Induction of highly proliferative phenotypes in cultured glomerular mesangial cells by benzo[a]pyrene alone or in combination with methoxamine

Russell C. Bowes, Thomas J. Weber, Kenneth S. Ramos

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Recent studies have suggested that aromatic hydrocarbons can initiate glomerular mesangial cell (GMC) injury and contribute to the onset of renal disease. The present studies were conducted to assess the impact of benzo[a]pyrene (BaP), a ubiquitous polycyclic aromatic hydrocarbon, on the proliferation of GMCs. Challenge of cultured GMCs with BaP (0.3-30 μM) for 24 h was associated with concentration-dependent decreases in DNA synthesis, a response mediated by selective interference with early G1cell cycle progression. One cycle of sequential treatment with 3 μMBaP for 24 h followed by challenge with 10 μMmethoxamine (MeoA), a growth-promoting α1-adrenergic agonist, for an additional 24 h attenuated the inhibitory response elicited by BaP alone. Following three rounds of sequential treatment with BaP and MeoA, GMCs exposed to BaP alone or BaP/MeoA exhibited enhanced proliferation rates relative to controls. BaP/MeoA cells acquired the greatest proliferative enhancement and exhibited unregulated c-jun and c-fos gene expression under growth-arrested and serum-stimulated conditions. Marked increases in specific AP-1 binding to a synthetic oligonucleotide were observed upon serum stimulation of quiescent cultures of BaP/MeoA cells relative to controls or any of the other treatment groups. These data demonstrate that sequential treatment with BaP in combination with MeoA is associated with induction of highly proliferative phenotypes in GMCs characterized by differential expression of growth-related protooncogenes.

Original languageEnglish (US)
Pages (from-to)243-250
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume323
Issue number2
DOIs
StatePublished - Nov 10 1995
Externally publishedYes

Keywords

  • Benzo[a]pyrene
  • C-jun
  • Cell proliferation
  • Glomerular mesangial cells
  • Methoxamine
  • TCDD

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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