Institute of Preventive Medicine, School of Public Health, Dali University, No. 22, Wanhua Road, Dali, Yunnan 671000, People's Republic of China; Yunnan Center for Disease Control and Prevention, 1177 Xianghe Street, Chenggong District, Kunming, Yunnan 650500, People's Republic of China.
Institute of Preventive Medicine, School of Public Health, Dali University, No. 22, Wanhua Road, Dali, Yunnan 671000, People's Republic of China.
Ecotoxicol Environ Saf. 2024 Sep 1;282:116672. doi: 10.1016/j.ecoenv.2024.116672. Epub 2024 Jul 4.
Cadmium can lead to the death of pancreatic β cells, thus affecting the synthesis and secretion of insulin. However, the specific mechanisms underlying the cadmium-induced pancreatic β cell death have not been fully understood. In this study, roles of mA modification in regulating protein processing in endoplasmic reticulum (PPER) pathway in cadmium-induced pancreatic β cell death were explored. Our results demonstrated that cell viability and RNA mA modification level were decreased, while apoptosis rates increased after CdSO treatment in pancreatic β cells (NIT-1). In addition, expressions of Bcl-2, Xbp1, Col3a1, Bax, Chop, Dnajb1, and Hsp90aa1 were all significantly changed in CdSO treatment cells. The mA agonist entacapone (Ent) can prominently reverse the cytotoxicity effects of CdSO and alleviate the changes of protein expression induced by CdSO treatment. By contrast, mA inhibitor 3-Deazaadenosine (DAA) can synergistically enhance the cytotoxicity of CdSO and aggravate the disorder of protein levels caused by CdSO treatment. Interestingly, the results of the immunoprecipitation experiment indicate that Ythdc2, one of mA binding proteins, may regulate the PPER pathway molecules in an mA-dependent manner. In summary, our findings provide new directions for the prevention and treatment of the impairment of pancreatic β cell function induced by cadmium.
镉可导致胰岛β细胞死亡，从而影响胰岛素的合成和分泌。然而，镉诱导的胰岛β细胞死亡的具体机制尚不完全清楚。在本研究中，探讨了 mA 修饰在调控镉诱导的胰岛β细胞死亡中内质网（PPER）途径中蛋白质加工的作用。研究结果表明，CdSO 处理后胰岛β细胞（NIT-1）的细胞活力和 RNA mA 修饰水平降低，而细胞凋亡率增加。此外，CdSO 处理细胞中 Bcl-2、Xbp1、Col3a1、Bax、Chop、Dnajb1 和 Hsp90aa1 的表达均发生明显变化。mA 激动剂恩他卡朋（Ent）可显著逆转 CdSO 的细胞毒性作用，并减轻 CdSO 处理引起的蛋白表达变化。相比之下，mA 抑制剂 3-脱氮腺苷（DAA）可协同增强 CdSO 的细胞毒性，并加重 CdSO 处理引起的蛋白水平紊乱。有趣的是，免疫沉淀实验结果表明，mA 结合蛋白之一 Ythdc2 可能以 mA 依赖性方式调节 PPER 途径分子。综上所述，我们的研究结果为预防和治疗镉引起的胰岛β细胞功能损伤提供了新的方向。
