کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2602141 1133364 2007 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Phosphatidylinositol-3 kinase/Akt/p70S6K/AP-1 signaling pathway mediated benzo(a)pyrene-induced cell cycle alternation via cell cycle regulatory proteins in human embryo lung fibroblasts
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Phosphatidylinositol-3 kinase/Akt/p70S6K/AP-1 signaling pathway mediated benzo(a)pyrene-induced cell cycle alternation via cell cycle regulatory proteins in human embryo lung fibroblasts
چکیده انگلیسی

Benzo(a)pyrene (B(a)P), a potent environmental procarcinogen, has been shown to cause cell cycle alternation. However, the mechanisms involved in this effect are not well understood yet. Our current results demonstrated that B(a)P exposure led to cell proliferation and a 33.5% increase in S phase cells as well as a 26.8% decrease in G1 phase cells in human embryo lung fibroblasts (HELFs). Those cell cycle alternations were accompanied with transactivation of activator protein-1 (AP-1) and phosphorylation of Akt and p70S6K. These changes were blocked by overexpression of dominant negative mutants of phosphatidylinositol-3 kinase (Δp85) or Akt (DN-Akt), respectively. Moreover, pretreatment of cells with rapamycin, a specific p70S6K inhibitor, inhibited B(a)P-induced AP-1 activation, cell cycle alteration and phosphorylation of p70S6K, but had no effect on Akt phosphorylation. Our results, therefore, suggest that phosphatidylinositol-3 kinase (PI-3K)/Akt/p70S6K/AP-1 pathway participates in B(a)P-induced cell cycle alternations. Furthermore, we explored the effect of this pathway on cell cycle regulatory proteins. B(a)P markedly increases in the expression of cyclin D1 and E2F1 and phosphorylation of retinoblastoma protein (Rb). In addition, we found that inactivation of PI-3K, Akt or p70S6K could eliminate those effects on cell cycle regulatory proteins. Collectively, PI-3K/Akt/p70S6K/AP-1 pathway mediated B(a)P-induced alternation of cell cycle through regulation of cell cycle regulatory proteins such as cyclin D1, E2F1, and Rb in HELFs.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 170, Issue 1, 5 April 2007, Pages 30–41
نویسندگان
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