title: HIV-1 gp120-induced tubular epithelial cell apoptosis is mediated through p38-MAPK phosphorylation.
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 (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.
  
  
  CONCLUSIONS
  Gp120 through interaction with CD4 triggers tubular cell apoptosis. This effect of gp120 on tubular cells is mediated through phosphorylation of p38 MAPK.
authors.affiliation: Immunology and Inflammation Center for Excellence, North Shore-Long Island Jewish Research Institute, Manhasset, New York 11040, USA.
authors.forename: Aditi A
authors.initials: AA
authors.lastname: Kapasi
authors.forename: Geeta
authors.initials: G
authors.lastname: Patel
authors.forename: Nicholas
authors.initials: N
authors.lastname: Franki
authors.forename: Pravin C
authors.initials: PC
authors.lastname: Singhal
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D015152:Blotting, Northern; D015153:Blotting, Western; D015704:CD4 Antigens / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D015497:HIV-1; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010446:Peptide Fragments / Q000276:immunology; D010766:Phosphorylation; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D015704:CD4 Antigens; D004791:Enzyme Inhibitors; D015699:HIV Envelope Protein gp120; D007093:Imidazoles; D010446:Peptide Fragments; D018809:Proliferating Cell Nuclear Antigen; D011725:Pyridines; D012333:RNA, Messenger; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole