Formation of a stable, lattice-framework disilene: a strategy for the construction of bulky substituents.
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Journal Article↗
Biomedical subjects
Shigeki Matsumoto
Publications and source records attributed to Shigeki Matsumoto.
Explosive dark matter annihilation.
In this Letter we study pair annihilation processes of dark matter (DM) in the Universe, in the case that the DM is an electroweak gauge nonsinglet. In the current Universe, in which the DM is highly nonrelativistic, the nonperturbative effect may enhance the DM annihilation cross sections, especially for that to two photons, by several orders of magnitude. We also discuss sensitivities in future searches for anomalous gamma rays from the galactic center, which originate from DM annihilation.
Journal Article↗
Functional characterization of active transport of progesterone to adrenal cells.
The characterization of the transport mechanism of progesterone, which is one of the neutral steroids in the adrenal cells, has been studied by the examination of progesterone uptake into the monolayers of SW-13 cells (a human adrenal adenocarcinoma cell line). The uptake of [(3)H]progesterone at a tracer concentration (1 nM) exhibited temperature, pH and sodium dependency. According to kinetic analysis of the concentration dependence, the uptake of progesterone involves saturable and non-saturable processes. The uptake for the saturable process, which gave K(t) values (half-saturation concentration) of 4.7 +/- 8.7 microM, was inhibited by metabolic inhibitors and amino-acid modifiers but not by endocytosis inhibitors or substrates for known transporters. The uptake of progesterone was also inhibited by several neutral steroids but not by anionic steroids. The inhibition by both beta-estradiol and estriol was competitive. The uptake of progesterone by the adrenal cells might be at least partially accounted for by a specific carrier-mediated transport mechanism generated by sodium ions and an electrochemical mechanism.
Adenocarcinoma↗
Interaction between the N-terminal and middle regions is essential for the in vivo function of HSP90 molecular chaperone.
At the primary structure level, the 90-kDa heat shock protein (HSP90) is composed of three regions: the N-terminal (Met(1)-Arg(400)), middle (Glu(401)-Lys(615)), and C-terminal (Asp(621)-Asp(732)) regions. In the present study, we investigated potential subregion structures of these three regions and their roles. Limited proteolysis revealed that the N-terminal region could be split into two fragments carrying residues Met(1) to Lys(281) (or Lys(283)) and Glu(282) (or Tyr(284)) to Arg(400). The former is known to carry the ATP-binding domain. The fragments carrying the N-terminal two-thirds (Glu(401)-Lys(546)) and C-terminal one-third of the middle region were sufficient for the interactions with the N- and C-terminal regions, respectively. Yeast HSC82 that carried point mutations in the middle region causing deficient binding to the N-terminal region could not support the growth of HSP82-depleted cells at an elevated temperature. Taken together, our data show that the N-terminal and middle regions of the HSP90 family protein are structurally divided into two respective subregions. Moreover, the interaction between the N-terminal and middle regions is essential for the in vivo function of HSP90 in yeast.
Amino Acid Sequence↗
Involvement of CYP2J2 on the intestinal first-pass metabolism of antihistamine drug, astemizole.
Orally administered astemizole is well absorbed but undergoes an extensive first-pass metabolism to O-desmethylastemizole. Desmethylastemizole is formed in the human microsomal systems of the small intestine as well as the liver, which suggests the role of cytochromes P450 (P450s) in the first-pass metabolism of astemizole. Human P450s involved in the O-demethylation of astemizole have, however, not been identified, and the involvement of twelve known drug-metabolizing P450s were denied. During the course of the P450 identification study, higher activities of the astemizole O-demethylation in the rabbit small intestine than in the liver (about 3-fold) were found. These data suggest the possible involvement of CYP2J, since P450 included in this subfamily is dominantly expressed in the small intestine of rabbits. Therefore, CYP2J2 cDNA has been isolated from the human cDNA library and expressed in COS-1 cells. A clear activity of astemizole O-demethylation was detected in recombinant CYP2J2 with K(m) = 0.65 microM and V(max) = 1129 pmol/nmol P450/min. Expression of the immunoreactive protein with CYP2J2 antibody was detected in the small intestine and liver. Expression levels of the immunoreactive protein with the CYP2J2 antibody in the small intestine were well correlated with the activities of the astemizole O-demethylation (r = 0.901, n = 5, p < 0.05). The CYP2J2 substrates, arachidonic acid and ebastine, strongly inhibited the microsomal astemizole O-demethylation in the human small intestines and recombinant CYP2J2. These results indicate the involvement of CYP2J2 in the presystemic elimination of astemizole in the human small intestine.
Animals↗
Studies on the metabolic fate of M17055, a novel diuretic (4): species difference in metabolic pathway and identification of human CYP isoform responsible for the metabolism of M17055.
The metabolic profile of M17055, a novel diuretic, after administration to experimental animals and after incubation with human liver microsomes was investigated. 1. Extensive metabolism was observed in rats and monkeys and the structures of six metabolites (RU1, RU2, and RU3 from rat urine or liver perfusate; MU1, MU2 and MU3 from monkey urine) were assumed or identified. The clear species difference of metabolism was revealed between rats and a monkey with different structures of the isolated metabolites. 2. When these metabolites were quantified using radioactive material, RU3, RU1 and MU3 were considered to be major metabolites in rat urine, rat bile and monkey urine respectively, while in a dog, unchanged drug was observed as the major component indicating only little metabolism occurred in dog, when administered intravenously. 3. RU1 and RU2 were also generated from [(14)C]M17055 after incubation with human liver microsomes, suggesting that the metabolic pathway of M17055 in humans involves that observed in rats. 4. [(14)C]M17055 metabolism in human liver microsomes was inhibited by CYP2C8/9 and CYP3A4/5 inhibitors, and also by the antibodies that recognize CYP2C8/9/19 and CYP3A4. Significant correlations were observed between the rate of [(14)C]M17055 metabolism and the activity of testosterone 6beta-hydroxylation or tolbutamide methyl-hydroxylation. cDNA-expressed CYP3A4 and CYP2C9 could catalyze the metabolism of [(14)C]M17055. These results suggest that the metabolism of M17055 in human liver microsomes is catalyzed mainly by CYP3A4 and CYP2C9.
Journal Article↗