| Autor: |
Pandhare, Jui, Addai, Amma B., Mantri, Chinmay K., Hager, Cynthia, Smith, Rita M., Barnett, Louis, Villalta, Fernando, Kalams, Spyros A., Dash, Chandravanu |
| Zdroj: |
American Journal of Pathology; April 2014, Vol. 184 Issue: 4 p927-936, 10p |
| Abstrakt: |
Substance abuse is a major barrier in eradication of the HIV epidemic because it serves as a powerful cofactor for viral transmission, disease progression, and AIDS-related mortality. Cocaine, one of the commonly abused drugs among HIV-1 patients, has been suggested to accelerate HIV disease progression. However, the underlying mechanism remains largely unknown. Therefore, we tested whether cocaine augments HIV-1–associated CD4+T-cell decline, a predictor of HIV disease progression. We examined apoptosis of resting CD4+T cells from HIV-1–negative and HIV-1–positive donors in our study, because decline of uninfected cells plays a major role in HIV-1 disease progression. Treatment of resting CD4+T cells with cocaine (up to 100 µmol/L concentrations) did not induce apoptosis, but 200 to 1000 µmol/L cocaine induced apoptosis in a dose-dependent manner. Notably, treatment of CD4+T cells isolated from healthy donors with both HIV-1 virions and cocaine significantly increased apoptosis compared with the apoptosis induced by cocaine or virions alone. Most important, our biochemical data suggest that cocaine induces CD4+T-cell apoptosis by increasing intracellular reactive oxygen species levels and inducing mitochondrial depolarization. Collectively, our results provide evidence of a synergy between cocaine and HIV-1 on CD4+T-cell apoptosis that may, in part, explain the accelerated disease observed in HIV-1–infected drug abusers. |
| Databáze: |
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