Cancer-induced Cardiac Atrophy Adversely Affects Myocardial Redox State and Mitochondrial Oxidative Characteristics.

Autor: Lee DE; Cachexia Research Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, Arkansas, USA.; Laboratory for Functional Optical Imaging and Spectroscopy, Department of Biomedical Engineering, University of Arkansas, Fayetteville, Arkansas, USA., Brown JL; Cachexia Research Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, Arkansas, USA., Rosa-Caldwell ME; Cachexia Research Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, Arkansas, USA., Perry RA; Exercise Muscle Biology Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, Arkansas, USA., Brown LA; Exercise Muscle Biology Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, Arkansas, USA., Haynie WS; Exercise Muscle Biology Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, Arkansas, USA., Washington TA; Exercise Muscle Biology Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, Arkansas, USA., Wiggs MP; Department of Health and Kinesiology, University of Texas at Tyler, Tyler, Texas, USA., Rajaram N; Laboratory for Functional Optical Imaging and Spectroscopy, Department of Biomedical Engineering, University of Arkansas, Fayetteville, Arkansas, USA., Greene NP; Cachexia Research Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, Arkansas, USA.
Jazyk: angličtina
Zdroj: JCSM rapid communications [JCSM Rapid Commun] 2021 Jan-Jun; Vol. 4 (1), pp. 3-15. Date of Electronic Publication: 2020 Aug 07.
DOI: 10.1002/rco2.18
Abstrakt: Cachexia presents in 80% of advanced cancer patients; however, cardiac atrophy in cachectic patients receives little attention. This cardiomyopathy contributes to increased occurrence of adverse cardiac events compared to age-matched population norms. Research on cardiac atrophy has focused on remodeling; however, alterations in metabolic properties may be a primary contributor.
Purpose: Determine how cancer-induced cardiac atrophy alters mitochondrial turnover, mitochondrial mRNA translation machinery and in-vitro oxidative characteristics.
Methods: Lewis lung carcinoma (LLC) tumors were implanted in C57BL6/J mice and grown for 28days to induce cardiac atrophy. Endogenous metabolic species, and markers of mitochondrial function were assessed. H9c2 cardiomyocytes were cultured in LLC-conditioned media with(out) the antioxidant MitoTempo. Cells were analyzed for ROS, oxidative capacity, and hypoxic resistance.
Results: LLC heart weights were ~10% lower than controls. LLC hearts demonstrated ~15% lower optical redox ratio (FAD/FAD+NADH) compared to PBS controls. When compared to PBS, LLC hearts showed ~50% greater COX-IV and VDAC, attributed to ~50% lower mitophagy markers. mt-mRNA translation machinery was elevated similarly to markers of mitochondrial content. mitochondrial DNA-encoded Cytb was ~30% lower in LLC hearts. ROS scavengers GPx-3 and GPx-7 were ~50% lower in LLC hearts. Treatment of cardiomyocytes with LLC-conditioned media resulted in higher ROS (25%), lower oxygen consumption rates (10% at basal, 75% at maximal), and greater susceptibility to hypoxia (~25%) -- which was reversed by MitoTempo.
Conclusion: These results substantiate metabolic cardiotoxic effects attributable to tumor-associated factors and provide insight into interactions between mitochondrial mRNA translation, ROS mitigation, oxidative capacity and hypoxia resistance.
Competing Interests: Conflicts of Interest: The authors declare no conflicts of interest associated with this publication.
Databáze: MEDLINE
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