|
KMID : 0620920080400040435
|
|
Experimental & Molecular Medicine
2008 Volume.40 No. 4 p.435 ~ p.444
|
|
|
Repeated electroconvulsive seizure induces c-Myc down-regulation and Bad inactivation in the rat frontal cortex
|
|
Jeon Won-Je
Kim Yong-Sik
Kang Ung-Gu
Seo Moung-Seock
Kim Se-Hyun
Juhnn Yong-Sung
Kim Ye-Ni
|
|
|
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-XL, 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-XL after repeated ECS, implying that repeated ECS sequesters apoptotic Bad and frees pro-survival Bcl-XL. 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.
|
|
|
KEYWORD
|
|
|
apoptosis, bcl-2-associated X protein, electroconvulsive therapy, nerve growth factors, proto-oncogene proteins c-bcl-2, proto-oncogene proteins c-myc, ubiquitination
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
    
|
|