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Metformin Targets Mitochondrial Electron Transport to Reduce Air-Pollution-Induced Thrombosis.
Soberanes, Saul; Misharin, Alexander V; Jairaman, Amit; Morales-Nebreda, Luisa; McQuattie-Pimentel, Alexandra C; Cho, Takugo; Hamanaka, Robert B; Meliton, Angelo Y; Reyfman, Paul A; Walter, James M; Chen, Ching-I; Chi, Monica; Chiu, Stephen; Gonzalez-Gonzalez, Francisco J; Antalek, Matthew; Abdala-Valencia, Hiam; Chiarella, Sergio E; Sun, Kaitlyn A; Woods, Parker S; Ghio, Andrew J; Jain, Manu; Perlman, Harris; Ridge, Karen M; Morimoto, Richard I; Sznajder, Jacob I; Balch, William E; Bhorade, Sangeeta M; Bharat, Ankit; Prakriya, Murali; Chandel, Navdeep S; Mutlu, Gökhan M; Budinger, G R Scott.
Afiliação
  • Soberanes S; Department of Medicine and Pulmonary and Critical Care Medicine, Northwestern University, 240 E Huron Street, M300, Chicago, IL 60611, USA.
  • Misharin AV; Department of Medicine and Pulmonary and Critical Care Medicine, Northwestern University, 240 E Huron Street, M300, Chicago, IL 60611, USA.
  • Jairaman A; Department of Pharmacology, Northwestern University, Chicago, IL 60611, USA.
  • Morales-Nebreda L; Department of Medicine and Pulmonary and Critical Care Medicine, Northwestern University, 240 E Huron Street, M300, Chicago, IL 60611, USA.
  • McQuattie-Pimentel AC; Department of Medicine and Pulmonary and Critical Care Medicine, Northwestern University, 240 E Huron Street, M300, Chicago, IL 60611, USA.
  • Cho T; Department of Medicine, University of Chicago, 5841 S Maryland Avenue, MC6026, Chicago, IL 60637, USA.
  • Hamanaka RB; Department of Medicine, University of Chicago, 5841 S Maryland Avenue, MC6026, Chicago, IL 60637, USA.
  • Meliton AY; Department of Medicine, University of Chicago, 5841 S Maryland Avenue, MC6026, Chicago, IL 60637, USA.
  • Reyfman PA; Department of Medicine and Pulmonary and Critical Care Medicine, Northwestern University, 240 E Huron Street, M300, Chicago, IL 60611, USA.
  • Walter JM; Department of Medicine and Pulmonary and Critical Care Medicine, Northwestern University, 240 E Huron Street, M300, Chicago, IL 60611, USA.
  • Chen CI; Department of Medicine and Pulmonary and Critical Care Medicine, Northwestern University, 240 E Huron Street, M300, Chicago, IL 60611, USA.
  • Chi M; Department of Medicine and Pulmonary and Critical Care Medicine, Northwestern University, 240 E Huron Street, M300, Chicago, IL 60611, USA.
  • Chiu S; Department of Surgery, Northwestern University, Chicago, IL 60611, USA.
  • Gonzalez-Gonzalez FJ; Department of Medicine and Pulmonary and Critical Care Medicine, Northwestern University, 240 E Huron Street, M300, Chicago, IL 60611, USA.
  • Antalek M; Rice Institute for Biomedical Research, Department of Molecular Biosciences, Northwestern University, Evanston, IL 60201, USA.
  • Abdala-Valencia H; Department of Medicine and Pulmonary and Critical Care Medicine, Northwestern University, 240 E Huron Street, M300, Chicago, IL 60611, USA.
  • Chiarella SE; Department of Medicine and Pulmonary and Critical Care Medicine, Northwestern University, 240 E Huron Street, M300, Chicago, IL 60611, USA.
  • Sun KA; Department of Medicine, University of Chicago, 5841 S Maryland Avenue, MC6026, Chicago, IL 60637, USA.
  • Woods PS; Department of Medicine, University of Chicago, 5841 S Maryland Avenue, MC6026, Chicago, IL 60637, USA.
  • Ghio AJ; United States Environmental Protections Agency, Chapel Hill, NC 27599, USA.
  • Jain M; Department of Medicine and Pulmonary and Critical Care Medicine, Northwestern University, 240 E Huron Street, M300, Chicago, IL 60611, USA.
  • Perlman H; Department of Medicine and Pulmonary and Critical Care Medicine, Northwestern University, 240 E Huron Street, M300, Chicago, IL 60611, USA.
  • Ridge KM; Department of Medicine and Pulmonary and Critical Care Medicine, Northwestern University, 240 E Huron Street, M300, Chicago, IL 60611, USA.
  • Morimoto RI; Rice Institute for Biomedical Research, Department of Molecular Biosciences, Northwestern University, Evanston, IL 60201, USA.
  • Sznajder JI; Department of Medicine and Pulmonary and Critical Care Medicine, Northwestern University, 240 E Huron Street, M300, Chicago, IL 60611, USA.
  • Balch WE; Scripps Research, Department of Molecular Medicine, La Jolla, CA 92037, USA.
  • Bhorade SM; Department of Medicine and Pulmonary and Critical Care Medicine, Northwestern University, 240 E Huron Street, M300, Chicago, IL 60611, USA.
  • Bharat A; Department of Surgery, Northwestern University, Chicago, IL 60611, USA.
  • Prakriya M; Department of Pharmacology, Northwestern University, Chicago, IL 60611, USA.
  • Chandel NS; Department of Medicine and Pulmonary and Critical Care Medicine, Northwestern University, 240 E Huron Street, M300, Chicago, IL 60611, USA.
  • Mutlu GM; Department of Medicine and Pulmonary and Critical Care Medicine, Northwestern University, 240 E Huron Street, M300, Chicago, IL 60611, USA; Department of Medicine, University of Chicago, 5841 S Maryland Avenue, MC6026, Chicago, IL 60637, USA. Electronic address: gmutlu@medicine.bsd.uchicago.edu.
  • Budinger GRS; Department of Medicine and Pulmonary and Critical Care Medicine, Northwestern University, 240 E Huron Street, M300, Chicago, IL 60611, USA. Electronic address: s-buding@northwestern.edu.
Cell Metab ; 29(2): 335-347.e5, 2019 02 05.
Article em En | MEDLINE | ID: mdl-30318339
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.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Trombose / Macrófagos Alveolares / Poluição do Ar / Material Particulado / Pneumopatias / Metformina / Mitocôndrias Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Revista: Cell Metab Assunto da revista: METABOLISMO Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Trombose / Macrófagos Alveolares / Poluição do Ar / Material Particulado / Pneumopatias / Metformina / Mitocôndrias Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Revista: Cell Metab Assunto da revista: METABOLISMO Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos