H uman ABCG2 (1-3) is a member of the ABC transporter gene family. The ABCG2 gene is located on chromosome 4q22, spans over 66 kb, and consists of 16 exons ranging from 60 to 532 bp. (4) The ABCG2 protein is a so-called 'half ABC transporter', existing as a homodimer linked through a cysteinyl disulfide bond at Cys603. (5-7) ABCG2 protein is expressed endogenously in placental trophoblast cells, the epithelium of the small intestine and liver canalicular membrane, as well as in ducts and lobules of the breast. Apical localization in the epithelium of the small intestine and colon indicates a possible role for human ABCG2 in regulating the uptake of orally ( p.o.) administered drugs as well as xenobiotics. (8) Overexpression of ABCG2 reportedly confers cancer cell resistance to anticancer drugs, such as topotecan, irinotecan (CPT-11) and mitoxantrone. (9)(10)(11)(12) In the case of drug resistance to irinotecan, SN-38-resistant PC-6/SN2-5H human lung carcinoma cells were shown to overexpress ABCG2 with reduced intracellular accumulation of SN-38, an active metabolite of CPT-11, and the SN-38-glucuronide conjugate. (12) Plasma membrane vesicles prepared from those cancer cells or ABCG2-transfected cells transported both SN-38 and SN-38-glucuronide ATP-dependently. (13,14) It has also been reported that ABCG2-transfected cells are resistant to photosensitizers, such as hematoporphyrin IX, pheophorbide a, and chlorine e6, suggesting a possible role for ABCG2 in cellular resistance to photodynamic therapy. (15) In this regard, we have most recently demonstrated that ABCG2 transports hematoporphyrin in an ATP-dependent manner. (16) SNP of ABCG2 have been suggested as a significant factor in a patient's response to medication and the risk of diseases. (17)(18)(19)(20)(21)(22) Sequencing of the ABCG2 gene from human samples has revealed over 80 different, naturally occurring sequence variations. (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) However, information is still limited regarding the functional impact of genetic polymorphisms of ABCG2. In addition, it was noticed that some discrepancies existed among reports in terms of the transport function and drug resistance profile of SNP variants of ABCG2. (25,28,30,31) The reason for such discrepancies is not known, but it may be due to differences in their experimental procedures.In the present study, we aimed to re-evaluate the impact of the genetic polymorphisms of ABCG2 on drug resistance by functionally validating its SNP in vitro. To analyze quantitatively the effect of non-synonymous SNP of ABCG2 on the protein expression level and the drug resistance profile, we used the Flp-In method to integrate one single copy of ABCG2 variant cDNA into FRTtagged genomic DNA. By using this method, we could exclude the random integration of ABCG2 cDNA into the chromosomal DNA of host cells. Furthermore, we have examined the pharmacological potency of our new camptothecin analogs (32,33) to determine whether they could circumvent ABCG2-associated drug resistance in human tumor cel...

The effect of ad libitum oral-administration of (-)catechin solution on ischemia-reperfusion-induced cell death of hippocampal CA1 in the gerbil was histologically examined. When (-)catechin solution instead of drinking water was orally administered ad libitum for 2 weeks, dose-dependent protection against neuronal death following by transient ischemia and reperfusion was observed. To evaluate the involvement of reduction of reactive-oxygen-species (ROIs) by the antioxidant activity of (-)catechin in this protection, the superoxide scavenging activity of the brain in catechin-treated gerbils was measured by ESR and spin-trapping using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). The superoxide scavenging activities of the brains obtained from catechin-treated gerbils were significantly higher than those of catechin-untreated animals. From these results, it was suggested that orally administered (-)catechin was absorbed, passed through the blood-brain barrier and that delayed neuronal death of hippocampal CA1 after ischemia-reperfusion was prevented due to its antioxidant activities.

Three kinds of alpha-glucosidases, I, II, and III, were purified from European honeybees, Apis mellifera L. In addition, an alpha-glucosidase was also purified from honey. Some properties, including the substrate specificity of honey alpha-glucosidase, were almost the same as those of alpha-glucosidase III. Specific antisera against the alpha-glucosidases were prepared to examine the localization of alpha-glucosidases in the organs of honeybees. It was immunologically confirmed for the first time that alpha-glucosidase I was present in ventriculus, and alpha-glucosidase II, in ventriculus and haemolymph. alpha-Glucosidase III, which became apparent to be honey alpha-glucosidase, was present in the hypopharyngeal gland, from which the enzyme may be secreted into nectar gathered by honeybees. Honey may be finally made up through the process whereby sucrose in nectar, in which glucose and fructose also are naturally contained, is hydrolyzed by secreted alpha-glucosidase III.

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