| Literature DB >> 30318339 |
Saul Soberanes1, Alexander V Misharin1, Amit Jairaman2, Luisa Morales-Nebreda1, Alexandra C McQuattie-Pimentel1, Takugo Cho3, Robert B Hamanaka3, Angelo Y Meliton3, Paul A Reyfman1, James M Walter1, Ching-I Chen1, Monica Chi1, Stephen Chiu4, Francisco J Gonzalez-Gonzalez1, Matthew Antalek5, Hiam Abdala-Valencia1, Sergio E Chiarella1, Kaitlyn A Sun3, Parker S Woods3, Andrew J Ghio6, Manu Jain1, Harris Perlman1, Karen M Ridge1, Richard I Morimoto5, Jacob I Sznajder1, William E Balch7, Sangeeta M Bhorade1, Ankit Bharat4, Murali Prakriya2, Navdeep S Chandel1, Gökhan M Mutlu8, G R Scott Budinger9.
Abstract
Urban particulate matter air pollution induces the release of pro-inflammatory cytokines including interleukin-6 (IL-6) from alveolar macrophages, resulting in an increase in thrombosis. Here, we report that metformin provides protection in this murine model. Treatment of mice with metformin or exposure of murine or human alveolar macrophages to metformin prevented the particulate matter-induced generation of complex III mitochondrial reactive oxygen species, which were necessary for the opening of calcium release-activated channels (CRAC) and release of IL-6. Targeted genetic deletion of electron transport or CRAC channels in alveolar macrophages in mice prevented particulate matter-induced acceleration of arterial thrombosis. These findings suggest metformin as a potential therapy to prevent some of the premature deaths attributable to air pollution exposure worldwide.Entities:
Keywords: air pollution; calcium channels; electron transport chain; mitochondria; proteostasis; reactive oxygen species; signaling; thrombosis
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Year: 2018 PMID： 30318339 PMCID： PMC6365216 DOI： 10.1016/j.cmet.2018.09.019
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287