Modulation of Cell Cycle Progression in the Spermatocyte Cell Line [GC-2spd(ts) Cell-Line] by Cigarette Smoke Condensate (CSC) via Arylhydrocarbon Receptor-Nuclear Factor Erythroid 2-Related Factor 2 (Ahr-Nrf2) Pathway. Issue 1 (1st January 2014)

• Record Type: Journal Article
• Authors: Esakky, Prabagaran; Hansen, Deborah A.; Drury, Andrea M.; Moley, Kelle H.
• Is Part Of: Biology of reproduction. Volume 90:Issue 1(2014)
• Publication Date: 2014-01-01
• Subjects: Ahr -- CSC -- cell cycle -- Nrf2 -- spermatocytes; Reproduction -- Periodicals; Biology; Reproduction; Reproduction; Electronic journals; Periodicals; Periodicals; 571.805
• DOI: 10.1095/biolreprod.113.113225
• Languages: English
• ISSNs: 0006-3363

Abstract

Abstract: Prior studies in our laboratory have demonstrated that cigarette smoke condensate (CSC) activates arylhydrocarbon receptor ( Ahr ) leading to upregulation of several antioxidant enzymes in murine spermatocytes. In this study, we show that exposure of the spermatocyte cell line GC-2spd(ts) to CSC induces an increase in Cyp1a1, demonstrating AHR activation, and simultaneous expression and nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2), where it is believed to modulate Ahr expression by a feedback mechanism. Pharmacological inhibition by the AHR-antagonist CH223191 and interference by Ahr - and Nrf2 -small interfering RNA followed by quantitative real-time PCR implicate the Ahr-Nrf2 pathway in the modulation of DNA damage and growth suppression genes such as Gadd45a and P21 and oxidative stress-related genes Cyp1a1, Nrf2, and Ahrr . Flow cytometry accompanied with cell proliferation assay indicate the CSC induces accumulation of spermatocytes at the S-G2/M phase of the cell cycle. Thus, the data obtained suggest that CSC contains several AHR-agonists that are capable of altering the growth pattern of spermatocytes in vitro through the Ahr-Nrf2 signaling mechanism.