HIV-1 Transactivator Protein Induces ZO-1 and Neprilysin Dysfunction in Brain Endothelial Cells via the Ras Signaling Pathway

Figure 4

Role of Ras signaling in HIV-1 Tat-induced accumulation of exogenous Aβ in HBEC-5i. HIV-1 Tat exposure markedly increased the accumulation of Aβ (1–40) HiLyte in HBEC-5i. Pretreatment with 5 μmol/L FTS for 3 h followed by coexposure to HIV-1 Tat and FTS significantly decreased Aβ (1–40) HiLyte accumulation (a). FTS inhibited HIV-1 Tat-induced transendothelial transfer of Aβ. Confluent HBEC-5i cells in Transwell filter inserts were exposed to 1 μmol/L Aβ (1–40) HiLyte for the last 20 min of HIV-1 Tat exposure in the upper chamber, mimicking the blood side of the BBB. The fluorescence signal of Aβ (1–40) HiLyte was measured in the lower chamber, equivalent to the brain side of the BBB (b). Data are expressed as means ± standard error of the mean (). versus that in the control; ^# versus that in HIV-1 Tat.

(a)

(b)