Xiang Ruo Lan, Mei Mei, Su Yun Chao, Li Li, Wang Jin Yu, Wu Li Ling
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing 100191, China.
Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, China.
Biomed Environ Sci. 2015 Mar;28(3):169-77. doi: 10.3967/bes2015.023.
Interferon-γ (IFN-γ) plays an important role in apoptosis and was shown to increase the risk of diabetes. Visfatin, an adipokine, has anti-diabetic, anti-tumor, and regulating inflammatory properties. In this study we investigated the effect of visfatin on IFN-γ-induced apoptosis in rat pancreatic β-cells.
The RINm5F (rat insulinoma cell line) cells exposed to IFN-γ were treated with or without visfatin. The viability and apoptosis of the cells were assessed by using MTT and flow cytometry. The expressions of mRNA and protein were detected by using real-time PCR and western blot analysis.
The exposure of RINm5F cells to IFN-γ for 48 h led to increased apoptosis percentage of the cells. Visfatin pretreatment significantly increased the cell viability and reduced the cell apoptosis induced by IFN-γ. IFN-γ-induced increase in expression of p53 mRNA and cytochrome c protein, decrease in mRNA and protein levels of anti-apoptotic protein Bcl-2 were attenuated by visfatin pretreatment. Visfatin also increased AMPK and ERK1/2 phosphorylation and the anti-apoptotic action of visfatin was attenuated by the AMPK and ERK1/2 inhibitor.
These results suggested that visfatin protected pancreatic islet cells against IFN-γ-induced apoptosis via mitochondria-dependent apoptotic pathway. The anti-apoptotic action of visfatin is mediated by activation of AMPK and ERK1/2 signaling molecules.
干扰素-γ（IFN-γ）在细胞凋亡中起重要作用，且已表明其会增加患糖尿病的风险。内脂素是一种脂肪因子，具有抗糖尿病、抗肿瘤及调节炎症的特性。在本研究中，我们调查了内脂素对IFN-γ诱导的大鼠胰腺β细胞凋亡的影响。
将暴露于IFN-γ的RINm5F（大鼠胰岛素瘤细胞系）细胞用或不用内脂素进行处理。通过MTT法和流式细胞术评估细胞的活力和凋亡情况。采用实时PCR和蛋白质印迹分析检测mRNA和蛋白质的表达。
RINm5F细胞暴露于IFN-γ 48小时导致细胞凋亡百分比增加。内脂素预处理显著提高了细胞活力，并减少了IFN-γ诱导的细胞凋亡。内脂素预处理减弱了IFN-γ诱导的p53 mRNA表达增加和细胞色素c蛋白表达增加，以及抗凋亡蛋白Bcl-2 mRNA和蛋白质水平的降低。内脂素还增加了AMPK和ERK1/2的磷酸化，且内脂素的抗凋亡作用被AMPK和ERK1/2抑制剂减弱。
这些结果表明，内脂素通过线粒体依赖性凋亡途径保护胰岛细胞免受IFN-γ诱导的凋亡。内脂素的抗凋亡作用是由AMPK和ERK1/2信号分子的激活介导的。
