Repeated electroconvulsive seizure induces c-Myc down-regulation and Bad inactivation in the rat frontal cortex.
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-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.
Mesh Terms:
14-3-3 Proteins, Animals, Down-Regulation, Electroconvulsive Therapy, Frontal Lobe, Male, Models, Biological, Neurons, Periodicity, Phosphorylation, Protein Binding, Protein Processing, Post-Translational, Proto-Oncogene Proteins c-bcl-2, Proto-Oncogene Proteins c-myc, Rats, Rats, Sprague-Dawley, Seizures, Tumor Cells, Cultured, Ubiquitination, bcl-Associated Death Protein
14-3-3 Proteins, Animals, Down-Regulation, Electroconvulsive Therapy, Frontal Lobe, Male, Models, Biological, Neurons, Periodicity, Phosphorylation, Protein Binding, Protein Processing, Post-Translational, Proto-Oncogene Proteins c-bcl-2, Proto-Oncogene Proteins c-myc, Rats, Rats, Sprague-Dawley, Seizures, Tumor Cells, Cultured, Ubiquitination, bcl-Associated Death Protein
Exp. Mol. Med.
Date: Aug. 31, 2008
PubMed ID: 18779656
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