Top

AIDS Research and Therapy

Published in:

Open Access 01-12-2011 | Research

Chronic alcohol ingestion exacerbates skeletal muscle myopathy in HIV-1 transgenic rats

Authors: Caroline R Clary, Daniel M Guidot, Margaux A Bratina, Jeffrey S Otis

Published in: AIDS Research and Therapy | Issue 1/2011

Abstract

Background

Separately, 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.

Findings

Relative 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.

Conclusions

Consistent 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.

Available only for authorised users

Kresina TF, Flexner CW, Sinclair J, Correia MA, Stapleton JT, Adeniyi-Jones S, Cargill V, Cheever LW: Alcohol use and HIV pharmacotherapy. AIDS Res Hum Retroviruses. 2002, 18 (11): 757-770. 10.1089/08892220260139495CrossRefPubMed

Moss M, Burnham EL: Chronic alcohol abuse, acute respiratory distress syndrome, and multiple organ dysfunction. Crit Care Med. 2003, 31 (4 Suppl): S207-212.CrossRefPubMed

Reid W, Sadowska M, Denaro F, Rao S, Foulke J, Hayes N, Jones O, Doodnauth D, Davis H, Sill A: An HIV-1 transgenic rat that develops HIV-related pathology and immunologic dysfunction. Proc Natl Acad Sci USA. 2001, 98 (16): 9271-9276. 10.1073/pnas.161290298PubMedCentralCrossRefPubMed

Franchi S, Sacerdote P, Moretti S, Gerra G, Leccese V, Tallone MV, Panerai AE, Somaini L: The effects of alcoholism pharmacotherapy on immune responses in alcohol-dependent patients. Int J Immunopathol Pharmacol. 23 (3): 847-855.

Naicker S, Fabian J: Risk factors for the development of chronic kidney disease with HIV/AIDS. Clin Nephrol. 74 (Suppl 1): S51-56.

Alcohol Alert.http://pubs.niaaa.nih.gov/publications/aa57.htm

Petry NM: Alcohol use in HIV patients: what we don't know may hurt us. Int J STD AIDS. 1999, 10 (9): 561-570. 10.1258/0956462991914654CrossRefPubMed

Fama R, Rosenbloom MJ, Nichols BN, Pfefferbaum A, Sullivan EV: Working and episodic memory in HIV infection, alcoholism, and their comorbidity: baseline and 1-year follow-up examinations. Alcohol Clin Exp Res. 2009, 33 (10): 1815-1824. 10.1111/j.1530-0277.2009.01020.xPubMedCentralCrossRefPubMed

Meyerhoff DJ: Effects of alcohol and HIV infection on the central nervous system. Alcohol Res Health. 2001, 25 (4): 288-298.PubMed

10.

Molina PE, Lang CH, McNurlan M, Bagby GJ, Nelson S: Chronic alcohol accentuates simian acquired immunodeficiency syndrome-associated wasting. Alcohol Clin Exp Res. 2008, 32 (1): 138-147.PubMedCentralCrossRefPubMed

11.

Lewis W: Cardiomyopathy in AIDS: a pathophysiological perspective. Prog Cardiovasc Dis. 2000, 43 (2): 151-170. 10.1053/pcad.2000.9031CrossRefPubMed

12.

Marcondes MC, Watry D, Zandonatti M, Flynn C, Taffe MA, Fox H: Chronic alcohol consumption generates a vulnerable immune environment during early SIV infection in rhesus macaques. Alcohol Clin Exp Res. 2008, 32 (9): 1583-1592. 10.1111/j.1530-0277.2008.00730.xPubMedCentralCrossRefPubMed

13.

Cook RT: Alcohol abuse, alcoholism, and damage to the immune system--a review. Alcohol Clin Exp Res. 1998, 22 (9): 1927-1942.PubMed

14.

Rosenbloom MJ, Sullivan EV, Sassoon SA, O'Reilly A, Fama R, Kemper CA, Deresinski S, Pfefferbaum A: Alcoholism, HIV infection, and their comorbidity: factors affecting self-rated health-related quality of life. J Stud Alcohol Drugs. 2007, 68 (1): 115-125.CrossRefPubMed

15.

