title: The accumulation and efflux of lead partly depend on ATP-dependent efflux pump-multidrug resistance protein 1 and glutathione in testis Sertoli cells.
abstract: Since lead accumulation is toxic to cells, its excretion is crucial for organisms to survive the toxicity. In this study, mouse testis sertoli (TM4) and Mrp1 lower-expression TM4-sh cells were used to explore the lead accumulation characteristics, and the role of ATP-dependent efflux pump-multidrug resistance protein 1 (Mrp1) in lead excretion. TM4 cells possess Mrp-like transport activity. The expression levels of mrp1 mRNA and Mrp1 increased after lead treatments at first and then decreased. The maximum difference of relative mRNA expression reached 10 times. In the presence of lead acetate, the amount of cumulative lead in TM4-sh was much higher than that in TM4. After the treatment with lead acetate at 10-40 μM for 12h or 24h, the differences were about 2-8 times. After with the switch to lead-free medium, the cellular lead content in TM4-sh remains higher than that in TM4 cells at 1,3, 6, and 9h time points (P<0.01). Energy inhibitor sodium azide, Mrp inhibitors MK571 and glutathione (GSH) biosynthesis inhibitor BSO could block lead efflux from TM4 cells significantly. These results indicate that lead excretion may be mediated by Mrp1 and GSH in TM4 cells. Mrp1 could be one of the important intervention points for lead detoxification.
authors.affiliation: Department of Toxicology, School of Public Health, Wuhan University, Wuhan 430071, PR China.
authors.forename: Shaoxin
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Toxicology, School of Public Health, Wuhan University, Wuhan 430071, PR China; Renmin hospital of Wuhan University, Wuhan 430060, PR China.
authors.forename: Jingping
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Toxicology, School of Public Health, Wuhan University, Wuhan 430071, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Toxicology, School of Public Health, Wuhan University, Wuhan 430071, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Toxicology, School of Public Health, Wuhan University, Wuhan 430071, PR China.
authors.forename: Langhuan
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Toxicology, School of Public Health, Wuhan University, Wuhan 430071, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Toxicology, School of Public Health, Wuhan University, Wuhan 430071, PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Toxicology, School of Public Health, Wuhan University, Wuhan 430071, PR China; Global Health Institute, Wuhan University, Wuhan 430071, PR China. Electronic address: wchunhong027@whu.edu.cn.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D001692:Biological Transport; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000502:physiology*; D005982:Glutathione Transferase / Q000502:physiology; D007854:Lead / Q000493:pharmacokinetics* / Q000633:toxicity; D008297:Male; D051379:Mice; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism*
chemical_list: D005978:Glutathione; D005982:Glutathione Transferase; D007854:Lead; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; C421109:multidrug resistance-associated protein 1
keywords: GSH; Lead efflux; Lead exposure; Mrp1; TM4 cells