Cytoprotective Effects of N-Acetylcysteine on Streptozotocin- Induced Oxidative Stress and Apoptosis in RIN-5F Pancreatic β-Cells
Cytoprotective Effects of N-Acetylcysteine on Streptozotocin- Induced Oxidative Stress and Apoptosis in RIN-5F Pancreatic β-Cells
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DOI：
10.1159/000495200
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Raza, Haider
中科院分区：
文献类型：
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作者：
Al-Nahdi, Arwa M. T.;John, Annie;Raza, Haider
背景/目标：许多研究报道了在糖尿病及其并发症的发展中活性氧（ROS）的过度产生和线粒体能量代谢的改变。N-乙酰半胱氨酸（NAC）在糖尿病中的潜在保护作用已在许多治疗研究中报道。NAC已被证明可以减少氧化应激并增强组织中的氧化还原电位，保护它们免受糖尿病中氧化应激相关并发症的影响。在本研究中，我们旨在研究NAC对STZ诱导的胰岛素分泌Rin-5 F胰腺细胞毒性的保护作用的分子机制。方法：将Rin-5 F细胞培养至80%汇合，然后在10 mMNAC存在或不存在下用10 mMSTZ处理24 h。采用分光光度法、流式细胞仪和Western印迹技术对亚细胞分离后的氧化应激、GSH依赖性代谢和线粒体呼吸功能进行了研究。结果如下：我们的研究结果表明，STZ诱导的氧化应激和细胞凋亡引起胰岛素分泌抑制，而NAC治疗恢复氧化还原稳态，提高胰岛素分泌在控制细胞和防止STZ处理的细胞凋亡。此外，NAC通过部分恢复线粒体酶和恢复膜电位来减弱STZ诱导的线粒体功能抑制。STZ诱导的DNA损伤和凋亡蛋白的表达显着抑制NAC处理的细胞。结论：我们的研究结果表明，NAC的细胞保护作用是通过抑制氧化应激和细胞凋亡和恢复GSH稳态和线粒体生物能量介导的。因此，这项研究可能有助于更好地了解胰腺细胞对STZ诱导的细胞毒性的细胞防御机制。
Background/Aims: Numerous studies have reported overproduction of reactive oxygen species (ROS) and alterations in mitochondrial energy metabolism in the development of diabetes and its complications. The potential protective effects of N-acetylcysteine (NAC) in diabetes have been reported in many therapeutic studies. NAC has been shown to reduce oxidative stress and enhance redox potential in tissues protecting them against oxidative stress associated complications in diabetes. In the current study, we aimed to investigate the molecular mechanisms of the protective action of NAC on STZ-induced toxicity in insulin secreting Rin-5F pancreatic -cells. Methods: Rin-5F cells were grown to 80% confluence and then treated with 10mM STZ for 24h in the presence or absence of 10mM NAC. After sub-cellular fractionation, oxidative stress, GSH-dependent metabolism and mitochondrial respiratory functions were studied using spectrophotometric, flow cytometric and Western blotting techniques. Results: Our results showed that STZ-induced oxidative stress and apoptosis caused inhibition in insulin secretion while NAC treatment restored the redox homeostasis, enhanced insulin secretion in control cells and prevented apoptosis in STZ-treated cells. Moreover, NAC attenuated the inhibition of mitochondrial functions induced by STZ through partial recovery of the mitochondrial enzymes and restoration of membrane potential. STZ-induced DNA damage and expression of apoptotic proteins were significantly inhibited in NAC-treated cells. Conclusion: Our results suggest that the cytoprotective action of NAC is mediated via suppression of oxidative stress and apoptosis and restoration of GSH homeostasis and mitochondrial bioenergetics. This study may, thus, help in better understanding the cellular defense mechanisms of pancreatic -cells against STZ-induced cytotoxicity.