Ambrosio 2014 Free Radic Biol Med
|Ambrosio F, Brown E, Stolz D, Ferrari R, Goodpaster BH, Deasy B, Distefano G, Roperti A, Cheikhi A, Garciafigueroa Y, Barchowsky A (2014) Arsenic induces sustained impairment of skeletal muscle and muscle progenitor cell ultrastructure and bioenergetics. Free Radic Biol Med 74C:64-73.|
Abstract: Over 4 million individuals in the United States, and over 140 million individuals worldwide, are exposed daily to arsenic-contaminated drinking water. Human exposures can range from below the current limit of 10μg/L to over 1mg/L, with 100μg/L promoting disease in a large portion of those exposed. Although increased attention has recently been paid to myopathy following arsenic exposure, the pathogenic mechanisms underlying clinical symptoms remain poorly understood. This study tested the hypothesis that arsenic induces lasting muscle mitochondrial dysfunction and impairs metabolism. Compared to nonexposed controls, mice exposed to drinking water containing 100μg/L arsenite for 5 weeks demonstrated impaired muscle function, mitochondrial myopathy, and altered oxygen consumption that were concomitant with increased mitochondrial fusion gene transcription. There were no differences in the levels of inorganic arsenic or its monomethyl and dimethyl metabolites between controls and exposed muscles, confirming that arsenic does not accumulate in muscle. Nevertheless, muscle progenitor cells isolated from exposed mice recapitulated the aberrant myofiber phenotype and were more resistant to oxidative stress, generated more reactive oxygen species, and displayed autophagic mitochondrial morphology, compared to cells isolated from nonexposed mice. These pathological changes from a possible maladaptive oxidative stress response provide insight into declines in muscle functioning caused by exposure to this common environmental contaminant.
• Keywords: Metabolism, Mitochondria, Resistance to stress, Free radicals
• O2k-Network Lab: US FL Orlando Goodpaster BH
Labels: MiParea: Respiration, Pharmacology;toxicology
Organism: Mouse Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue
Coupling state: LEAK, OXPHOS, ET Pathway: F, N, NS HRR: Oxygraph-2k