Repeated electroconvulsive seizure induces c-Myc down-regulation and Bad inactivation in the rat frontal cortex

Won Je Jeon, Se Hyun Kim, Myoung Suk Seo, Yeni Kim, Ung Gu Kang, Yong Sung Juhnn, Yong Sik Kim

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)435-444
Number of pages10
JournalExperimental and Molecular Medicine
Volume40
Issue number4
DOIs
StatePublished - 31 Aug 2008

Keywords

  • Apoptosis
  • Bcl-2-associated X protein
  • Electroconvulsive therapy
  • Nerve growth factors
  • Pro-to-oncogene proteins c-bcl-2
  • Proto-oncogene proteins c-myc
  • Ubiquitination

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