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Masato Tani

Publications and source records attributed to Masato Tani.

8 recordsLinked to original sources
PubMed2004

Functional characterization of single nucleotide polymorphisms with amino acid substitution in CYP1A2, CYP2A6, and CYP2B6 found in the Japanese population.

As a part of the studies conducted by the Pharma SNPs Consortium (PSC), the enzyme activities of CYP1A2, CYP2A6 and CYP2B6 variants with altered amino acids as a result of single nucleotide polymorphisms (SNPs) found among the Japanese population were analyzed under a unified protocol using the same lots of reagents by the laboratories participating in the PSC. Mutations in CYP1A2, CYP2A6 and CYP2B6 were introduced by site-directed mutagenesis and the wild type and mutated CYP molecules were expressed in Escherichia coli. The expressed cytochrome P450s were purified and the enzyme activities were measured in reconstitution systems. CYP1A2 and CYP1A2Gln478His did not show any differences in 7-ethoxyresorufin O-deethylase activity. CYP2A6 and CYP2A6Glu419Asp metabolized coumarin to form 7-hydroxycoumarin in a similar manner, whereas CYP2A6Ile471Thr showed low activity compared to the wild-type CYP2A6. CYP2B6, CYP2B6Pro167Ala and CYP2B6Arg487Cys showed the same activity for 7-ethoxy-4-triflouromethyl-coumarin O-deethylation. However, CYP2B6Gln172His was roughly twice as active as CYP2B6 and the other CYP2B6 variants for 7-ethoxy-4-triflouromethylcoumarin O-deethylation activity. Although higher inter- and intra-laboratory variations were observed for the calculated Km and V(max) values because the studies were conducted in several different laboratories, the degree of variations was reduced by the increased number of analyses and the adoption of a simple analysis system.

Amino Acid Substitution↗
PubMed2004

SF2809 compounds, novel chymase inhibitors from Dactylosporangium sp. 1. Taxonomy, fermentation, isolation and biological properties.

Six novel chymase inhibitors, SF2809-I, SF2809-II, SF2809-III, SF2809-IV, SF2809-V and SF2809-VI, were isolated from the fermentation broth of an actinomycete strain SF2809. The strain was identified as Dactylosporangium sp. by morphological, chemotaxonomical and phylogenetic studies. These six novel compounds inhibited recombinant human chymase in the range between IC50 of 0.014 and 7.3 microM. However, they showed little or no inhibitory activity against chymotrypsin or cathepsin G, even though these two and chymase belong to the chymotryptic serine protease family. This result indicates that these compounds work as specific chymase inhibitors.

Actinobacteria↗
PubMed2004

SF2809 compounds, novel chymase inhibitors from Dactylosporangium sp. 2. Structural elucidation.

Novel chymase inhibitors, SF2809-I, II, III, IV, V and VI, were isolated from the fermentation broth of Dactylosporangium sp. SF2809, and their structures were determined by spectroscopic analyses. SF2809 compounds commonly contain a substituted indole moiety and a quinolinone moiety. The two moieties are connected to a methylene carbon in SF2809-I and III. The other compounds, SF2809-II, IV, V and VI, have an additional moiety, a p-hydroxyphenyl group or a phenyl group. In these compounds, all of three moieties are connected to a methine carbon. Furthermore, studies concerning the stereochemistry of SF2809-V revealed that the isolated compound was racemic, and the isomer possessing (R)-configuration was about thirty times more potent than another isomer.

Chemical Phenomena↗
PubMed2004

[Death].

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Aged↗
PubMed2003

Preconditioning with heat shock further improved functional recovery in young adult but not in middle-aged rat hearts.

