The accumulation and efflux of lead partly depend on ATP-dependent efflux pump-multidrug resistance protein 1 and glutathione in testis Sertoli cells

详细信息    查看全文

• 作者：Shaoxin Huang^a ; ¹ ; Jingping Ye^a ; ^b ; ¹ ; Jun Yu^a ; Li Chen^a ; Langhuan Zhou^a ; Hong Wang^a ; Zhen Li^a ; Chunhong Wang^a ; ^c ; ^{wchunhong027@whu.edu.cn" class="auth_mail}
• 关键词：Pb ; lead ; TM4 ; mouse testis Sertoli cells ; Mrp1 ; multidrug resistance protein 1 ; TM4-sh ; Mrp1lower-expression TM4 cells ; ABC ; ATP-binding cassette ; GSH ; glutathione ; GST ; glutathione-S-transferase ; EA ; ethacrvnic acid ; BSO ; Lbuthionine&ndash ; sulfoximine ; RT-qPCR ; real-time fluorescence quantitative polymerase chain reaction ; MK571 ; (E)-3-[[[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl][[3-(dimethylamino)-3-oxopropyl]thio]methyl]thio]-propanoic acid ; PBS ; phosphate-buffered saline ; CCK8 ; Cell count
• 刊名：Toxicology Letters
• 出版年：2 May, 2014
• 年：2014
• 卷：226
• 期：3
• 页码：277-284
• 全文大小：1709 K

文摘

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 渭M for 12 h or 24 h, 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 9 h 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.