title: Secreted miR-34a in astrocytic shedding vesicles enhanced the vulnerability of dopaminergic neurons to neurotoxins by targeting Bcl-2.
abstract: MicroRNAs (miRNAs) are a class of noncoding RNAs that regulates target gene expression at posttranscriptional level, leading to further biological functions. We have demonstrated that microvesicles (MVs) can deliver miRNAs into target cells as a novel way of intercellular communication. It is reported that in central nervous system, glial cells release MVs, which modulate neuronal function in normal condition. To elucidate the potential role of glial MVs in disease, we evaluated the effects of secreted astrocytic MVs on stress condition. Our results demonstrated that after Lipopolysaccharide (LPS) stimulation, astrocytes released shedding vesicles (SVs) that enhanced vulnerability of dopaminergic neurons to neurotoxin. Further investigation showed that increased astrocytic miR-34a in SVs was involved in this progress via targeting anti-apoptotic protein Bcl-2 in dopaminergic neurons. We also found that inhibition of astrocytic miR-34a after LPS stimulation can postpone dopaminergic neuron loss under neurotoxin stress. These data revealed a novel mechanism underlying astrocyte-neuron interaction in disease.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences (NAILS), Nanjing University School of Life Sciences, Nanjing, 210093 China.|Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, Nanjing, 210093 China.
authors.forename: Susu
authors.initials: S
authors.lastname: Mao
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences (NAILS), Nanjing University School of Life Sciences, Nanjing, 210093 China.|Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, Nanjing, 210093 China.|Center of Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, Nanjing, 210003 China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences (NAILS), Nanjing University School of Life Sciences, Nanjing, 210093 China.|Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, Nanjing, 210093 China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences (NAILS), Nanjing University School of Life Sciences, Nanjing, 210093 China.|Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, Nanjing, 210093 China.
authors.forename: Chenyu
authors.initials: C
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences (NAILS), Nanjing University School of Life Sciences, Nanjing, 210093 China.|Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, Nanjing, 210093 China.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology*; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D035683:MicroRNAs / Q000378:metabolism*; D009498:Neurotoxins / Q000633:toxicity*; D016627:Oxidopamine; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D013312:Stress, Physiological / Q000187:drug effects
chemical_list: D008070:Lipopolysaccharides; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D009498:Neurotoxins; D019253:Proto-Oncogene Proteins c-bcl-2; D016627:Oxidopamine