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m 6 A methylation-mediated PGC-1α contributes to ferroptosis via regulating GSTK1 in arsenic-induced hepatic insulin resistance.
- Source :
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The Science of the total environment [Sci Total Environ] 2023 Dec 20; Vol. 905, pp. 167202. Date of Electronic Publication: 2023 Sep 18. - Publication Year :
- 2023
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Abstract
- Arsenic exposure has been closely linked to hepatic insulin resistance (IR) and ferroptosis with the mechanism elusive. Peroxisome proliferator γ-activated receptor coactivator 1-α (PGC-1α) is essential for glucose metabolism as well as for the production of reactive oxygen species (ROS). However, it was unclear whether there is a regulatory connection between PGC-1α and ferroptosis. Besides, the definitive mechanism of arsenic-induced hepatic IR progression remains to be determined. Here, we found that hepatic insulin sensitivity impaired by sodium arsenite (NaAsO <subscript>2</subscript> ) could be reversed by inhibiting ferroptosis. Mechanistically, we found that PGC-1α suppression inhibited the protein expression of glutathione s-transferase kappa 1 (GSTK1) via nuclear respiratory factor 1 (NRF1), thereby increasing ROS accumulation and promoting ferroptosis. Furthermore, we showed that NaAsO <subscript>2</subscript> induced hepatic IR and ferroptosis via methyltransferase-like 14 (METTL14) and YTH domain-containing family protein 2 (YTHDF2)-mediated N6-methyladenosine (m <superscript>6</superscript> A) of PGC-1α mRNA. In conclusion, NaAsO <subscript>2</subscript> -mediated PGC-1α suppression was m <superscript>6</superscript> A methylation-dependent and induced ferroptosis via the PGC-1α/NRF1/GSTK1 pathway in hepatic IR. The data might provide insight into potential targets for diabetes prevention and treatment.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1879-1026
- Volume :
- 905
- Database :
- MEDLINE
- Journal :
- The Science of the total environment
- Publication Type :
- Academic Journal
- Accession number :
- 37730054
- Full Text :
- https://doi.org/10.1016/j.scitotenv.2023.167202