title: Mir143-BBC3 cascade reduces microglial survival via interplay between apoptosis and autophagy: Implications for methamphetamine-mediated neurotoxicity.
abstract: BBC3 (BCL2 binding component 3) is a known apoptosis inducer; however, its role in microglial survival remains poorly understood. In addition to the classical transcription factor TRP53, Mir143 is involved in BBC3 expression at the post-transcriptional level. Here, we identify unique roles of Mir143-BBC3 in mediating microglial survival via the regulation of the interplay between apoptosis and autophagy. Autophagy inhibition accelerated methamphetamine-induced apoptosis, whereas autophagy induction attenuated the decrease in microglial survival. Moreover, anti-Mir143-dependent BBC3 upregulation reversed the methamphetamine-induced decrease in microglial survival via the regulation of apoptosis and autophagy. The in vivo relevance of these findings was confirmed in mouse models, which demonstrated that the microinjection of anti-Mir143 into the hippocampus ameliorated the methamphetamine-induced decrease in microglia as well as that observed in heterozygous Mir143(+/-) mice. These findings provide new insight regarding the specific contributions of Mir143-BBC3 to microglial survival in the context of drug abuse.
authors.affiliation: a Department of Pharmacology , School of Medicine, Southeast University , Nanjing , Jiangsu , China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: a Department of Pharmacology , School of Medicine, Southeast University , Nanjing , Jiangsu , China.
authors.forename: Kai
authors.initials: K
authors.lastname: Shen
authors.affiliation: a Department of Pharmacology , School of Medicine, Southeast University , Nanjing , Jiangsu , China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Bai
authors.affiliation: a Department of Pharmacology , School of Medicine, Southeast University , Nanjing , Jiangsu , China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Lv
authors.affiliation: a Department of Pharmacology , School of Medicine, Southeast University , Nanjing , Jiangsu , China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Huang
authors.affiliation: a Department of Pharmacology , School of Medicine, Southeast University , Nanjing , Jiangsu , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: b Department of Physiology , School of Medicine, Southeast University , Nanjing , Jiangsu , China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chao
authors.affiliation: c Department of Biochemistry and Molecular Biology , School of Biomedical Sciences, Monash University , Melbourne , Victoria Australia.|d Biomedicine Discovery Institute, Monash University , Melbourne , Victoria Australia.
authors.forename: Lan K
authors.initials: LK
authors.lastname: Nguyen
authors.affiliation: e Jiangsu Key Laboratory of Neurodegeneration , Department of Pharmacology , Nanjing Medical University , Nanjing , Jiangsu , China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hua
authors.affiliation: f School of Medicine , Southeast University , Nanjing , Jiangsu , China.
authors.forename: Guangming
authors.initials: G
authors.lastname: Gan
authors.affiliation: e Jiangsu Key Laboratory of Neurodegeneration , Department of Pharmacology , Nanjing Medical University , Nanjing , Jiangsu , China.
authors.forename: Gang
authors.initials: G
authors.lastname: Hu
authors.affiliation: a Department of Pharmacology , School of Medicine, Southeast University , Nanjing , Jiangsu , China.|g Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University , Nanjing , Jiangsu , China.
authors.forename: Honghong
authors.initials: H
authors.lastname: Yao
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy; D002470:Cell Survival; D004195:Disease Models, Animal; D006579:Heterozygote; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; C542359:MIRN143 microRNA, human; D035683:MicroRNAs; C532884:MIRN143 microRNA, mouse; C488588:PUMA protein, mouse; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; D008694:Methamphetamine
keywords: BBC3; Mir143; apoptosis; autophagy; methamphetamine; microglia