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Decreased mitochondrial DNA copy number in nerve cells and the hippocampus during nicotine exposure is mediated by autophagy
Wang, Hongjuan1; Chen, Huan1; Han, Shulei1; Fu, Yaning1; Tian, Yushan1; Liu, Yong2; Wang, An2; Hou, Hongwei1; Hu, Qingyuan1
2021-12-15
Source PublicationECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
ISSN0147-6513
Corresponding AuthorHou, Hongwei(houhw2015@163.com) ; Hu, Qingyuan(huqy@ztri.com.cn)
AbstractCigarette smoke is a harmful air pollutant and nicotine dependence is the essential cause of the tobacco epidemic. Since mitochondrial abnormalities are associated with substance addiction, in this work we used mitochondrial DNA (mtDNA) copy number as an indicator of mitochondrial function to investigate whether nicotine addicts also exhibit mitochondrial abnormalities. We found significantly lower mtDNA copy number in the peripheral blood of healthy nicotine addicts than in non-smokers, indicating that long-term nicotine exposure through smoking has detrimental effects on mitochondria. We also examined the effects of nicotine on mtDNA levels in a rat conditioned place preference (CPP) model of addiction and in cultured neuron cells, which revealed that the mtDNA copy number was significantly reduced in the hippocampus of CPP rats, in human neuroblastoma SHSY5Y cells, and in rat pheochromocytoma PC12 cells, suggesting that significantly reduced mtDNA copy number is a potential biomarker of nicotine addiction. In SH-SY5Y cells, nicotine treatment induced several mitochondrial defects, such as increased mtDNA damage, increased reactive oxygen species (ROS) levels, decreased mitochondrial membrane potential (o Psi m), and stimulation of autophagic flux via transcriptional up-regulation of several autophagy-related genes and elevated marker protein accumulation, although genes controlling mtDNA replication were unaffected. In addition, pretreatment with the autophagy inhibitor Bafilomycin A1 led to accumulation of microtubule-associated protein 1 light chain 3b-II (LC3B-II) and counteracted the nicotine induced decrease in mtDNA copy number. These results were recapitulated in PC12 cells, which also showed significant down-regulation of the marker SQSTM1/P62, suggesting that the decrease in mtDNA copy number is mediated by autophagy. This study shows that prolonged nicotine exposure, such as that in nicotine addicts, leads to a decrease of mtDNA copy number in neurons due to enhanced induction of autophagy. Capsule: It was found that smoking or nicotine exposure decreased mtDNA copy number based on population, animal, and cell models, and these effects appear to be mediated by autophagy.
Keywordnicotine mtDNA copy number autophagy mitochondrial abnormalities
DOI10.1016/j.ecoenv.2021.112831
WOS KeywordCONDITIONED PLACE PREFERENCE ; OXIDATIVE STRESS ; SYNAPTIC PLASTICITY ; CROSS-TALK ; EXPRESSION ; HOMEOSTASIS ; DYSFUNCTION ; MODULATION ; ADOLESCENT ; APOPTOSIS
Indexed BySCI
Language英语
Funding ProjectState Bureau Key Projects[110201402037] ; State Bureau Key Projects[110202001031 (JY-14)]
Funding OrganizationState Bureau Key Projects
WOS Research AreaEnvironmental Sciences & Ecology ; Toxicology
WOS SubjectEnvironmental Sciences ; Toxicology
WOS IDWOS:000704625900005
PublisherACADEMIC PRESS INC ELSEVIER SCIENCE
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Document Type期刊论文
Identifierhttp://ir.hfcas.ac.cn:8080/handle/334002/125498
Collection中国科学院合肥物质科学研究院
Corresponding AuthorHou, Hongwei; Hu, Qingyuan
Affiliation1.China Natl Tobacco Qual Supervis & Test Ctr, Zhengzhou, Peoples R China
2.Chinese Acad Sci, Hefei Inst Phys Sci, Hefei, Peoples R China
Recommended Citation
GB/T 7714
Wang, Hongjuan,Chen, Huan,Han, Shulei,et al. Decreased mitochondrial DNA copy number in nerve cells and the hippocampus during nicotine exposure is mediated by autophagy[J]. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY,2021,226.
APA Wang, Hongjuan.,Chen, Huan.,Han, Shulei.,Fu, Yaning.,Tian, Yushan.,...&Hu, Qingyuan.(2021).Decreased mitochondrial DNA copy number in nerve cells and the hippocampus during nicotine exposure is mediated by autophagy.ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY,226.
MLA Wang, Hongjuan,et al."Decreased mitochondrial DNA copy number in nerve cells and the hippocampus during nicotine exposure is mediated by autophagy".ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 226(2021).
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