Repeated electroconvulsive seizure induces c-Myc down-regulation and Bad inactivation in the rat frontal cortex.
10.3858/emm.2008.40.4.435
- Author:
Won Je JEON
1
;
Se Hyun KIM
;
Myoung Suk SEO
;
Yeni KIM
;
Ung Gu KANG
;
Yong Sung JUHNN
;
Yong Sik KIM
Author Information
1. Clinical Research Institute, Seoul National University Hospital, Seoul, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
apoptosis;
bcl-2-associated X protein;
electroconvulsive therapy;
nerve growth factors;
proto-oncogene proteins c-bcl-2;
proto-oncogene proteins c-myc;
ubiquitination
- MeSH:
14-3-3 Proteins/metabolism;
Animals;
Down-Regulation;
Electroconvulsive Therapy/*adverse effects;
Frontal Lobe/*metabolism;
Male;
Models, Biological;
Neurons/metabolism;
Periodicity;
Phosphorylation;
Protein Binding;
Protein Processing, Post-Translational;
Proto-Oncogene Proteins c-bcl-2/metabolism;
Proto-Oncogene Proteins c-myc/*metabolism;
Rats;
Rats, Sprague-Dawley;
Seizures/etiology/*metabolism;
Tumor Cells, Cultured;
Ubiquitination;
bcl-Associated Death Protein/antagonists & inhibitors/*metabolism
- From:Experimental & Molecular Medicine
2008;40(4):435-444
- CountryRepublic of Korea
- Language:English
-
Abstract:
Repeated electroconvulsive seizure (ECS), a model for electroconvulsive therapy (ECT), exerts neuroprotective and proliferative effects in the brain. This trophic action of ECS requires inhibition of apoptotic activity, in addition to activation of survival signals. c-Myc plays an important role in apoptosis of neurons, in cooperation with the Bcl-2 family proteins, and its activity and stability are regulated by phosphorylation and ubiquitination. We examined c-Myc and related proteins responsible for apoptosis after repeated ECS. In the rat frontal cortex, repeated ECS for 10 days reduced the total amount of c-Myc, while increasing phosphorylation of c-Myc at Thr58, which reportedly induces degradation of c-Myc. As expected, ubiquitination of both phosphorylated and total c-Myc increased after 10 days ECS, suggesting that ECS may reduce c-Myc protein level via ubiquitination-proteasomal degradation. Bcl-2 family proteins, caspase, and poly(ADP-ribose) polymerase (PARP) were investigated to determine the consequence of down-regulating c-Myc. Protein levels of Bcl-2, Bcl-X(L), Bax, and Bad showed no change, and cleavage of caspase-3 and PARP were not induced. However, phosphorylation of Bad at Ser-155 and binding of Bad to 14-3-3 increased without binding to Bcl-X(L) after repeated ECS, implying that repeated ECS sequesters apoptotic Bad and frees pro-survival Bcl-X(L). Taken together, c-Myc down-regulation via ubiquitination-proteasomal degradation and Bad inactivation by binding to 14-3-3 may be anti-apoptotic mechanisms elicited by repeated ECS in the rat frontal cortex. This finding further supports the trophic effect of ECS blocking apoptosis as a possible therapeutic effect of ECT.