Otis JS, Ashikhmin YI, Brown LA, Guidot DM: Effect of HIV-1-related protein expression on cardiac and skeletal muscles from transgenic rats. AIDS Res Ther. 2008, 5: 8- 10.1186/1742-6405-5-8PubMedCentralCrossRefPubMed

16.

Otis JS, Guidot DM: Procysteine stimulates expression of key anabolic factors and reduces plantaris atrophy in alcohol-fed rats. Alcohol Clin Exp Res. 2009, 33 (8): 1450-1459. 10.1111/j.1530-0277.2009.00975.xPubMedCentralCrossRefPubMed

17.

Pruznak AM, Hong-Brown L, Lantry R, She P, Frost RA, Vary TC, Lang CH: Skeletal and cardiac myopathy in HIV-1 transgenic rats. Am J Physiol Endocrinol Metab. 2008, 295 (4): E964-973. 10.1152/ajpendo.90482.2008PubMedCentralCrossRefPubMed

18.

Lang CH, Frost RA, Summer AD, Vary TC: Molecular mechanisms responsible for alcohol-induced myopathy in skeletal muscle and heart. Int J Biochem Cell Biol. 2005, 37 (10): 2180-2195. 10.1016/j.biocel.2005.04.013CrossRefPubMed

19.

Preedy VR, Salisbury JR, Peters TJ: Alcoholic muscle disease: features and mechanisms. Journal of Pathology. 1994, 173 (4): 309-315. 10.1002/path.1711730405CrossRefPubMed

20.

Molina PE, McNurlan M, Rathmacher J, Lang CH, Zambell KL, Purcell J, Bohm RP, Zhang P, Bagby GJ, Nelson S: Chronic alcohol accentuates nutritional, metabolic, and immune alterations during asymptomatic simian immunodeficiency virus infection. Alcohol Clin Exp Res. 2006, 30 (12): 2065-2078. 10.1111/j.1530-0277.2006.00252.xCrossRefPubMed

21.

Ray PE, Liu XH, Robinson LR, Reid W, Xu L, Owens JW, Jones OD, Denaro F, Davis HG, Bryant JL: A novel HIV-1 transgenic rat model of childhood HIV-1-associated nephropathy. Kidney Int. 2003, 63 (6): 2242-2253. 10.1046/j.1523-1755.2003.00028.xCrossRefPubMed

22.

Lassiter C, Fan X, Joshi PC, Jacob BA, Sutliff RL, Jones DP, Koval M, Guidot DM: HIV-1 transgene expression in rats causes oxidant stress and alveolar epithelial barrier dysfunction. AIDS Res Ther. 2009, 6: 1- 10.1186/1742-6405-6-1PubMedCentralCrossRefPubMed

23.

Yadav A, Pati S, Nyugen A, Barabitskaja O, Mondal P, Anderson M, Gallo RC, Huso DL, Reid W: HIV-1 transgenic rat CD4+ T cells develop decreased CD28 responsiveness and suboptimal Lck tyrosine dephosphorylation following activation. Virology. 2006, 353 (2): 357-365. 10.1016/j.virol.2006.05.026CrossRefPubMed

24.

Grody WW, Cheng L, Lewis W: Infection of the heart by the human immunodeficiency virus. Am J Cardiol. 1990, 66 (2): 203-206. 10.1016/0002-9149(90)90589-SCrossRefPubMed

25.

Raidel SM, Haase C, Jansen NR, Russ RB, Sutliff RL, Velsor LW, Day BJ, Hoit BD, Samarel AM, Lewis W: Targeted myocardial transgenic expression of HIV Tat causes cardiomyopathy and mitochondrial damage. Am J Physiol Heart Circ Physiol. 2002, 282 (5): H1672-1678.CrossRefPubMed

26.

Yarasheski KE, Smith SR, Powderly WG: Reducing plasma HIV RNA improves muscle amino acid metabolism. Am J Physiol Endocrinol Metab. 2005, 288 (1): E278-284.PubMedCentralCrossRefPubMed

27.

Otis JS, Brown LA, Guidot DM: Oxidant-induced atrogin-1 and transforming growth factor-beta1 precede alcohol-related myopathy in rats. Muscle Nerve. 2007, 36 (6): 842-848. 10.1002/mus.20883PubMedCentralCrossRefPubMed

28.

