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: Dian-lei Wang, Chen-yin Wang, Yin Cao, Xian Zhang, Xiu-hua Tao, Li-li Yang, Jin-pei Chen, Shan-shan Wang, Ze-geng Li
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2014 Pg. 547379 ( 2014) ISSN: 1942-0994 [Electronic] United States
• PMID: 24672635 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Isothiocyanates
• Multidrug Resistance-Associated Proteins
• RNA, Messenger
• allyl isothiocyanate
• Acetylcysteine
• multidrug resistance-associated protein 1

Topics

• Acetylcysteine (pharmacology)
• Bronchi (cytology)
• Cell Line
• Cell Survival (drug effects)
• Epithelial Cells (cytology, drug effects, metabolism)
• Gene Expression Regulation (drug effects)
• Humans
• Isothiocyanates (pharmacology)
• Multidrug Resistance-Associated Proteins (genetics, metabolism)
• Protein Transport (drug effects)
• RNA, Messenger (genetics, metabolism)