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IFN-γ and androgens disrupt mitochondrial function in murine myocytes.
Fenimore, John M; Springer, Danielle A; Romero, Maria E; Edmondson, Elijah F; McVicar, Dan W; Yanpallewar, Sudhirkumar; Sanford, Michael; Spindel, Thea; Engle, Elizabeth; Meyer, Thomas J; Valencia, Julio C; Young, Howard A.
Afiliación
  • Fenimore JM; Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
  • Springer DA; Murine Phenotyping Core, National Heart, Lung, and Blood Institute, Bethesda, MD, USA.
  • Romero ME; CVPath Institute, Gaithersburg, MD, USA.
  • Edmondson EF; Pathology and Histology Lab, National Cancer Institute, Frederick, MD, USA.
  • McVicar DW; Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
  • Yanpallewar S; Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
  • Sanford M; Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
  • Spindel T; Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
  • Engle E; Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
  • Meyer TJ; CCR Collaborative Bioinformatics Resource (CCBR), Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
  • Valencia JC; Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
  • Young HA; Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
J Pathol ; 260(3): 276-288, 2023 07.
Article en En | MEDLINE | ID: mdl-37185821
The effect of cytokines on non-traditional immunological targets under conditions of chronic inflammation is an ongoing subject of study. Fatigue is a symptom often associated with autoimmune diseases. Chronic inflammatory response and activated cell-mediated immunity are associated with cardiovascular myopathies which can be driven by muscle weakness and fatigue. Thus, we hypothesize that immune dysfunction-driven changes in myocyte mitochondria may play a critical role in fatigue-related pathogenesis. We show that persistent low-level expression of IFN-γ in designated IFN-γ AU-Rich Element deletion mice (ARE mice) under androgen exposure resulted in mitochondrial and metabolic deficiencies in myocytes from male or castrated ARE mice. Most notably, echocardiography unveiled that low ejection fraction in the left ventricle post-stress correlated with mitochondrial deficiencies, explaining how heart function decreases under stress. We report that inefficiencies and structural changes in mitochondria, with changes to expression of mitochondrial genes, are linked to male-biased fatigue and acute cardiomyopathy under stress. Our work highlights how male androgen hormone backgrounds and active autoimmunity reduce mitochondrial function and the ability to cope with stress and how pharmacological blockade of stress signal protects heart function. These studies provide new insight into the diverse actions of IFN-γ in fatigue, energy metabolism, and autoimmunity. © 2023 The Pathological Society of Great Britain and Ireland. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interferón gamma / Andrógenos Límite: Animals Idioma: En Revista: J Pathol Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interferón gamma / Andrógenos Límite: Animals Idioma: En Revista: J Pathol Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido