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Activating transcription factor 3 up-regulated by c-Jun NH(2)-terminal kinase/c-Jun contributes to apoptosis induced by potassium deprivation in cerebellar granule neurons.
Neuroscience. 2008 Feb 06; 151(3):771-9.N

Abstract

Cerebellar granule neurons (CGNs) depend on potassium depolarization for survival and undergo apoptosis when deprived of depolarizing concentration of potassium. Activating transcription factor 3 (ATF3), a stress-inducible protein, belongs to the ATF/CREB family of transcription factors family and is involved in cell growth and apoptosis. However, the role of ATF3 in neuronal apoptosis remains unknown. Here, we showed that ATF3 was up-regulated under potassium deprivation in CGNs, and this induction was preceded by a rapid and sustained activation of c-Jun NH(2)-terminal kinase/c-Jun signaling pathway, which plays a fundamental role in neuronal apoptosis. Furthermore, ATF3 up-regulation was abolished by inhibition of JNK or knockdown of c-Jun. Finally, knockdown of ATF3 by RNA interference protected CGNs from potassium deprivation-induced apoptosis. Taken together, our results indicate that ATF3 is a downstream target of JNK/c-Jun pathway and contributes to apoptosis induced by potassium deprivation in rat CGNs.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Mei Y
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Road II, Guangzhou 510080, China.
Yuan Z
No affiliation info available
Song B
No affiliation info available
Li D
No affiliation info available
Ma C
No affiliation info available
Hu C
No affiliation info available
Ching YP
No affiliation info available
Li M
No affiliation info available

MeSH

Activating Transcription Factor 3AnimalsAnimals, NewbornApoptosisCells, CulturedCerebellumDose-Response Relationship, DrugDrug InteractionsEnzyme InhibitorsGalactosidesGreen Fluorescent ProteinsJNK Mitogen-Activated Protein KinasesLuciferasesNeuronsPotassium ChloridePotassium DeficiencyRNA, Small InterferingRatsRats, Sprague-DawleyTransfectionUp-Regulation

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18178318

Citation

Mei, Y, et al. "Activating Transcription Factor 3 Up-regulated By c-Jun NH(2)-terminal kinase/c-Jun Contributes to Apoptosis Induced By Potassium Deprivation in Cerebellar Granule Neurons." Neuroscience, vol. 151, no. 3, 2008, pp. 771-9.
Mei Y, Yuan Z, Song B, et al. Activating transcription factor 3 up-regulated by c-Jun NH(2)-terminal kinase/c-Jun contributes to apoptosis induced by potassium deprivation in cerebellar granule neurons. Neuroscience. 2008;151(3):771-9.
Mei, Y., Yuan, Z., Song, B., Li, D., Ma, C., Hu, C., Ching, Y. P., & Li, M. (2008). Activating transcription factor 3 up-regulated by c-Jun NH(2)-terminal kinase/c-Jun contributes to apoptosis induced by potassium deprivation in cerebellar granule neurons. Neuroscience, 151(3), 771-9. https://doi.org/10.1016/j.neuroscience.2007.10.057
Mei Y, et al. Activating Transcription Factor 3 Up-regulated By c-Jun NH(2)-terminal kinase/c-Jun Contributes to Apoptosis Induced By Potassium Deprivation in Cerebellar Granule Neurons. Neuroscience. 2008 Feb 6;151(3):771-9. PubMed PMID: 18178318.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activating transcription factor 3 up-regulated by c-Jun NH(2)-terminal kinase/c-Jun contributes to apoptosis induced by potassium deprivation in cerebellar granule neurons. AU - Mei,Y, AU - Yuan,Z, AU - Song,B, AU - Li,D, AU - Ma,C, AU - Hu,C, AU - Ching,Y-P, AU - Li,M, Y1 - 2007/12/04/ PY - 2007/06/05/received PY - 2007/10/04/revised PY - 2007/11/28/accepted PY - 2008/1/8/pubmed PY - 2008/6/13/medline PY - 2008/1/8/entrez SP - 771 EP - 9 JF - Neuroscience JO - Neuroscience VL - 151 IS - 3 N2 - Cerebellar granule neurons (CGNs) depend on potassium depolarization for survival and undergo apoptosis when deprived of depolarizing concentration of potassium. Activating transcription factor 3 (ATF3), a stress-inducible protein, belongs to the ATF/CREB family of transcription factors family and is involved in cell growth and apoptosis. However, the role of ATF3 in neuronal apoptosis remains unknown. Here, we showed that ATF3 was up-regulated under potassium deprivation in CGNs, and this induction was preceded by a rapid and sustained activation of c-Jun NH(2)-terminal kinase/c-Jun signaling pathway, which plays a fundamental role in neuronal apoptosis. Furthermore, ATF3 up-regulation was abolished by inhibition of JNK or knockdown of c-Jun. Finally, knockdown of ATF3 by RNA interference protected CGNs from potassium deprivation-induced apoptosis. Taken together, our results indicate that ATF3 is a downstream target of JNK/c-Jun pathway and contributes to apoptosis induced by potassium deprivation in rat CGNs. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/18178318/Activating_transcription_factor_3_up_regulated_by_c_Jun_NH_2__terminal_kinase/c_Jun_contributes_to_apoptosis_induced_by_potassium_deprivation_in_cerebellar_granule_neurons_ DB - PRIME DP - Unbound Medicine ER -