Characterization of human UGT2A3 expression using a prepared specific antibody against UGT2A3

UDP-Glucuronosyltransferase (UGT) 2A3 belongs to a UGT superfamily of phase II drug-metabolizing enzymes that catalyzes the glucuronidation of many endobiotics and xenobiotics. Previous studies have demonstrated that UGT2A3 is expressed in the human liver, small intestine, and kidney at the mRNA level; however, its protein expression has not been determined. Evaluation of the protein expression of UGT2A3 would be useful to determine its role at the tissue level. In this study, we prepared a specific antibody against human UGT2A3 and evaluated the relative expression of UGT2A3 in the human liver, small intestine, and kidney. Western blot analysis indicated that this antibody is specific to UGT2A3 because it did not cross-react with other human UGT isoforms or rodent UGTs. UGT2A3 expression in the human small intestine was higher than that in the liver and kidney. Via treatment with endoglycosidase, it was clearly demonstrated that UGT2A3 was N-glycosylated. UGT2A3 protein levels were significantly correlated with UGT2A3 mRNA levels in a panel of 28 human liver samples (r = 0.64, p <0.001). In conclusion, we successfully prepared a specific antibody against UGT2A3. This antibody would be useful to evaluate the physiological, pharmacological, and toxicological roles of UGT2A3 in human tissues. (C) 2019 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Evaluation of irradiation hardening of ion-irradiated V–4Cr–4Ti and V–4Cr–4Ti–0.15Y alloys by nanoindentation techniques

Irradiation hardening behavior of V–4Cr–4Ti and V–4Cr–4Ti–0.15Y alloys after Cu-ion beam irradiation were investigated with a combination between nanoindentation techniques and finite element method (FEM) analysis. The ion-irradiation experiments were conducted at 473 K with 2.4 MeV Cu2+ ions up to 7.6 dpa. For the unirradiated materials, the increase in nanoindentation hardness with decreasing indentation depth, so-called indentation size effect (ISE), was clearly observed. After irradiation, irradiation hardening in the measured depth was identified. Hardening behavior of bulk-equivalent hardness for V–4Cr–4Ti–0.15Y alloy was similar to that for V–4Cr–4Ti alloy. Y addition has little effect on irradiation hardening at 473 K. Adding the concept of geometrically necessary dislocations (GNDs) to constitutive equation of V–4Cr–4Ti alloy, the ISE was simulated. A constant value of α = 0.5 was derived as an optimal value to simulate nanoindentation test for ion-irradiated V–4Cr–4Ti alloy. Adding the term of irradiation hardening Δσirrad. to constitutive equation with α = 0.5, FEM analyses for irradiated surface of V–4Cr–4Ti alloy were carried out. The analytic data of FEM analyses based on neutron-irradiation hardening equivalent to 3.0 dpa agreed with the experimental data to 0.76 dpa. The comparison indicates that irradiation hardening by heavy ion-irradiation is larger than that by neutron-irradiation at the same displacement damage level. Possible mechanisms for extra hardening by heavy ion-irradiation are the processes that the injected Cu ions could effectively produce irradiation defects such as interstitials compared with neutrons, and that higher damage rate of ion-irradiation enhanced nucleation of irradiation defects and hence increased the number density of the defects compared with neutron-irradiation

Ubiquitylation of epsilon-COP by PIRH2 and regulation of the secretion of PSA

Ubiquitylation appears to be involved in the membrane trafficking system including endocytosis, exocytosis, and ER-to-Golgi transport. We found that PIRH2, which was identified as an interacting protein for androgen receptor or p53, interacts with and ubiquitylates the ε-subunit of coatmer complex, ε-COP. PIRH2 promotes the ubiquitylation of ε-COP in vitro and in vivo and consequently promotes the degradation of ε-COP. The interaction between PIRH2 and ε-COP is affected by the presence of androgen, and PIRH2 in the presence of androgen promotes ubiquitylation of ε-COP in vivo. Furthermore, overexpression of the wild type of PIRH2 in prostate cancer cells causes downregulation of the secretion of prostate-specific antigen (PSA), a secretory protein in prostate epithelial cells and one of diagnostic markers for prostate cancer. Our results indicate that PIRH2 functions as a regulator for COP I complex

The role of β (Al12Mg17) phase on corrosion behavior of the AM90 alloy in NaCl aqueous solution

The β phase (Al12Mg17) precipitated by heat treatment in some alloy compositions may result deterioration of corrosion resistance. However, much of its role remains unclear. The effect of the β phase on the corrosion resistance behavior in a NaCl solution was presented in this study. The specimen was Mg-9mass%Al (AM90) alloy and the content of the β phase precipitant was controlled systematically by aging time at 473 K. Area rate of β and lamellar phase in the specimens were 0, 10 and 100%, respectively. According to the results of cathodic polarization curves measurement, the corrosion current density of α phase was 0.215 A/m2 and β phase of it was 0.096 A/m2. While, the specimen includes 10% of β and lamellar phase showed large corrosion current density of 0.251 A/m2. Positive correlation between the β phase and the open circuit potential, suggest that the β phase acts as a cathodic electrode. Moreover, the microstructure after postentiostatic corrosion tests was also support the role of β phase