p38 MAP kinase mediates bilirubin-induced neuronal death of cultured rat cerebellar granule neurons

Suizhen Lin, Chong Yan, Xing Wei, Steven M. Paul, Yansheng Du

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Brain damage induced by unconjugated bilirubin, the end product of heme catabolism, in human neonates is a well recognized clinical syndrome. However, the cellular and molecular mechanisms underlying bilirubin neurotoxicity remain unclear. To characterize the sequence of events leading to bilirubin-induced neurotoxicity, we have exposed rat cerebellar granule neurons (CGN) to bilirubin and investigated whether activation of p38 MAP kinase mediates neuronal death. In this study, bilirubin markedly induces an early activation of p38 MAP kinase at 1 h. Pretreatment of neurons with a p38 MAP kinase inhibitor, SB 203580, significantly protected CGN against bilirubin-induced neurotoxicity. Our data suggest that hyperphosphorylation of p38 MAP kinase plays an important role in bilirubin-induced neuronal death and provides a novel approach to discovering drugs to treat bilirubin-induced encephalopathy.

Original languageEnglish
Pages (from-to)209-212
Number of pages4
JournalNeuroscience Letters
Volume353
Issue number3
DOIs
StatePublished - Dec 26 2003

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p38 Mitogen-Activated Protein Kinases
Bilirubin
Neurons
Kernicterus
Heme
Brain
Pharmaceutical Preparations

Keywords

  • Bilirubin
  • Cerebellar granule neuron
  • Neuronal death
  • p38 MAP kinase
  • Rat

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

p38 MAP kinase mediates bilirubin-induced neuronal death of cultured rat cerebellar granule neurons. / Lin, Suizhen; Yan, Chong; Wei, Xing; Paul, Steven M.; Du, Yansheng.

In: Neuroscience Letters, Vol. 353, No. 3, 26.12.2003, p. 209-212.

Research output: Contribution to journalArticle

Lin, Suizhen ; Yan, Chong ; Wei, Xing ; Paul, Steven M. ; Du, Yansheng. / p38 MAP kinase mediates bilirubin-induced neuronal death of cultured rat cerebellar granule neurons. In: Neuroscience Letters. 2003 ; Vol. 353, No. 3. pp. 209-212.
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