title: Suppression of ZIP8 expression is a common feature of cadmium-resistant and manganese-resistant RBL-2H3 cells.
abstract: Rat basophilic leukemia RBL-2H3 cells show markedly high sensitivity to both CdCl2 and MnCl2 compared with other rat cell lines, due to efficient accumulation of cadmium and manganese. To clarify the roles of metal transporters in hyperaccumulation of cadmium and manganese in RBL-2H3 cells, Cd-resistant and Mn-resistant cells were developed from RBL-2H3 cells by continuous exposure to CdCl2 and MnCl2, respectively. The established Cd-resistant (RBL-Cdr) and Mn-resistant (RBL-Mnr) cells exhibited about 20 times higher LC50 values of CdCl2 and MnCl2, respectively, than parental RBL-2H3 cells, and showed cross-resistance to each metal. The resistance to cadmium and manganese was primarily conferred by a marked decrease in the uptake of both metals. RBL-Cdr cells also showed cross-resistance to HgCl2 and AgNO3 probably due to enhanced expression of metallothionein. Among the possible transporters involved in the uptake of Cd(2+) and Mn(2+), the expression of ZIP8 (Zrt-, Irt-related protein 8), encoded by Slc39a8, showed a marked suppression in both RBL-Cdr and RBL-Mnr cells. These results suggest that ZIP8 plays a pivotal role in the transport and toxicity of Cd(2+) and Mn(2+) in RBL-2H3 cells.
authors.affiliation: Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Fujishiro
authors.forename: Toshinao
authors.initials: T
authors.lastname: Ohashi
authors.forename: Miki
authors.initials: M
authors.lastname: Takuma
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Himeno
mesh_terms: D000818:Animals; D002104:Cadmium / Q000378:metabolism / Q000633:toxicity*; D019256:Cadmium Chloride / Q000633:toxicity; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002712:Chlorides / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects; D008345:Manganese / Q000378:metabolism / Q000633:toxicity*; D017895:Manganese Compounds; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
chemical_list: D027682:Cation Transport Proteins; D002712:Chlorides; D017895:Manganese Compounds; D012333:RNA, Messenger; C561850:Slc39a8 protein, rat; D002104:Cadmium; D008345:Manganese; D008668:Metallothionein; D019256:Cadmium Chloride; C025340:manganese chloride