title: Activation of caspase-3 and c-Jun NH2-terminal kinase signaling pathways involving heroin-induced neuronal apoptosis.
abstract: Heroin has been shown to cause spongiform leukoencephalopathy (SLE) in heroin addicts. In this study, we found that heroin could induce apoptosis of primary cultured cerebellar granule cells (CGC) and c-Jun N-terminal kinase (JNK) pathway is activated during CGCs apoptosis. Inhibiting JNK with a specific inhibitor, SP600125, reduced the levels of c-Jun phosphorylation and caspase-3 activation. We also showed that use the JNK inhibitor SP600125, caspase inhibitor z-VAD, or use SP600125 and z-VAD together significantly suppressed cell death induced by heroin. These results indicate that JNK pathway is an important mediator of the neurotoxic effects of heroin and inhibiting JNK activity may represent a new and effective strategy to treat heroin-induced SLE.
authors.affiliation: Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Bingquan
authors.initials: B
authors.lastname: Lai
authors.forename: Hongwei
authors.initials: H
authors.lastname: Pu
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Cao
authors.forename: Hualan
authors.initials: H
authors.lastname: Jing
authors.forename: Xiaoshan
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism* / Q000502:physiology; D061945:Caspase Inhibitors; D002531:Cerebellum / Q000201:enzymology / Q000473:pathology; D003594:Cytoplasmic Granules / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D003932:Heroin / Q000633:toxicity*; D006556:Heroin Dependence / Q000201:enzymology* / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D048055:Mitogen-Activated Protein Kinase 8 / Q000037:antagonists & inhibitors / Q000502:physiology*; D009294:Narcotics / Q000633:toxicity; D009474:Neurons / Q000201:enzymology* / Q000473:pathology; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D061945:Caspase Inhibitors; D009294:Narcotics; D003932:Heroin; D048055:Mitogen-Activated Protein Kinase 8; C505410:Casp3 protein, rat; D053148:Caspase 3