TY - JOUR
T1 - Repeated electroconvulsive seizure induces c-Myc down-regulation and Bad inactivation in the rat frontal cortex
AU - Jeon, Won Je
AU - Kim, Se Hyun
AU - Seo, Myoung Suk
AU - Kim, Yeni
AU - Kang, Ung Gu
AU - Juhnn, Yong Sung
AU - Kim, Yong Sik
PY - 2008/8/31
Y1 - 2008/8/31
N2 - Repeated electroconvulsive seizure (ECS), a model for electroconvulsive therapy (ECT), exerts neuro-protective 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, BcI-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 BcI-X l 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.
AB - Repeated electroconvulsive seizure (ECS), a model for electroconvulsive therapy (ECT), exerts neuro-protective 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, BcI-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 BcI-X l 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.
KW - Apoptosis
KW - Bcl-2-associated X protein
KW - Electroconvulsive therapy
KW - Nerve growth factors
KW - Pro-to-oncogene proteins c-bcl-2
KW - Proto-oncogene proteins c-myc
KW - Ubiquitination
UR - http://www.scopus.com/inward/record.url?scp=51949104604&partnerID=8YFLogxK
U2 - 10.3858/emm.2008.40.4.435
DO - 10.3858/emm.2008.40.4.435
M3 - Article
C2 - 18779656
AN - SCOPUS:51949104604
SN - 1226-3613
VL - 40
SP - 435
EP - 444
JO - Experimental and Molecular Medicine
JF - Experimental and Molecular Medicine
IS - 4
ER -