Roles of mA modification in regulating PPER pathway in cadmium-induced pancreatic β cell death.

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.