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

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Abstract

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 (immunocyto-chemical 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.

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Acknowledgment

The present study was supported by the grant RO1 DA 12111 from the National Institutes of Health. Part of this work was presented at the 31st, 32nd, and 33rd Annual Meetings of the American Society of Nephrology.

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Authors and Affiliations

  1. Immunology and Inflammation Center for Excellence, North Shore-Long Island Jewish Research Institute, Manhasset, New York, USA

    Pravin C. Singhal MD

  2. Division of Kidney Diseases and Hypertension, Long Island Jewish Medical Center, New Hyde Park, New York, 11040, USA

    Aditi A. Kapasi, Geeta Patel, Nicholas Franki & Pravin C. Singhal MD

Authors
  1. Aditi A. Kapasi
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  2. Geeta Patel
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  3. Nicholas Franki
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  4. Pravin C. Singhal MD
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Correspondence to Pravin C. Singhal MD.

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Kapasi, A.A., Patel, G., Franki, N. et al. HIV-1 gp120-Induced Tubular Epithelial Cell Apoptosis Is Mediated Through p38-MAPK Phosphorylation. Mol Med 8, 676–685 (2002). https://doi.org/10.1007/BF03402031

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