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Endocytosis in Rat Cultured Astrocytes Is Inhibited by Unconjugated Bilirubin

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Abstract

Excessive hyperbilirubinemia can cause irreversible neurological damage in the neonatal period. However, the complete understanding of the pathogenesis of unconjugated bilirubin (UCB) encephalopathy remains a matter of debate. This study investigates whether UCB inhibits the endocytosis of cationized ferritin (CF) by cultured rat astrocytes. The relationship between endocytosis and MTT reduction, as well as changes on tubulin and glial fibrillary acidic protein (GFAP) assembly, were also evaluated. Inhibition of endocytosis was complete in the presence of 171 μM UCB, while a marked decrease of CF labeling was noticed for 86 μM UCB. In addition, MTT reduction was inhibited by 60 to 76% as UCB concentrations changed from 17 to 171 μM, while alterations on both GFAP and microtubule morphology were only achieved by cell exposure to 171 μM UCB. These findings indicate that inhibition of CF endocytosis in rat cortical astrocytes by UCB is a concentration-dependent process that appears to be primarily related to a direct effect on the cell membrane and not to any alteration of cytoskeletal microtubules and intermediate filaments.

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Authors and Affiliations

  1. Centro de Patogénese Molecular, Faculdade de Farmácia, University of Lisbon, 1600-083, Lisbon, Portugal

    Rui F. M. Silva & Dora Brites

  2. Departamento de Zoologia, Faculdade de Ciências, University of Lisbon, 1600-214, Lisbon, Portugal

    Lucinda M. Mata

  3. Instituto Gulbenkian de Ciência, 2780, Oeiras, Portugal

    Sérgio Gulbenkian

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  1. Rui F. M. Silva
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  3. Sérgio Gulbenkian
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Silva, R.F.M., Mata, L.M., Gulbenkian, S. et al. Endocytosis in Rat Cultured Astrocytes Is Inhibited by Unconjugated Bilirubin. Neurochem Res 26, 793–800 (2001). https://doi.org/10.1023/A:1011608017870

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