Chronic alcohol ingestion exacerbates skeletal muscle myopathy in HIV-1 transgenic ratsReportar como inadecuado




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AIDS Research and Therapy

, 8:30

First Online: 16 August 2011Received: 16 March 2011Accepted: 16 August 2011

Abstract

BackgroundSeparately, chronic alcohol ingestion and HIV-1 infection are associated with severe skeletal muscle derangements, including atrophy and wasting, weakness, and fatigue. One prospective cohort study reported that 41% of HIV-infected patients met the criteria for alcoholism, however; few reports exist on the co-morbid effects of these two disease processes on skeletal muscle homeostasis. Thus, we analyzed the atrophic effects of chronic alcohol ingestion in HIV-1 transgenic rats and identified alterations to several catabolic and anabolic factors.

FindingsRelative plantaris mass, total protein content, and fiber cross-sectional area were reduced in each experimental group compared to healthy, control-fed rats. Alcohol abuse further reduced plantaris fiber area in HIV-1 transgenic rats. Consistent with previous reports, gene levels of myostatin and its receptor activin IIB were not increased in HIV-1 transgenic rat muscle. However, myostatin and activin IIB were induced in healthy and HIV-1 transgenic rats fed alcohol for 12 weeks. Catabolic signaling factors such as TGFβ1, TNFα, and phospho-p38-total-p38 were increased in all groups compared to controls. There was no effect on IL-6, leukemia inhibitory factor LIF, cardiotrophin-1 CT-1, or ciliary neurotrophic factor CNTF in control-fed, transgenic rats. However, the co-morbidity of chronic alcohol abuse and HIV-1-related protein expression decreased expression of the two anabolic factors, CT-1 and CNTF.

ConclusionsConsistent with previous reports, alcohol abuse accentuated skeletal muscle atrophy in an animal model of HIV-AIDS. While some catabolic pathways known to drive alcoholic or HIV-1-associated myopathies were also elevated in this co-morbid model e.g., TGFβ1, consistent expression patterns were not apparent. Thus, specific alterations to signaling mechanisms such as the induction of the myostatin-activin IIB system or reductions in growth factor signaling via CT-1- and CNTF-dependent mechanisms may play larger roles in the regulation of muscle mass in alcoholic, HIV-1 models.

List of abbreviationsCNTFciliary neurotrophic factor

CT-1cardiotrophin-1

CSAcross-sectional area

IGF-1insulin-like growth factor-1

IL-6interleukin-6

LIFleukemia inhibitory factor

MHCmyosin heavy chain

MuRFmuscle ring finger protein

NIAAANational Institutes of Alcohol Abuse and Alcoholism

SAIDSterminal stage acquired immune deficiency syndrome in SIV-infected Rhesus macaques

SIVsimian immunodeficiency virus

TGFβ1transforming growth factor β1

Electronic supplementary materialThe online version of this article doi:10.1186-1742-6405-8-30 contains supplementary material, which is available to authorized users.

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Autor: Caroline R Clary - Daniel M Guidot - Margaux A Bratina - Jeffrey S Otis

Fuente: https://link.springer.com/







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