Caveolin‐1 is involved in HIV‐1 Tat‐induced activation of the Ras signaling and alterations of tight junction protein expression in human brain microvascular endothelial cells

HIV Tat protein is released by acutely HIV‐1‐infected cells and can affect the integrity of the brain endothelium and the blood‐brain barrier by induction of redox‐activated signaling. Caveolae serve as the signaling platforms that co‐localize various signaling components, including the Ras and Rho signaling cascades. These pathways are critical for the integrity of the BBB, because they regulate the rearrangement of cytoskeleton and permeability of cell junctions. Therefore, the present study was focused on the effects of Tat on the Ras and Rho signaling pathways. Treatment with Tat markedly activated Ras and RhoA levels in cultured human BMEC. Interestingly, caveolin‐1 protein levels were upregulated in parallel to Ras and Rho activation. Silencing caveolin‐1 by specific siRNA resulted in diminished activation of Ras but not RhoA in response to Tat. Several tight junction proteins, such as ZO‐1, occludin, and claudin‐1, were significantly decreased in caveolar fractions of human BMEC upon Tat stimulation. The present data indicate the importance of caveolar‐mediated signaling in response to Tat exposure. Supported by MH63022, MH072567 , and NS39254.