CONICET | Buscador de Institutos y Recursos Humanos

Bilirubin modulates cell cycle in rat cerebella Robert, M.C; Gazzin, S.; Berengeno, A.; Bellarosa, C.; Tiribelli, C. Fondazione Italiana Fegato- Area Science Park Basovizza and department of ACADEM University of Trieste, Trieset, Italy. celeste.robert@csf.units.it Keywords: Bilirubin- Cell cycle- cerebella hypoplasia- Gunn rat- Crigler-Najjar type I Syndrome High levels of unconjugated bilirubin (UCB) in plasma can lead to accumulation of bilirubin in the brain as occurs in the inherited deficiency of hepatic UDP-glucuronosyltransferase 1A1 (Crigler-Najjar type I Syndrome) or to its immaturity in neonates. The Gunn rat represents the animal model for the condition. Homozygous hyperbilirubinemic jj Gunn rats develop marked cerebellar hypoplasia with the greatest damage occurring in brain areas that mature postnatally. Recently, an effect of UCB on cell cycle progression has been described with cell cycle arrest in the late G1 phase. The aim of this study was to investigate if the cerebellar hypoplasia observed in jj Gunn rat could be caused by UCB by cell cycle arrest. The cerebella from hyperbilirubinemic (jj) and normal (JJ) Gunn rat at 9 days after birth was dissected and divided in two parts. The first was used to evaluated the mRNA relative expression of Cyclin A, D1, E, and Cdk2 genes using Real Time q-PCR (n=11); and the other one to determinate the protein levels of Cdk2 and Cyclin A by quantitative Western Blot (n=9 and n=4 respectively). At mRNA level, we observed a slight reduction in Cyclin D1 expression in jj rats (JJ 1.00 ± 0.18 vs. jj 0.80 ± 0.30) and a significant increase in the Cyclin E expression (JJ 1.00 ± 0.34 vs. jj 1.44 ± 0.26, ** p < 0.01). The mRNA expression of Cyclin A and Cdk2 was unchanged. The protein relative expression of Cdk2 was significantly reduced in jj animals (JJ 1.12 ± 0.11 vs. jj 0.84 ± 0.07 *** p

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