Effect of HO-1 induction on Leydig Cell proliferation

MONZON, C; PAGOTTO, R; MONDILLO, C; BESIO MORENO, M; PIGNATARO, OP

Congreso; XLVI Reunión Anual de la SAIB; 2010

XLVI Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Heme oxygenase (HO) catalyzes the degradation of heme into three biologically active products: CO, biliverdine and Fe2+. The HO system provides cellular protection through the concerted action of its derivatives involving anti-apoptotic, anti-inflammatory and anti-oxidative mechanisms in many injury and disease models. HO-1 (HO inducible isoform) expression responds to different stressors, pathophysiological states and it is interestingly increased in tumors. We previously reported that HO-1 induction modulates Leydig cell (LC) steroidogenesis and we suggested a cytoprotective effect on these cells.  In this study we aimed to evaluate the effects of HO-1 on LC proliferation. In order to achieve this, we tested different concentrations of hemin (HO-1 inducer) on MA-10 Leydig tumor cells and 33-day old Sprague-Dawley rat LC. Proliferation was assessed by MTT and 3H-Thymidine incorporation assays. Cell viability was tested by Trypan blue exclusion method.  The results indicated that HO-1 inhibits LC proliferation in both experimental models when treated with hemin, in a concentration-dependent manner. Cytotoxic effects were not observed. We suggest that HO-1 would be exerting one of its cytoprotective mechanisms by truncating cell cycle progression through mechanisms still to be elucidated. X814-UBA, PIP5525-CONICET & PICT 05-38281 to OPP.