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HIV-1 gp120-induced tubular epithelial cell apoptosis is mediated through p38-MAPK phosphorylation
Aditi A Kapasi1, Geeta Patel, Nicholas Franki
1Immunology and Inflammation Center for Excellence, North Shore-Long Island Jewish Research Institute, Manhasset, New York 11040, USA.
Background:
HIV-associated nephropathy is accompanied by significant tubular alterations in the form of tubular cell proliferation, apoptosis, and microcystic dilatation. In the present study we evaluated the role of CD4 receptors in HIV-1-induced tubular cell injury.
Methods:
To confirm the presence of CD4 receptors in tubular cells, immunocytochemical, Western and Northern blot studies were carried out. To determine the downstream effect of CD4 and gp120 interaction, we evaluated the effect of gp120 on tubular cell p38 mitogen-activated protein kinase (MAPK) activity and phosphorylation. To establish causal relationships between gp120, CD4, and p38 MAPK pathways, we studied the effect of anti-CD4 antibody and SB 202190 (an inhibitor of p38 MAPK) on gp120-induced tubular cell apoptosis.
Results:
Proximal tubular cells in culture as well as in intact tissue showed expression of CD4 (immunocytochemical and Western blot studies). Cultured tubular cells also showed mRNA expression for CD4 (Northern blot studies). Gp120, at concentrations of 10-100 ng/ ml, triggered tubular cell apoptosis; however, this effect of gp120 was inhibited by anti-CD4 antibody. SB 202190 also inhibited gp120-induced tubular cell apoptosis. In addition, gp120 promoted tubular cell p38 MAPK phosphorylation in a time- and dose- dependent manner.
Conclusion:
Gp120 through interaction with CD4 triggers tubular cell apoptosis. This effect of gp120 on tubular cells is mediated through phosphorylation of p38 MAPK.
Insights
HIV-1 gp120 protein triggers kidney tubular cell apoptosis by interacting with CD4 receptors. This process involves the p38 mitogen-activated protein kinase (MAPK) pathway, highlighting a key mechanism in HIV-associated nephropathy.
Area of Science:
- Nephrology
- Virology
- Molecular Biology
Background:
- HIV-associated nephropathy involves significant tubular alterations, including cell proliferation, apoptosis, and microcystic dilatation.
- The role of CD4 receptors in HIV-1-induced tubular cell injury remains to be fully elucidated.
Purpose of the Study:
- To investigate the presence and function of CD4 receptors in renal tubular cells.
- To determine the mechanism by which HIV-1 gp120 induces tubular cell apoptosis, focusing on the p38 MAPK pathway.
Main Methods:
- Immunocytochemical, Western blot, and Northern blot studies were used to confirm CD4 receptor expression in tubular cells.
- The effect of gp120 on tubular cell p38 MAPK activity and phosphorylation was evaluated.
- The impact of anti-CD4 antibody and a p38 MAPK inhibitor (SB 202190) on gp120-induced apoptosis was assessed.
Main Results:
- CD4 receptors and mRNA were detected in proximal tubular cells, both in culture and intact tissue.
- HIV-1 gp120 induced tubular cell apoptosis in a dose-dependent manner.
- Gp120-induced apoptosis was inhibited by anti-CD4 antibody and SB 202190, and gp120 promoted p38 MAPK phosphorylation.
Conclusions:
- HIV-1 gp120 interacts with CD4 receptors on tubular cells to trigger apoptosis.
- The observed apoptosis is mediated by the phosphorylation of the p38 MAPK pathway.