title: Allyl isothiocyanate increases MRP1 function and expression in a human bronchial epithelial cell line.
abstract: Multidrug resistance-associated protein 1 (MRP1), a member of the ATP-binding cassette (ABC) superfamily of transporters, plays an important role in normal lung physiology by protecting cells against oxidative stress and toxic xenobiotics. The present study investigates the effects of allyl isothiocyanate (AITC) on MRP1 mRNA and MRP1 protein expression and transporter activity in the immortalised human bronchial epithelial cell line 16HBE14o-. MRP1 mRNA and MRP1 protein expression in 16HBE14o- cells that were treated with allyl isothiocyanate were analysed by real-time PCR assay and Western blotting. The transport of carboxyfluorescein, a known MRP1 substrate, was measured by functional flow cytometry to evaluate MRP1 activity. Treatment with AITC at concentrations of 5-40 μM increased MRP1 protein levels in a concentration-dependent manner. AITC treatments at concentrations of 1-40 μM caused concentration-dependent increases in MRP1 mRNA levels that were up to seven times greater than the levels found in control cells. Finally, AITC treatment at concentrations of 5-40 μM significantly increased MRP1-dependent efflux in 16HBE14o- cells. These results suggest that AITC can increase the expression and activity of MRP1 in 16HBE14o- cells in a concentration-dependent manner. The upregulation of MRP1 activity and expression by AITC could produce therapeutic effects in the treatment of lung disease.
authors.affiliation: Anhui University of Chinese Medicine, Hefei, Anhui 230038, China.
authors.forename: Dian-lei
authors.initials: DL
authors.lastname: Wang
authors.affiliation: Anhui University of Chinese Medicine, Hefei, Anhui 230038, China.
authors.forename: Chen-yin
authors.initials: CY
authors.lastname: Wang
authors.affiliation: The Fourth People's Hospital of Hefei, Hefei, Anhui 230022, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Anhui University of Chinese Medicine, Hefei, Anhui 230038, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Anhui University of Chinese Medicine, Hefei, Anhui 230038, China.
authors.forename: Xiu-hua
authors.initials: XH
authors.lastname: Tao
authors.affiliation: Anhui University of Chinese Medicine, Hefei, Anhui 230038, China.
authors.forename: Li-li
authors.initials: LL
authors.lastname: Yang
authors.affiliation: Anhui University of Chinese Medicine, Hefei, Anhui 230038, China.
authors.forename: Jin-pei
authors.initials: JP
authors.lastname: Chen
authors.affiliation: Anhui University of Chinese Medicine, Hefei, Anhui 230038, China.
authors.forename: Shan-shan
authors.initials: SS
authors.lastname: Wang
authors.affiliation: Anhui University of Chinese Medicine, Hefei, Anhui 230038, China ; The First Hospital Affiliated to Anhui University of Chinese Medicine, Hefei, Anhui 230031, China.
authors.forename: Ze-geng
authors.initials: ZG
authors.lastname: Li
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D000111:Acetylcysteine; D017879:Isothiocyanates; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; C004471:allyl isothiocyanate; C421109:multidrug resistance-associated protein 1