Tags

Type your tag names separated by a space and hit enter

Regulation of c-Jun N-terminal kinase, p38 kinase and AP-1 DNA binding in cultured brain neurons: roles in glutamate excitotoxicity and lithium neuroprotection.
J Neurochem. 2003 Feb; 84(3):566-75.JN

Abstract

In rat cerebellar granule cells, glutamate induced rapid activation of c-Jun N-terminal kinase (JNK) and p38 kinase to phosphorylate c-Jun (at Ser63) and p53 (at Ser15), respectively, and a subsequent marked increase in activator protein-1 (AP-1) binding that preceded apoptotic death. These glutamate-induced effects and apoptosis could largely be prevented by long-term (7 days) pretreatment with 0.5-2 mm lithium, an antibipolar drug. Glutamate's actions could also be prevented by known blockers of this pathway, MK-801 (an NMDA receptor blocker), SB 203580 (a p38 kinase inhibitor) and curcumin (an AP-1 binding inhibitor). The concentration- and time-dependent suppression of glutamate's effects by lithium and curcumin correlated well with their neuroprotective effects. These results suggest a prominent role of JNK and p38, as well as their downstream AP-1 binding activation and p53 phosphorylation in mediating glutamate excitotoxicity. Moreover, the neuroprotective effects of lithium are mediated, at least in part, by suppressing NMDA receptor-mediated activation of the mitogen-activated protein kinase pathway.

Authors+Show Affiliations

Chen RW
Molecular Neurobiology Section, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.
Qin ZH
No affiliation info available
Ren M
No affiliation info available
Kanai H
No affiliation info available
Chalecka-Franaszek E
No affiliation info available
Leeds P
No affiliation info available
Chuang DM
No affiliation info available

MeSH

AnimalsApoptosisCells, CulturedCerebellumDNAEnzyme ActivationEnzyme InhibitorsExcitatory Amino Acid AntagonistsGlutamic AcidJNK Mitogen-Activated Protein KinasesLithiumMAP Kinase Signaling SystemMitogen-Activated Protein KinasesNeuronsNeuroprotective AgentsPhosphorylationProtein BindingRatsRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateTimeTranscription Factor AP-1Tumor Suppressor Protein p53p38 Mitogen-Activated Protein Kinases

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12558976

Citation

Chen, Ren-Wu, et al. "Regulation of c-Jun N-terminal Kinase, P38 Kinase and AP-1 DNA Binding in Cultured Brain Neurons: Roles in Glutamate Excitotoxicity and Lithium Neuroprotection." Journal of Neurochemistry, vol. 84, no. 3, 2003, pp. 566-75.
Chen RW, Qin ZH, Ren M, et al. Regulation of c-Jun N-terminal kinase, p38 kinase and AP-1 DNA binding in cultured brain neurons: roles in glutamate excitotoxicity and lithium neuroprotection. J Neurochem. 2003;84(3):566-75.
Chen, R. W., Qin, Z. H., Ren, M., Kanai, H., Chalecka-Franaszek, E., Leeds, P., & Chuang, D. M. (2003). Regulation of c-Jun N-terminal kinase, p38 kinase and AP-1 DNA binding in cultured brain neurons: roles in glutamate excitotoxicity and lithium neuroprotection. Journal of Neurochemistry, 84(3), 566-75.
Chen RW, et al. Regulation of c-Jun N-terminal Kinase, P38 Kinase and AP-1 DNA Binding in Cultured Brain Neurons: Roles in Glutamate Excitotoxicity and Lithium Neuroprotection. J Neurochem. 2003;84(3):566-75. PubMed PMID: 12558976.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of c-Jun N-terminal kinase, p38 kinase and AP-1 DNA binding in cultured brain neurons: roles in glutamate excitotoxicity and lithium neuroprotection. AU - Chen,Ren-Wu, AU - Qin,Zheng-Hong, AU - Ren,Ming, AU - Kanai,Hirohiko, AU - Chalecka-Franaszek,Elzbieta, AU - Leeds,Peter, AU - Chuang,De-Maw, PY - 2003/2/1/pubmed PY - 2003/2/15/medline PY - 2003/2/1/entrez SP - 566 EP - 75 JF - Journal of neurochemistry JO - J Neurochem VL - 84 IS - 3 N2 - In rat cerebellar granule cells, glutamate induced rapid activation of c-Jun N-terminal kinase (JNK) and p38 kinase to phosphorylate c-Jun (at Ser63) and p53 (at Ser15), respectively, and a subsequent marked increase in activator protein-1 (AP-1) binding that preceded apoptotic death. These glutamate-induced effects and apoptosis could largely be prevented by long-term (7 days) pretreatment with 0.5-2 mm lithium, an antibipolar drug. Glutamate's actions could also be prevented by known blockers of this pathway, MK-801 (an NMDA receptor blocker), SB 203580 (a p38 kinase inhibitor) and curcumin (an AP-1 binding inhibitor). The concentration- and time-dependent suppression of glutamate's effects by lithium and curcumin correlated well with their neuroprotective effects. These results suggest a prominent role of JNK and p38, as well as their downstream AP-1 binding activation and p53 phosphorylation in mediating glutamate excitotoxicity. Moreover, the neuroprotective effects of lithium are mediated, at least in part, by suppressing NMDA receptor-mediated activation of the mitogen-activated protein kinase pathway. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/12558976/Regulation_of_c_Jun_N_terminal_kinase_p38_kinase_and_AP_1_DNA_binding_in_cultured_brain_neurons:_roles_in_glutamate_excitotoxicity_and_lithium_neuroprotection_ DB - PRIME DP - Unbound Medicine ER -