NF-kB activation is involved in tumoural regression process induced by Bromocriptine in pituitary

PALMERI C.; PETITI J.P.; SOSA L.; MUKDSI J. H.; GUTIÉRREZ S.; DE PAUL A.L.; TORRES A.I.

Buenos Aires

Congreso; III Iberoamerican Congress of NeuroImmunoModulation; 2008

Previously we demonstrated that Bromocriptine (BC) induced tumor regression mainly by a non-apoptotic cell death also dubbed paraptosis, characterized by cytoplasmic vacuolization on expense to endoplasmic reticulum (ER) and mitochondria swelling. Under stress conditions, the ER initiates pathways signal alarm with NF-kB activation that requires IkBá dissociation and finally triggers cell suicide. The purpose of the present study was to examine whether NF-kB is involved in paraptosis induced by BC in hyperoplastic pituitaries. Male rats were estrogenized with estradiol benzoate (15mg) for 30d (E), and the last 5d, BC was administered (0,3mg/100g/d) (E+Bc). Control group without treatment (C). Cell death characterization was analyzed by Electron Microscopy (EM). NF-kB was studied by Immunocytochemistry at EM. Statistical analysis: ANOVA-Fisher. In cytoplasmic fractions BC significantly increased NF-kB expression with a consequent diminution of IkBalpha (p<0.01 vs. E). At nuclear compartment, BC also induced an augment in NF-kB expression levels (p<0.01 vs. C and E) that was correlated with an intense immunogold labelling in pituitary cells by EM. These results suggest that BC induced the NF-kB activation and translocation to nucleus of pituitary cells triggering paraptosis cell death.