CURCUMIN AND HEME OXYGENASE-1 EFFECTS ON LEYDIG CELLS STEROIDOGENESIS AND PROLIFERATION

RAICES, TRINIDAD; PEREYRA ELBA N; VARELA, MARÍA LUISA; PIGNATARO OMAR P; BESIO MORENO MARCOS

Buenos Aires

Congreso; XX ANNUAL MEETING OF THE ARGENTINEAN BIOLOGY SOCIETY (SAB) and XVII MEETING OF THE URUGUAYAN SOCIETY OF BIOSCIENCES (SUB); 2018

Sociedad Argentina de Biología (SAB)

A23 CURCUMIN AND HEME OXYGENASE-1 EFFECTS ON LEYDIG CELLS STEROIDOGENESIS AND PROLIFERATION Raices T1, Varela ML1, Besio Moreno M1, Pereyra EN1, Pignataro OP1,2. 1 Institute of Biology and Experimental Medicine (IBYME-CONICET). 2 Department of Biological Chemistry, School of Sciences, University of Buenos Aires. E-mail: triniraices@hotmail.com Curcumin (CUR) or diferuloylmethane is a bioactive component of turmeric, a food additive derived from the rhizome of the plant Curcuma longa. This dietary polyphenol is the subject of countless studies since it has proven to have both prophylactic and therapeutic effects on illnesses as diverse as cancer, diabetes, cardiomyopathies, chronic pain and neurodegenerative diseases. One of its mechanisms of action is the activation of antioxidant pathways. Given that there is not much information about how it affects the endocrine population of the testis, the Leydig cells (LCs), we aimed to describe CUR effects on MA-10 tumoral cell line steroidogenesis and proliferation. On the other hand, we sought to clarify its interaction with one of the most important antioxidant enzymes, heme oxygenase-1 (HO-1). After a 5-h incubation with growing concentrations of CUR, we assessed progesterone production by radioimmunoassay and found that CUR stimulates LCs steroidogenesis at 20-40 μM concentrations and inhibits steroidogenesis at 80-100 μM. This inhibition correlates with a marked alteration of cell morphology and a significant decrease in cell viability as evaluated by trypan blue exclusion assay. Secondly, cell proliferation was assessed after a 24-h incubation period using the sulphorhodamine B assay. CUR has a positive effect at 20 μM concentration and decreases proliferation at 80-100 μM. We have previously described HO-1 negative effect on MA-10 steroidogenesis and proliferation. Cells were incubated for 5 h with CUR and subjected to Western blot assay. CUR augments basal HO-1 protein levels in a concentration dependent fashion. CUR also enhances HO-1 expression when stimulated with hemin, its inducer. What?s more, if LCs are preincubated for 1 h with CUR and then subjected to a 5-h incubation with hemin, CUR can partially revert HEM negative effect on steroidogenesis provided that hemin does not induce HO-1 to such extent that it completely abrogates steroidogenesis regulation. The results presented herein contribute to the understanding on how curcumin regulates MA-10 cells functions and how it can impair them if present in high concentrations. Besides, we show that depending on how strong the stimuli upregulating HO-1 expression is, CUR can act as a protective agent reverting the negative effect of this enzyme on steroidogenesis.