138 research outputs found

    Characterization of genetically modified mice for phosphoglycerate mutase, a vitally-essential enzyme in glycolysis

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    Models de ratolí; Glucòlisi; Diabetis mellitusModelos de ratón; Glucólisis; Diabetes mellitusMouse models; Glycolysis; Diabetes mellitusGlycolytic metabolism is closely involved in physiological homeostasis and pathophysiological states. Among glycolytic enzymes, phosphoglycerate mutase (PGAM) has been reported to exert certain physiological role in vitro, whereas its impact on glucose metabolism in vivo remains unclear. Here, we report the characterization of Pgam1 knockout mice. We observed that homozygous knockout mice of Pgam1 were embryonic lethal. Although we previously reported that both PGAM-1 and -2 affect global glycolytic profile of cancers in vitro, in vivo glucose parameters were less affected both in the heterozygous knockout of Pgam1 and in Pgam2 transgenic mice. Thus, the impact of PGAM on in vivo glucose metabolism is rather complex than expected before.This work was supported in part by grants from the Japan Society for the Promotion of Science (Grants No. 26310103 to HK and No. 15K19283 to HK), and by the Japan Agency for Medical Research and Development (AMED), Core Research for Evolutional Science and Technology (CREST JP17gm0610002h0306 to HK). HK; Hiroshi Kondoh

    Explaining Japan's Lack of Green Parties : A Social-Milieu Approach

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    Although Japan is a highly industrialized country, it still lacks any significant green parties. This apparent Japanese exceptionalism in terms of green parties cannot be clarified by such conventional explanations as its electoral institutions, party competition, and degree of post−materialism. This paper will instead utilize the German−developed framework of social−milieu studies to explain this phenomenon. It focuses on green parties’ potential support bases, paying attention to the characteristics of green milieu parties. German milieu studies have found that alternative or techno milieus with high educational and occupational qualifications and left−libertarian value orientations have supported the German Green Party. Our data show that an ironist milieu can be regarded as a potential basis of support for Japanese green parties, as Japanese ironist are more leftist toward political and economic issues and more liberal in their cultural attitudes. However, German alternatives tend to be active, while Japanese ironists tend to be passive and disinclined to participate in various groups or to associate with others. Such passivity inclines them to retreat into their private lives without expressing their left− libertarian value orientation in the political arena. Our findings therefore suggest that a milieu exists that could potentially support Japanese green parties, but that these parties have been failing to gain support from it because of its members’ passivity and apolitical behavior

    新しいカルパイン阻害剤はラット生体位心における緩和な虚血再灌流による左心室機能障害を保護する

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    We have previously indicated that a new soluble calpain inhibitor, SNJ-1945 (SNJ), attenuates cardiac dysfunction after cardioplegia arrest-reperfusion by inhibiting the proteolysis of α-fodrin in in vitro study. Nevertheless, the in vivo study design is indispensable to explore realistic therapeutic approaches for clinical use. The aim of the present in situ study was to investigate whether SNJ attenuated left ventricular (LV) dysfunction (stunning) after mild ischemic-reperfusion (mI-R) in rat hearts. SNJ (60 μmol/l, 5 ml i.p.) was injected 30 min before gradual and partial coronary occlusion at proximal left anterior descending artery. To investigate LV function, we obtained curvilinear end-systolic pressure–volume relationship by increasing afterload 60 min after reperfusion. In the mI-R group, specific LV functional indices at midrange LV volume (mLVV), end-systolic pressure (ESPmLVV), and pressure–volume area (PVAmLVV: a total mechanical energy per beat, linearly related to oxygen consumption) significantly decreased, but SNJ reversed these decreases to time control level. Furthermore, SNJ prevented the α-fodrin degradation and attenuated degradation of Ca2+ handling proteins after mI-R. Our results indicate that improvements in LV function following mI-R injury are associated with inhibition of the proteolysis of α-fodrin in in situ rat hearts. In conclusion, SNJ should be a promising tool to protect the heart from the stunning.博士(医学)・甲617号・平成26年3月17
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