HIV-1 gp120-Induced Tubular Epithelial Cell Apoptosis Is Mediated Through p38-MAPK Phosphorylation

Aditi A Kapasi,Geeta Patel,Pravin C Singhal,Nicholas Franki

doi:10.1007/bf03402031

Aditi A Kapasi, Geeta Patel + Show 2 more

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https://doi.org/10.1007/bf03402031

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Abstract

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. 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. 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. Gp120 through interaction with CD4 triggers tubular cell apoptosis. This effect of gp120 on tubular cells is mediated through phosphorylation of p38 MAPK.

Highlights

In the northeastern United States, renal disease has been reported to occur in 10–15% of patients with AIDS [1]
To confirm the role of gp120-induced tubular cell mitogen-activated protein kinase (MAPK) activation, we examined the effect of SB 202190, a selective inhibitor of p38 MAPK, on gp120-induced tubular cell apoptosis
To confirm the role of MAPK activity, we studied the effect of SB 202190, a selective inhibitor of p38 MAPK, on gp120-induced tubular cell P38 MAPK activation

Summary

Introduction

In the northeastern United States, renal disease has been reported to occur in 10–15% of patients with AIDS [1]. The majority of HIV-1 infected patients with renal disease have features typical of HIV-associated nephropathy (HIVAN). Cohen et al [6] showed the presence of HIV genomic material in glomerular and tubular epithelial cells from renal biopsy tissue of HIV-1 infected patients with glomerulosclerosis. Ray et al [8] demonstrated infection of human primary renal tubular epithelial cells with HIV-1. These investigators suggested that entry of HIV-1 into these tubular cells was through a nonCD4 pathway [8]. Conaldi et al [9] in in vitro studies demonstrated that human renal tubular cells express CD4 receptors and HIV-1 kills tubular epithelial cells by triggering an apoptotic pathway. 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

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