TY - JOUR
T1 - p38 MAP kinase mediates bilirubin-induced neuronal death of cultured rat cerebellar granule neurons
AU - Lin, Suizhen
AU - Yan, Chong
AU - Wei, Xing
AU - Paul, Steven M.
AU - Du, Yansheng
PY - 2003/12/26
Y1 - 2003/12/26
N2 - 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.
AB - 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.
KW - Bilirubin
KW - Cerebellar granule neuron
KW - Neuronal death
KW - Rat
KW - p38 MAP kinase
UR - http://www.scopus.com/inward/record.url?scp=0344234422&partnerID=8YFLogxK
U2 - 10.1016/j.neulet.2003.09.053
DO - 10.1016/j.neulet.2003.09.053
M3 - Article
C2 - 14665418
AN - SCOPUS:0344234422
SN - 0304-3940
VL - 353
SP - 209
EP - 212
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 3
ER -