Oxidative Stress during HIV Infection: Mechanisms and Consequences

Figure 2

Mechanisms of HIV neurotoxicity. Enhanced ROS production, triggered by gp120, Tat, and Vpr proteins that circulate in the blood, results in alteration of blood-brain barrier (BBB) through matrix metalloproteinase 2/9- (MMP2/9-) mediated disruption of tight junction receptors ZO-1, laminin, claudin 5, and occludin. Gp120, Tat, and Vpr proteins activate a consequence of proapoptotic events. They include (i) oxidation of DNA and consequent genomic and mitochondrial DNA instability, (ii) increased lipid peroxidation and accumulation of ceramide that aggravates toxicity, (iii) induction of spermine oxidase (SMO) augmenting oxidative stress and producing toxic acrolein, (iv) stimulation of A-type transient outward K⁺ currents by Kv channels, and (v) induction of proinflammatory cytokines. In addition, it upregulates expression of opioid receptors that contribute to neurotoxicity in HIV-infected drug addicts.