Poly(ADP-ribose) polymerase inhibitor is neuroprotective in epileptic rat via apoptosis-inducing factor and Akt signaling.
3-Aminobenzamide (3-AB), an inhibitor of poly(ADP-ribose) polymerase (PARP), has been proved to have neuroprotective properties. In this study, we examined the role of 3-AB in rat hippocampal neuron death induced by seizures. Our data showed that the seizures resulted in PARP activation and translocation of the apoptosis-inducing factor from the mitochondria to the nucleus, leading to neuron death. These effects could, however, all be abolished by 3-AB. Moreover, we showed that 3-AB facilitated Akt activation and decreased the activity of its downstream target, glycogen synthase kinase-3beta. Altogether, our data suggested that 3-AB might have a therapeutic value in seizure-induced hippocampal neuron damage, probably due to the inhibition of apoptosis and activation of Akt cell survival signaling.
Wang
Sheng-jun
SJ
Department of Neurology, Qilu Hospital of Shandong University, China.
Wang
Shu-hua
SH
Song
Zhao-feng
ZF
Liu
Xue-wu
XW
Wang
Rong
R
Chi
Zhao-fu
ZF
D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D051033:Apoptosis Inducing Factor / Q000187:drug effects* / Q000378:metabolism; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D038362:Glycogen Synthase Kinase 3 / Q000187:drug effects / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D051033:Apoptosis Inducing Factor; D001549:Benzamides; D018696:Neuroprotective Agents; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C025160:3-aminobenzamide; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3