Ischemic preconditioning (PC) improves post-ischemic function, and heat shock (HS) mimics delayed PC in young animals. However, PC is not protective and the consequences of HS are not known in the aging hearts. This report examines the efficacy of HS and its synergy with PC in the middle-aged rat hearts. Hearts from 12- or 50-week-old rats were subjected to PC before 25 min ischemia followed by 30 min reperfusion 48 h after HS. HS induced HS proteins (HSP) in both age groups but that PC and HS translocated PKC-alpha and -delta only in young rats. The beneficial effects of HS and PC were additive and enhanced protein kinase C (PKC) translocation in young rats. However, neither HS alone nor in combination with PC conferred any functional advantage or accelerated PKC translocation in old rats. Similarly neither HS alone nor in combination with PC restore PC effects in old rats with impaired PKC activation, despite the induction of HSP, indicating that induction of HSP is insufficient for cytoprotection.

Aging↗
PubMed2002

COX-2-derived prostacyclin mediates opioid-induced late phase of preconditioning in isolated rat hearts.

Opioids confer biphasic (early and late) cardioprotection against myocardial infarction by opening mitochondrial ATP-sensitive K(+) channels. It is unknown whether cyclooxygenase-2 (COX-2), which mediates ischemia-induced late preconditioning, also mediates opioid-induced cardioprotection. Isolated perfused rat hearts were subjected to 20 min of global ischemia followed by 20 min of reperfusion. BW-373U86 (BW), a delta-opioid receptor agonist, was administered 1, 12, or 24 h before death. Recovery of left ventricular developed pressure (LVDP) after ischemia-reperfusion improved when BW was administered 1 or 24 h before ischemia (control: 57 +/- 8, BW 1 h: 75 +/- 5, BW 24 h: 85 +/- 6%) but not when it was administered 12 h before (60 +/- 5%). Levels of 6-keto-PGF(1alpha) (a stable metabolite of PGI(2)) in coronary effluent after 20 min of reperfusion were higher with 24-h BW pretreatment than in controls (1,053 +/- 92 vs. 724 +/- 81 pg/ml), whereas 6-keto-PGF(1alpha) levels at baseline did not differ. Administration of a selective COX-2 inhibitor, NS-398, abolished the late phase of cardioprotection (recovery of LVDP, 53 +/- 8%) and attenuated the increase in PGI(2) (706 +/- 138 pg/ml) but did not block the early phase of cardioprotection. The selective COX-1 inhibitor SC-560 did not affect either phase of protection. Western immunoblotting revealed upregulation of PGI(2) synthase protein 24 h after BW administration without changes in COX-1 and COX-2 protein levels. In conclusion, the late (but not the early) phase of delta-opioid receptor-induced preconditioning is mediated by COX-2. A functional coupling between COX-2 and upregulated PGI(2) synthase appears to underlie this cardioprotective phenomenon in the rat.

6-Ketoprostaglandin F1 alpha↗
PubMed2002

Aging abolishes the cardioprotective effect of combination heat shock and hypoxic preconditioning in reperfused rat hearts.

Hypoxic preconditioning (HP) does not improve post-ischemic function in the hearts of aging rats secondary to failure of protein kinase C (PKC) activation, but the effect of heat shock (HS) or preconditioning has not been studied. We studied whether HS increases tolerance to ischemia and whether its combination with HP would restore the cardioprotective effect in aging rat hearts. HS was performed in 12- and 50-week-old rats. Hearts were isolated and subjected to HP by 10 min hypoxic perfusion before 25 min ischemia followed by 30 min reperfusion 48 h after HS. Both HP and HS improved recovery of left ventricular function with translocation of PKC-delta from the cytosol to the nuclear fraction and induction of heat shock proteins, HSP27, HSP70, and alphaB-crystallin. The combination of HS and HP enhanced the translocation of PKC-delta in young rats, resulting in further improvement in functional recovery. In older rats, HP translocated PKC-delta from the membrane to the cytosol fraction, but did not improve functional recovery, although the combination of HS with HP induced HS proteins and translocated PKC-delta from the cytosol to the nuclear fraction. HS provided cardioprotection and had additive effects to HP with additional PKC-delta activation in young rats. However, in hearts from aging rats, HS alone was not cardioprotective, nor was its combination with HP, despite the induction of HS proteins and the activation of PKC-delta, resulting in its translocation to the nuclear fraction.

Aging↗