Post-transcriptional regulation of breast cancer resistance protein after intestinal ischemia-reperfusion.
Breast cancer resistance protein (BCRP), the product of the ABCG2 gene, is a recently identified ATP binding cassette half-transporter. BCRP is expressed in a variety of tumor cells and many normal human tissues. In the small intestine, BCRP can limit the influx and facilitate the efflux to prevent intracellular accumulation of BCRP substrates. Ischemia-reperfusion (I/R) induces the release of reactive oxygen species, and organs are severely damaged by I/R. It has been shown that the expression of transporters was altered in the organ after I/R. The present study was undertaken to clarify the expression of BCRP after intestinal I/R. We showed that the expression level of Bcrp was significantly decreased at 1 h after I/R. Bcrp mRNA level was not altered at 1 h after I/R. These results suggest that Bcrp expression was regulated by a post-transcriptional regulation mechanism after intestinal I/R. Bcrp mRNA level was increased at 24 h after I/R, and the expression level of Bcrp protein was of the same level or slightly increased compared with sham operated-rats. Bcrp was slightly located at the intestinal membrane at 24 h after intestinal I/R. These results suggested that Bcrp was not translocated to the intestinal membrane after intestinal I/R. There is little information on post-transcriptional regulation compared with information on transcriptional regulation. In this study, it was shown that Bcrp expression is regulated by post-transcriptional regulation after intestinal I/R. These results of this study may provide important information for further studies aimed at revealing the biological function of Bcrp.
Ogura
Jiro
J
Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo 060-0812, Japan.
Kobayashi
Masaki
M
Itagaki
Shirou
S
Hirano
Takeshi
T
Iseki
Ken
K
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis*; D000818:Animals; D015153:Blotting, Western; D019008:Drug Resistance, Neoplasm; D007082:Ileum / Q000098:blood supply / Q000378:metabolism; D007150:Immunohistochemistry; D007422:Intestines / Q000098:blood supply* / Q000503:physiopathology; D008297:Male; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000502:physiology; D015427:Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C489249:Abcg2 protein, rat