Publications (74) View all
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Article: [Systemic distribution of prorenin and its receptor].
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ABSTRACT: The (pro)renin receptor was first identified as a 350-amino acid protein with a single transmembrane domain. This receptor binds to prorenin to mediate its dual functions: activation of ERK1/2 independently from angiotensin II generation and induction of full enzymatic activity to initiate angiotensin II-dependent effects. (Pro) renin receptor has recently been shown to undergo intracellular processing, such that it exists in three different molecular forms. These include the full-length (pro)renin receptor, truncated amino-terminal soluble fragment, and carboxy-terminal fragment containing an accessory protein of the vacuolar-type H(+)-ATPase. Their exact distributions and existing molecular forms remain to be determined.Nippon rinsho. Japanese journal of clinical medicine 09/2012; 70(9):1483-6. -
Article: Salusin-β accelerates inflammatory responses in vascular endothelial cells via NF-κB signaling in LDL receptor-deficient mice in vivo and HUVECs in vitro.
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ABSTRACT: The bioactive peptide salusin-β is highly expressed in human atheromas; additionally, infusion of antiserum against salusin-β suppresses the development of atherosclerosis in atherogenic mice. This study examined the roles of salusin-β in vascular inflammation during atherogenesis. Infusion of antiserum against salusin-β attenuated the induction of VCAM-1, monocyte chemoattractant protein (MCP)-1, and IL-1β and as well as nuclear translocation of NF-κB in aortic endothelial cells (ECs) of LDL receptor-deficient mice, which led to the prevention of monocyte adhesion to aortic ECs. In vitro experiments indicated that salusin-β directly enhances the expression levels of proinflammatory molecules, including VCAM-1, MCP-1, IL-1β, and NADPH oxidase 2, as well as THP-1 monocyte adhesion to cultured human umbilical vein ECs (HUVECs). Both salusin-β-induced VCAM-1 induction and monocyte/HUVEC adhesion were suppressed by pharmacological inhibitors of NF-κB, e.g., Bay 11-7682 and curcumin. Furthermore, the VCAM-1 induction was significantly prevented by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY-294002, whereas it was accelerated by the ERK inhibitor, U-0126. Treatment of HUVECs with salusin-β, but not with salusin-α, accelerated oxidative stress and nuclear translocation of NF-κB as well as phosphorylation and degradation of IκB-α, an endogenous inhibitor of NF-κB. Thus, salusin-β enhanced monocyte adhesion to vascular ECs through NF-κB-mediated inflammatory responses in ECs, which can be modified by PI3K or ERK signals. These findings are suggestive of a novel role of salusin-β in atherogenesis.AJP Heart and Circulatory Physiology 05/2012; 303(1):H96-105. · 3.71 Impact Factor -
Article: Prolonged effects of intracerebroventricular angiotensin II on drinking, eating and locomotor behavior in mice.
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ABSTRACT: The effects of centrally administered Angiotensin II (Ang II) on water and food intake in rodent models are well known. However, most studies have focused on the acute effects of intracranial Ang II. In the current study, we evaluated the effects of intracerebroventricular Ang II on food and water intake as well as locomotor activity over the entire dark phase of the murine diurnal cycle. Consistent with the previous reports, centrally administered Ang II rapidly stimulated water intake over the initial 1-hour period following treatment. However, this acute increase was immediately followed by a marked reduction in water intake resulting in decreased cumulative water intake approximately 7h after Ang II treatment. Pretreating animals with an Ang II type 1 receptor blocker, Losartan, completely antagonized the acute effect of Ang II and abolished initial water intake. In contrast, application of an Ang II type 2 receptor blocker, PD123319, abrogated the prolonged inhibitory effect of Ang II on drinking behavior and partially suppressed the initial increases in water intake. The suppressive effects of Ang II on cumulative food intake and spontaneous physical activity were also evident throughout the entire dark phase of diurnal cycle. These experiments are the first to suggest that the stimulatory effect of central Ang II treatment on water consumption is very temporary and that it causes a sustained suppressive effect on voluntary locomotion and food intake behavior in mice.Regulatory Peptides 01/2012; 173(1-3):86-92. · 2.11 Impact Factor -
Article: Endogenous bioactive peptides as potential biomarkers for atherosclerotic coronary heart disease.
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ABSTRACT: Cardiovascular disease is the leading cause of death worldwide, with high medical costs and rates of disability. It is therefore important to evaluate the use of cardiovascular biomarkers in the early diagnosis of coronary artery disease (CAD). We have screened a variety of recently identified bioactive peptides candidates in anticipation that they would allow detection of atherosclerotic CAD. Especially, we have focused on novel anti-atherogenic peptides as indicators and negative risk factors for CAD. In vitro, in vivo and clinical studies indicated that human adiponectin, heregulin-β(1), glucagon-like peptide-1 (GLP-1), and salusin-α, peptides of 244, 71, 30, and 28 amino acids, respectively, attenuate the development and progression of atherosclerotic lesions by suppressing macrophage foam cell formation via down-regulation of acyl-coenzyme A: cholesterol acyltransferase-1. Circulating levels of these peptides in the blood are significantly decreased in patients with CAD compared to patients without CAD. Receiver operating characteristic analyses showed that salusin-α is a more useful biomarker, with better sensitivity and specificity, compared with the others for detecting CAD. Therefore, salusin-α, heregulin-β(1), adiponectin, and/or GLP-1, alone or in various combinations, may be useful as biomarkers for atherosclerotic CAD.Sensors 01/2012; 12(4):4974-85. · 1.74 Impact Factor -
Article: New indices for predicting glycaemic variability.
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ABSTRACT: Blood glucose variability is known to be associated with increased risk of long-term complications. Reliable indices for predicting hyperglycaemic and hypoglycaemic fluctuations are therefore needed. Glycaemic standard deviation (SD) obtained by continuous glucose monitoring correlates closely with nine previously described glycaemic variability formulas. Here, new indices predictive of glycaemic variability were developed, which can be calculated from laboratory measures based on a single blood draw. The indices included the glycated albumin (GA) to HbA1c ratio (GA/A1c ratio) and the fasting C-peptide immunoreactivity (FCPR) to fasting plasma glucose (FPG) ratio (FCPR index). Predictive values of these indices were assessed in 100 adults with diabetes. GA/A1c ratio and FCPR index showed close associations with glycaemic SD in addition to the nine existing glucose variability formulas. Subjects with a GA/A1c ratio ≥2.8 and FCPR index <3.0 showed the greatest SD and longest durations of hypoglycaemia, while those with a GA/A1c ratio <2.8 and FCPR index ≥3.0 had smaller SDs and little sign of hypoglycaemia. In adults with diabetes, a high GA/A1c ratio and low FCPR index value reflect higher glycaemic excursions, irrespective of diabetes type. Simultaneous measurements of GA, HbA1c, FPG and FCPR may help to identify a group of patients who warrant closer monitoring in relation to glycaemic variability and hypoglycaemia.PLoS ONE 01/2012; 7(9):e46517. · 4.09 Impact Factor