Nishikawa J, Sakuma K, Sorimachi Y, Yoshimoto K, Yasuhara M: Increase of Cardiotrophin-1 immunoreactivity in regenerating and overloaded but not denervated muscles of rats. Neuropathology. 2005, 25 (1): 54-65. 10.1111/j.1440-1789.2004.00587.xCrossRefPubMed

29.

Kami K, Morikawa Y, Sekimoto M, Senba E: Gene expression of receptors for IL-6, LIF, and CNTF in regenerating skeletal muscles. J Histochem Cytochem. 2000, 48 (9): 1203-1213. 10.1177/002215540004800904CrossRefPubMed

30.

Spangenburg EE, Booth FW: Leukemia inhibitory factor restores the hypertrophic response to increased loading in the LIF(-/-) mouse. Cytokine. 2006, 34 (3-4): 125-130. 10.1016/j.cyto.2006.05.001CrossRefPubMed

31.

Kim H, Jo C, Jang BG, Oh U, Jo SA: Oncostatin M induces growth arrest of skeletal muscle cells in G1 phase by regulating cyclin D1 protein level. Cell Signal. 2008, 20 (1): 120-129. 10.1016/j.cellsig.2007.09.004CrossRefPubMed

32.

Fujita J, Tsujinaka T, Yano M, Ogawa J, Morita T, Taniguchi H, Shiozaki H, Monden M: [Participation of interleukin-6 to skeletal muscle proteolysis: the effect of IL-6 administration on mRNA expression by the skeletal muscle cell proteolytic system]. Nippon Geka Gakkai Zasshi. 1998, 99 (5): 332.-PubMed

33.

Li YP, Chen Y, John J, Moylan J, Jin B, Mann DL, Reid MB: TNF-alpha acts via p38 MAPK to stimulate expression of the ubiquitin ligase atrogin1/MAFbx in skeletal muscle. FASEB J. 2005, 19 (3): 362-370. 10.1096/fj.04-2364comPubMedCentralCrossRefPubMed

34.

Durieux AC, Amirouche A, Banzet S, Koulmann N, Bonnefoy R, Pasdeloup M, Mouret C, Bigard X, Peinnequin A, Freyssenet D: Ectopic expression of myostatin induces atrophy of adult skeletal muscle by decreasing muscle gene expression. Endocrinology. 2007, 148 (7): 3140-3147. 10.1210/en.2006-1500CrossRefPubMed

35.

Trendelenburg AU, Meyer A, Rohner D, Boyle J, Hatakeyama S, Glass DJ: Myostatin reduces Akt/TORC1/p70S6K signaling, inhibiting myoblast differentiation and myotube size. Am J Physiol Cell Physiol. 2009, 296 (6): C1258-1270. 10.1152/ajpcell.00105.2009CrossRefPubMed

36.

Lang CH, Frost RA, Svanberg E, Vary TC: IGF-I/IGFBP-3 ameliorates alterations in protein synthesis, eIF4E availability, and myostatin in alcohol-fed rats. Am J Physiol Endocrinol Metab. 2004, 286 (6): E916-926. 10.1152/ajpendo.00554.2003CrossRefPubMed

37.

Gilson H, Schakman O, Combaret L, Lause P, Grobet L, Attaix D, Ketelslegers JM, Thissen JP: Myostatin gene deletion prevents glucocorticoid-induced muscle atrophy. Endocrinology. 2007, 148 (1): 452-460.CrossRefPubMed

38.

Amirouche A, Durieux AC, Banzet S, Koulmann N, Bonnefoy R, Mouret C, Bigard X, Peinnequin A, Freyssenet D: Down-regulation of Akt/mammalian target of rapamycin signaling pathway in response to myostatin overexpression in skeletal muscle. Endocrinology. 2009, 150 (1): 286-294.CrossRefPubMed

39.

Sartori R, Milan G, Patron M, Mammucari C, Blaauw B, Abraham R, Sandri M: Smad2 and 3 transcription factors control muscle mass in adulthood. Am J Physiol Cell Physiol. 2009, 296 (6): C1248-1257. 10.1152/ajpcell.00104.2009CrossRefPubMed

40.

