Decreased mitochondrial DNA copy number in nerve cells and the hippocampus during nicotine exposure is mediated by autophagy

doi:10.1016/j.ecoenv.2021.112831

	Decreased mitochondrial DNA copy number in nerve cells and the hippocampus during nicotine exposure is mediated by autophagy
	Wang, Hongjuan 1; Chen, Huan 1; Han, Shulei 1; Fu, Yaning 1; Tian, Yushan 1; Liu, Yong 2; Wang, An 2; Hou, Hongwei 1; Hu, Qingyuan 1
刊名	ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
	2021-12-15
卷号	226
关键词	nicotine mtDNA copy number autophagy mitochondrial abnormalities
ISSN号	0147-6513
DOI	10.1016/j.ecoenv.2021.112831
通讯作者	Hou, Hongwei(houhw2015@163.com) ; Hu, Qingyuan(huqy@ztri.com.cn)
英文摘要	Cigarette 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.
资助项目	State Bureau Key Projects[110201402037] ; State Bureau Key Projects[110202001031 (JY-14)]
WOS关键词	CONDITIONED PLACE PREFERENCE ; OXIDATIVE STRESS ; SYNAPTIC PLASTICITY ; CROSS-TALK ; EXPRESSION ; HOMEOSTASIS ; DYSFUNCTION ; MODULATION ; ADOLESCENT ; APOPTOSIS
WOS研究方向	Environmental Sciences & Ecology ; Toxicology
语种	英语
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS记录号	WOS:000704625900005
资助机构	State Bureau Key Projects
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/125497]
专题	中国科学院合肥物质科学研究院
通讯作者	Hou, Hongwei; Hu, Qingyuan
作者单位	1.China Natl Tobacco Qual Supervis & Test Ctr, Zhengzhou, Peoples R China 2.Chinese Acad Sci, Hefei Inst Phys Sci, Hefei, Peoples R China
推荐引用方式 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).