title: Heroin activates ATF3 and CytC via c-Jun N-terminal kinase pathways to mediate neuronal apoptosis.
abstract: BACKGROUND Drug abuse and addiction has become a major public health problem that impacts all societies. The use of heroin may cause spongiform leukoencephalopathy (SLE). MATERIAL AND METHODS Cerebellar granule cells were derived from 7-day-old Sprague-Dawley rat pups. Neurons were dissociated from freshly dissected cerebella by mechanical disruption in the presence of 0.125% trypsin and DNaseI and then seeded at a density of 4×10^6 cells/ml in Dulbecco's modified Eagle's medium/nutrient mixture F-12 ham's containing 10% fetal bovine serum and Arc-C(sigma) at concentrations to inhibit glial cell growth inoculated into 6-well plates and a small dish. RESULTS We found that heroin induces the apoptosis of primary cultured cerebellar granule cells (CGCS) and that the c-Jun N-terminal kinase (JNK) pathway was activated under heroin treatment and stimulated obvious increases in the levels of C-jun, Cytc, and ATF3mRNA. CYTC and ATF3 were identified as candidate targets of the JNK/c-Jun pathway in this process because the specificity inhibitors SP600125 of JNK/C-jun pathways reduced the levels of C-jun, Cytc, and ATF3mRNA. The results suggested that SP600125 of JNK/C-jun can inhibit heroin-induced apoptosis of neurons. CONCLUSIONS The present study analyzes our understanding of the critical role of the JNK pathway in the process of neuronal apoptosis induced by heroin, and suggests a new and effective strategy to treat SLE.
authors.affiliation: Department of Science and Research Education Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Sinciang, China (mainland).
authors.forename: Hongwei
authors.initials: H
authors.lastname: Pu
authors.affiliation: Xinjiang Key Laboratory of Medical Animal Model Research, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Sinciang, China (mainland).
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
authors.affiliation: College of Basic Medicine, Xinjiang Medical University, Urumqi, Sinciang, China (mainland).
authors.forename: Liping
authors.initials: L
authors.lastname: Su
authors.affiliation: Department of Micro-Reconstructive Surgery of Orthopedics Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Sinciang, China (mainland).
authors.forename: Chuang
authors.initials: C
authors.lastname: Ma
authors.affiliation: College of International Education, Xinjiang Medical University, Urumqi, Sinciang, China (mainland).
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Basic Medicine, Xinjiang Medical University, Urumqi, Sinciang, China (mainland).
authors.forename: Liping
authors.initials: L
authors.lastname: Zhang
authors.affiliation: College of Basic Medicine, Xinjiang Medical University, Urumqi, Sinciang, China (mainland).
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.affiliation: Xinjiang Key Laboratory of Medical Animal Model Research, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Sinciang, China (mainland).
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Li
authors.affiliation: College of Basic Medicine, Xinjiang Medical University, Urumqi, Sinciang, China (mainland).
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Forensic Science, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China (mainland).
authors.forename: Xiaoshan
authors.initials: X
authors.lastname: Liu
authors.affiliation: College of Basic Medicine, Xinjiang Medical University, Urumqi, Sinciang, China (mainland).
authors.forename: Jianlong
authors.initials: J
authors.lastname: Zhang
mesh_terms: D051700:Activating Transcription Factor 3 / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045304:Cytochromes c / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D005455:Fluorescent Antibody Technique; D003932:Heroin / Q000494:pharmacology*; D066298:In Vitro Techniques; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D051700:Activating Transcription Factor 3; C497108:Atf3 protein, rat; D017931:DNA Primers; D003932:Heroin; D045304:Cytochromes c; D048031:JNK Mitogen-Activated Protein Kinases
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