Kagawa University

About: Kagawa University is a education organization based out in Takamatsu, Japan. It is known for research contribution in the topics: Cancer & Population. The organization has 6028 authors who have published 11918 publications receiving 224111 citations. The organization is also known as: Kagawa Daigaku.

Differential Regulatory Mechanism of Ca2+/Calmodulin-Dependent Protein Kinase Kinase Isoforms

Abstract: We have previously demonstrated that the alpha isoform of Ca(2+)/calmodulin-dependent protein kinase kinase (CaM-KKalpha) is strictly regulated by an autoinhibitory mechanism and activated by the binding of Ca(2+)/CaM [Tokumitsu, H., Muramatsu, M., Ikura, M., and Kobayashi, R. (2000) J. Biol. Chem. 275, 20090-20095]. In this study, we find that rat brain extract contains Ca(2+)/CaM-independent CaM-KK activity. This result is consistent with an enhanced Ca(2+)/CaM-independent activity (60-70% of total activity) observed with the recombinant CaM-KKbeta isoform. By using various truncation mutants of CaM-KKbeta, we have identified a region of 23 amino acids (residues 129-151) located at the N-terminus of the catalytic domain as an important regulatory element of the autonomous activity. A CaM-KKbeta deletion mutant of this domain shows a significant increase of Ca(2+)/CaM dependency for the CaM-KK activity as well as for the autophosphorylation activity. The activities of CaM-KKalpha and CaM-KKbeta chimera, in which autoinhibitory sequences were replaced by each other, were completely dependent on Ca(2+)/CaM, suggesting that the autoinhibitory regions of CaM-KKalpha and CaM-KKbeta are functional. These results establish for the first time that residues 129-151 of CaM-KKbeta participate in the release of the autoinhibitory domain from its catalytic core, resulting in generation of autonomous activity.

The Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Sympathetic Nervous Activity.

Abstract: The EMPA-REG OUTCOME study revealed that a sodium-glucose cotransporter 2 (SGLT2) inhibitor, empagliflozin, can remarkably reduce cardiovascular (CV) mortality and heart failure in patients with high-risk type 2 diabetes. Recently, the CANVAS program also showed that canagliflozin, another SGLT2 inhibitor, induces a lower risk of CV events. However, the precise mechanism by which an SGLT2 inhibitor elicits CV protective effects is still unclear. Possible sympathoinhibitory effects of SGLT2 inhibitor have been suggested, as significant blood pressure (BP) reduction, following treatment with an SGLT2 inhibitor, did not induce compensatory changes in heart rate (HR). We have begun to characterize the effects of SGLT2 inhibitor on BP and sympathetic nervous activity (SNA) in salt-treated obese and metabolic syndrome rats, who develop hypertension with an abnormal circadian rhythm of BP, a non-dipper type of hypertension, and do not exhibit a circadian rhythm of SNA. Treatment with SGLT2 inhibitors significantly decreased BP and normalized circadian rhythms of both BP and SNA, but did not change HR; this treatment was also associated with an increase in urinary sodium excretion. Taken together, these data suggest that an SGLT2 inhibitor decreases BP by normalizing the circadian rhythms of BP and SNA, which may be the source of its beneficial effects on CV outcome in high-risk patients with type 2 diabetes. In this review, we briefly summarize the effects of SGLT2 inhibitors on BP and HR, with a special emphasis on SNA.

Polyamines-induced aluminum tolerance in mung bean: A study on antioxidant defense and methylglyoxal detoxification systems

Abstract: We investigated the roles of exogenously applied Spd (0.3 mM spermidine) in alleviating Al (AlCl3, 0.5 mM, 48 and 72 h)- induced injury in mung bean seedlings (Vigna radiata L. cv. BARI Mung-2). Aluminum toxicity induced oxidative damage overproducing reactive oxygen species (ROS; H2O2 and O2•-), increasing lipoxygenase activity and membrane lipid peroxidation. The toxic compound methylglyoxal (MG) also overproduced under Al stress. In order to circumvent Al-induced oxidative stress, enzymatic and non-enzymatic antioxidant defense were activated by the application of exogenous Spd. Exogenous Spd increased ascorbate (AsA) and glutathione (GSH) content, AsA/dehydroascorbate (DHA) ratio, GSH/ glutathione disulfide (GSSG) ratio, activity of ascorbate peroxidase (APX), dehydroascorbate reductase (DHAR), glutathione reductase (GR) and catalase (CAT) which reduced ROS production and oxidative stress under Al stress. Spd-induced improvement of GSH pool and Gly II activity alleviated injurious effects of MG. Exogenous Spd positively modulated the endogenous PAs level. Regulating the osmoprotectant molecule (proline), Spd improved plant water status under Al stress. Exogenous Spd was potent to prevent breakdown of Al-induced photosynthetic pigment and to improve growth performances under Al stress. The mechanism by which Spd enhances antioxidant and glyoxalase components might be studied extensively. Spermidine-induced protection of photosynthetic pigment from damages and growth enhancement were remarkable and recommended for further detailed study to understand the mechanism.