Roles of m 6 A 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 m ⁶ A 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 m ⁶ A modification level were decreased, while apoptosis rates increased after CdSO ₄ 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 ₄ treatment cells. The m ⁶ A agonist entacapone (Ent) can prominently reverse the cytotoxicity effects of CdSO ₄ and alleviate the changes of protein expression induced by CdSO ₄ treatment. By contrast, m ⁶ A inhibitor 3-Deazaadenosine (DAA) can synergistically enhance the cytotoxicity of CdSO ₄ and aggravate the disorder of protein levels caused by CdSO ₄ treatment. Interestingly, the results of the immunoprecipitation experiment indicate that Ythdc2, one of m ⁶ A binding proteins, may regulate the PPER pathway molecules in an m ⁶ A-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.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Zuoshun HE reports was provided by grants from the National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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