Gonzalez-Cadavid NF, Taylor WE, Yarasheski K, Sinha-Hikim I, Ma K, Ezzat S, Shen R, Lalani R, Asa S, Mamita M: Organization of the human myostatin gene and expression in healthy men and HIV-infected men with muscle wasting. Proc Natl Acad Sci USA. 1998, 95 (25): 14938-14943. 10.1073/pnas.95.25.14938PubMedCentralCrossRefPubMed

41.

Spangenburg EE, Brown DA, Johnson MS, Moore RL: Exercise increases SOCS-3 expression in rat skeletal muscle: potential relationship to IL-6 expression. Journal of Physiology. 2006, 572 (Pt 3): 839-848.PubMedCentralCrossRefPubMed

42.

Spangenburg EE, Booth FW: Multiple signaling pathways mediate LIF-induced skeletal muscle satellite cell proliferation. American Journal of Physiology - Cell Physiology. 2002, 283 (1): C204-211.CrossRefPubMed

43.

Lang CH, Wu D, Frost RA, Jefferson LS, Kimball SR, Vary TC: Inhibition of muscle protein synthesis by alcohol is associated with modulation of eIF2B and eIF4E. Am J Physiol. 1999, 277 (2 Pt 1): E268-276.PubMed

44.

Preedy VR, Peters TJ: The effect of chronic ethanol ingestion on protein metabolism in type-I- and type-II-fibre-rich skeletal muscles of the rat. Biochemical Journal. 1988, 254 (3): 631-639.PubMedCentralCrossRefPubMed

45.

Zhang P, Chen X, Fan M: Signaling mechanisms involved in disuse muscle atrophy. Med Hypotheses. 2007, 69 (2): 310-321. 10.1016/j.mehy.2006.11.043CrossRefPubMed

46.

Fernandez-Sola J, Preedy VR, Lang CH, Gonzalez-Reimers E, Arno M, Lin JC, Wiseman H, Zhou S, Emery PW, Nakahara T: Molecular and cellular events in alcohol-induced muscle disease. Alcohol Clin Exp Res. 2007, 31 (12): 1953-1962. 10.1111/j.1530-0277.2007.00530.xCrossRefPubMed

47.

Vary TC, Frost RA, Lang CH: Acute alcohol intoxication increases atrogin-1 and MuRF1 mRNA without increasing proteolysis in skeletal muscle. Am J Physiol Regul Integr Comp Physiol. 2008, 294 (6): R1777-1789. 10.1152/ajpregu.00056.2008PubMedCentralCrossRefPubMed

48.

Chen LH, Huang CY, Osio Y, Fitzpatrick EA, Cohen DA: Effects of chronic alcohol feeding and murine AIDS virus infection on liver antioxidant defense systems in mice. Alcohol Clin Exp Res. 1993, 17 (5): 1022-1028. 10.1111/j.1530-0277.1993.tb05658.xCrossRefPubMed

49.

Chakravarthy MV, Davis BS, Booth FW: IGF-I restores satellite cell proliferative potential in immobilized old skeletal muscle. Journal of Applied Physiology. 2000, 89 (4): 1365-1379.PubMed

Title: Chronic alcohol ingestion exacerbates skeletal muscle myopathy in HIV-1 transgenic rats
Authors: Caroline R Clary
Daniel M Guidot
Margaux A Bratina
Jeffrey S Otis
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: AIDS Research and Therapy / Issue 1/2011
Electronic ISSN: 1742-6405
DOI: https://doi.org/10.1186/1742-6405-8-30

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Findings

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2011

Factors associated with non-adherence to highly active antiretroviral therapy in Nairobi, Kenya

Multiple shRNA combinations for near-complete coverage of all HIV-1 strains

Long-term CD4+ lymphocyte response following HAART initiation in a U.S. Military prospective cohort

The L76V mutation in HIV-1 protease is potentially associated with hypersusceptibility to protease inhibitors Atazanavir and Saquinavir: is there a clinical advantage?

Contraception in HIV-positive female adolescents

Reliability and predictive validity of a hepatitis-related symptom inventory in HIV-infected individuals referred for Hepatitis C treatment

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials