Does Bilirubin affect the ABCc (Mrp1) expression in the brain of the Gunn rat

ANDREA L. BERENGENO; SILVIA GAZZIN; CRISTINA BELLAROSA; M. CELESTE ROBERT; CLAUDIO TIRIBELLI

Copenhagen

Congreso; 3rd Congress of the European Academy of Paediatric Societies (EAPS); 2010

DOES BILIRUBIN AFFECT THE ABCC1 (MRP1) EXPRESSION IN THE BRAIN PARENCHYMA OF THE GUNN RAT? A. Berengeno, S. Gazzin, C. Bellarosa, M.C. Robert, C. Tiribelli Liver Italian Foundation, Trieste, Italy Background: In infants severe unconjugated hyperbilirubinemia can produce brain bilirubin (UCB) accumulation leading to neurological damage (Kernicterus). ABCc1 (Mrp1), an ABC transporter family with high affinity for UCB protects neural cells from UCB toxicity in vitro. Aim: To compare in vivo Mrp1 protein and gene expression in UCB damaged (cerebellum: Cll, striatum: St) and not damaged (cerebral cortex: Cx, hippocampus: Hip) regions of CNS in normal (JJ) and hyperbilirubinemic (jj) Gunn rats. Methods: Quantitative Western blot and RT-qPCR were performed in Cll, St, Cx and Hip of JJ and jj rats 9 days after birth. Results: In JJ animals, Mrp1 protein was similar in Cll, St and Hip; in Cx the expression was lower (p< .05). No difference was found in Mrp1 protein level in Cll and St in jj respect to JJ animals while a decrease (p< .05) was observed in the Hip. On the contrary, a significant increase (p < .05) of Mrp1 protein expression was detected in Cx of jj animals. At mRNA level, similar values were obtained in all tissues dissected from either JJ or jj animals with the exception of a decrease (p< .05) in Hip. Conclusions: The lack of correlation between Mrp1 (protein and mRNA level) and UCB-related neurological damage suggests that in vivo this transporter is not a major player in UCB-induced neurological damage.