a potential mechanism. During hypoxia, the survival rate of pheochromocytoma PC12 cells was gradually decreased and the apoptosis rate was gradually increased, peaking at 48 h of hypoxia. At 48 h after transfection of PC12 cells with pCMV-Myc-Nova1, the expression of Nova1 was significantly increased, with wide distribution in the cytoplasm and nucleus. Moreover, the survival rate was significantly increased and the apoptosis rate was significantly decreased. Additionally, the mRNA and protein expression levels of Bax and caspase-3 were significantly increased in the pCMV-Myc group and significantly decreased in the pCMV?Myc-Nova1 group, whereas that of Bcl-2 was significantly decreased in the pCMV-Myc group and significantly increased in the pCMV-Myc-Nova1 group. This study indicated that Nova1 could be linked to resistance to the hypoxia-induced apoptosis of PC12 cells via the Bax/Bcl-2/caspase-3 pathway, and this finding may be of significance for exploring novel mechanisms of hypoxia and the treatment of hypoxia-associated diseases.

SUBMITTER: Li H

PROVIDER: S-EPMC5593465 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Nova1 mediates resistance of rat pheochromocytoma cells to hypoxia-induced apoptosis via the Bax/Bcl-2/caspase-3 pathway.

Li Hualing H Lv Bei B Kong Ling L Xia Jing J Zhu Ming M Hu Lijuan L Zhen Danyang D Wu Yifan Y Jia Xiaoqin X Zhu Sujuan S Cui Hengmi H

International journal of molecular medicine 20170803 4

Neuro-oncological ventral antigen 1 (Nova1) is a well known brain-specific splicing factor. Several studies have identified Nova1 as a regulatory protein at the top of a hierarchical network. However, the function of Nova1 during hypoxia remains poorly understood. This study aimed to investigate the protective effect of Nova1 against cell hypoxia and to further explore the Bax/Bcl-2/caspase-3 pathway as a potential mechanism. During hypoxia, the survival rate of pheochromocytoma PC12 cells was g ...[more]

PMID: 28791345

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Project description:BackgroundApoptosis plays a critical role in controlling the proliferation and differentiation of germ cells during spermatogenesis. Dysregulation of the fine-tuned balance may lead to the onset of testicular diseases. In this study, we investigated the activation status of apoptosis pathways in the testicular tissues under the background of an asthmatic mouse model.MethodsTen BALB/c mice were divided into two groups: the acute asthma group and the control group. In the acute asthma group, ovalbumin (OVA)-sensitized mice were challenged with aerosolized OVA for 7 days, while the control group was treated with physiological saline. After that, both epididymis and testis were collected to determine the sperm count and motility. Apoptosis in the testis was evaluated by DNA ladder, immunochemistry and further by PCR array of apoptosis-related genes. Finally, the cleavage of caspase-3 and poly ADP-ribose polymerase (PARP) was determined by western blot and the enzymatic activities of caspase-9 and 3/7 were assessed using Caspase-Glo kits.ResultsCompared with control mice, significant decreases in the body weight, testis weight, sperm count and motility were seen in the experimental group. DNA ladder and immunochemistry showed significant increase in apoptotic index of the asthmatic testis, whereas a decrease in mRNA expression of Bcl-2 and increases in Bax, BNIP3, caspase-9, and AIF were observed in the asthma group. Furthermore, protein levels of AIF were significantly upregulated, while the translational expression of Bcl-2 was downregulated markedly. Consistently, caspase-9 activity in the testis of asthma mice was significantly higher than that of the control group.ConclusionCollectively, these results showed that Bcl-2-caspase-9 apoptosis pathway was clearly activated in the testis of asthmatic mice with the increased expression of apoptosis-related genes and proteins. To our knowledge, this is the first report demonstrating that asthma could lead to the activation of the mitochondrial apoptosis signaling pathway in the mouse testis.

Dataset Information

Nova1 mediates resistance of rat pheochromocytoma cells to hypoxia-induced apoptosis via the Bax/Bcl-2/caspase-3 pathway.

Publications

Nova1 mediates resistance of rat pheochromocytoma cells to hypoxia-induced apoptosis via the Bax/Bcl-2/caspase-3 pathway.

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