N-acetylcysteine reverses cardiac myocyte dysfunction in HIV-Tat proteinopathy

Journal of Applied Physiology
Fangping ChenMitchell S Finkel

Abstract

HIV cardiomyopathy remains highly prevalent among the estimated 33 million HIV-infected individuals worldwide. This is particularly true in developing countries. Potential mechanisms responsible for myocardial dysfunction following HIV infection include direct effects of HIV proteins. We have previously reported that cardiac myocyte-specific expression of HIV-Tat (Tat) results in a murine cardiomyopathy model. We now report that Tat exhibits decreased myocardial ATP [wild type (WT) vs. Tat transgenic (TG), P < 0.01] and myocyte GSH levels (WT vs. TG, P < 0.01), decreased GSH/GSSG ratio (WT vs. TG, P < 0.01), increased H(2)O(2) levels (WT vs. TG, P < 0.05), and increased catalase (TG vs. WT, P < 0.05) and GPX1 (glutathione peroxidase 1) activities (WT vs. TG, P < 0.05), blunted cardiac myocyte positive inotropy (% peak shortening, WT vs. TG, P < 0.01; +dl/dt, WT vs. TG, P < 0.01) and negative inotropy (-dl/dt, WT vs. TG, P < 0.01), and blunted inotropic responses to Ca(2+) (P < 0.01, for each) and shortened anatomical and functional survival in vitro (P < 0.01). The sulfhydryl donor, N-acetylcysteine (NAC; 10(-4) M), completely reversed both the positive and negative inotropic defects in Tat; increased GSH (P < 0.01) and GSH/GSS...Continue Reading

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Citations

Aug 27, 2013·Critical Reviews in Immunology·Alexander J Gill, Dennis L Kolson
Oct 10, 2013·American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions·Azita Hajhossein TalasazFarzad Darabi
Sep 21, 2013·Cardiovascular Toxicology·Luciana Grazziotin RossatoFernando Remião
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Oct 7, 2017·Current Opinion in HIV and AIDS·Roger C McIntoshBarry E Hurwitz
Jun 1, 2013·Journal of Applied Physiology·Fangping ChenMitchell S Finkel

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