Procysteine stimulates expression of key anabolic factors and reduces plantaris atrophy in alcohol-fed rats.
BACKGROUND
Long-term alcohol ingestion may produce severe oxidant stress and lead to skeletal muscle dysfunction. Emerging evidence has suggested that members of the interleukin-6 (IL-6) family of cytokines play diverse roles in the regulation of skeletal muscle mass. Thus, our goals were (i) to minimize the degree of oxidant stress and attenuate atrophy by supplementing the diets of alcohol-fed rats with the glutathione precursor, procysteine, and (ii) to identify the roles of IL-6 family members in alcoholic myopathy.


METHODS
Age- and gender-matched Sprague-Dawley rats were fed the Lieber-DeCarli liquid diet containing either alcohol or an isocaloric substitution (control diet) for 35 weeks. Subgroups of alcohol-fed rats received procysteine (0.35%, w/v) for the final 12 weeks. Plantaris morphology was assessed by hematoxylin and eosin staining. Major components of glutathione metabolism were determined using assay kits. Real-time PCR was used to determine expression levels of several genes.


RESULTS
Plantaris muscles from alcohol-fed rats displayed extensive atrophy, as well as decreased glutathione levels, decreased activities of glutathione reductase and glutathione peroxidase, decreased superoxide dismutase (SOD)-2 (Mn-SOD2), and increased NADPH oxidase-1 gene expression-each indicative of significant oxidant stress. Alcohol also induced gene expression of catabolic factors including IL-6, oncostatin M, atrogin-1, muscle ring finger protein-1, and IGFBP-1. Procysteine treatment attenuated plantaris atrophy, restored glutathione levels, and increased catalase, Cu/Zn-SOD1, and Mn-SOD2 mRNA expression, but did not reduce other markers of oxidant stress or levels of these catabolic factors. Instead, procysteine stimulated gene expression of anabolic factors such as insulin-like growth factor-1, ciliary neurotrophic factor, and cardiotrophin-1.


CONCLUSIONS
Procysteine significantly attenuated, but did not completely abrogate, alcohol-induced oxidant stress or catabolic factors. Rather, procysteine minimized the extent of plantaris atrophy by inducing components of several anabolic pathways. Therefore, anti-oxidant treatments such as procysteine supplementation may benefit individuals with alcoholic myopathy.
Center for Emory University School of Medicine-Pulmonary, Allergy and Critical Care Medicine and Atlanta VA Medical Center, Decatur, Georgia 30002, USA. jsotis@emory.edu
Jeffrey S
JS
Otis
David M
DM
Guidot
D000428:Alcohol Drinking / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D009133:Muscular Atrophy / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011761:Pyrrolidonecarboxylic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D053778:Thiazolidines / Q000008:administration & dosage* / Q000494:pharmacology
D053778:Thiazolidines; D000431:Ethanol; D011761:Pyrrolidonecarboxylic Acid; C029536:2-oxothiazolidine-4-carboxylic acid