Biomedical subjects

Hideo Kanehara

Publications and source records attributed to Hideo Kanehara.

6 recordsLinked to original sources

PubMed2004

Function of hormone-sensitive lipase in diacylglycerol-protein kinase C pathway.

To explore the functional effects of hormone-sensitive lipase (HSL) in diacylglycerol (DAG) metabolism, Chinese hamster ovary cells were stably transfected with rat HSL cDNA (wt-HSL), inactive mutant S423A-HSL cDNA (S423A) and pcDNA3 vector alone (Ct). [(14)C]Glucose-incorporation into triglyceride (TG) was 75% lower in the presence or absence of insulin in cells expressing wt-HSL compared to Ct or S423A. [(14)C]Glucose-incorporation into DAG was 33% lower without insulin and 51% lower with insulin in cells expressing wt-HSL compared to Ct or S423A. Insulin stimulated glucose-incorporation into DAG 2.2-fold in S423A and Ct cells, whereas only a 50% increase was observed in cells expressing wt-HSL. Phospholipase C-mediated release of DAG from membrane phospholipids was reduced 70% in cells expressing wt-HSL compared to Ct or S423A. Western blot analysis showed that membrane-bound protein kinase C (PKC)-alpha and -epsilon were decreased 40-50% in cells expressing wt-HSL grown in high glucose with insulin. These data show that HSL potentially hydrolyzes cellular DAG generated either by de novo synthesis from glucose or release from membrane phospholipids by phospholipase C, resulting in a reduction in the translocation of DAG-sensitive PKCs.

Animals↗

PubMed2004

[HDL cholesterol].

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Apolipoprotein A-I↗

PubMed2003

Pitavastatin-induced thrombomodulin expression by endothelial cells acts via inhibition of small G proteins of the Rho family.

OBJECTIVE: 3-hydroxyl-3-methyl coenzyme A reductase inhibitors (statins) can function to protect the vasculature in a manner that is independent of their lipid-lowering activity. The main feature of the antithrombotic properties of endothelial cells is an increase in the expression of thrombomodulin (TM) without induction of tissue factor (TF) expression. We investigated the effect of statins on the expression of TM and TF by endothelial cells. METHODS AND RESULTS: The incubation of endothelial cells with pitavastatin led to a concentration- and time-dependent increase in cellular TM antigen and mRNA levels. In contrast, the expression of TF mRNA was not induced under the same conditions. A nuclear run-on study revealed that pitavastatin accelerates TM transcription rate. The stimulation of TM expression by pitavastatin was prevented by either mevalonate or geranylgeranylpyrophosphate. Specific inhibition of geranylgeranyltransferase-I and Rac/Cdc42 by GGTI-286 and Clostridium sordellii lethal toxin, respectively, enhanced TM expression, whereas inactivation of Rho by Clostridium botulinum C3 exoenzyme was ineffective. CONCLUSIONS: Statins regulate TM expression via inhibition of small G proteins of the Rho family; Rac/Cdc42. A statin-mediated increase in TM expression by endothelial cells may contribute to the beneficial effects of statins on endothelial function.

Bacterial Proteins↗

PubMed2003

Effect of cilostazol on impaired vasodilatory response of the brachial artery to ischemia in smokers.

The vascular endothelial function of smokers is known to be impaired. This study investigated whether cilostazol could improve the vasodilatory response of the brachial artery to ischemia, an indicator of endothelial function, in ten male smokers. Endothelium-dependent vasodilatation and endothelium-independent vasodilatation of the brachial artery were measured in 11 male non-smokers and 20 male smokers with matching age and weight. The results showed that the vasodilatory response to reactive hyperemia was significantly smaller in the smokers (4.8 +/- 1.6%) when compared to that in the non-smokers (7.6 +/- 2.5%) (p = 0.0013). However, no significant difference in the vasodilatory response to isosorbide dinitrate was observed between the two groups. In addition, there were no significant differences in serum lipid, Lp (a), or blood homocysteine between the smokers and non-smokers. When 150 mg/day of cilostazol was administered for two weeks, the vasodilatory response to reactive hyperemia significantly improved (4.2 +/- 1.2% to 7.8 +/- 3.5%, p = 0.0032). The increased vasodilatory response to reactive hyperemia by cilostazol was reduced after cessation of the drug (4.5 +/- 1.5%). These findings suggest that cilostazol improves vascular endothelial dysfunction in smokers.

Adult↗

PubMed2002

Thrombomodulin expression by THP-1 but not by vascular endothelial cells is upregulated by pioglitazone.

Thrombomodulin-protein C pathway is a major anti-thrombotic mechanism present in endothelial cells (EC), and an important modulator of inflammation. Peroxisomal proliferator activated receptor-gamma (PPARgamma) expressed in monocytes/macrophages may have a role in cell differentiation. Since the expression of thrombomodulin (TM) by monocytes is upregulated during differentiation into macrophages, we investigated the effect of pioglitazone, a thiazolidinedione (TZD) that is a synthetic ligand of PPARgamma, on the expression of TM by a human monocyte/macrophage cell line; human acute monocytic leukemia (THP-1) cells. Pioglitazone dose-dependently upregulated TM antigen expression by THP-1 cells accompanied by an upregulation of TM cofactor activity for thrombin-dependent protein C activation. Thrombomodulin mRNA expression in THP-1 cells was also upregulated by pioglitazone, whereas tissue factor (TF) mRNA expression was not induced at all. Treatment cells with a natural PPARgamma ligand, 15-deoxy-delta12,14-prostaglandin J(2) (PGJ2), also enhanced TM protein expression. PGF(2alpha) an agent known to inactivate PPARgamma, diminished the stimulatory effect of pioglitazone and PGJ2 on TM protein expression. In contrast, pioglitazone had no effect on TM antigen expression by human umbilical vein ECs. These results suggest that PPARgamma activation in macrophages may counteract potentially prothrombotic and putative inflammatory properties in activated macrophages.

Antibodies, Monoclonal↗

PubMed2002

Cardiac gene expression profile and lipid accumulation in response to starvation.

Starvation induces many biochemical and histological changes in the heart; however, the molecular events underlying these changes have not been fully elucidated. To explore the molecular response of the heart to starvation, microarray analysis was performed together with biochemical and histological investigations. Serum free fatty acids increased twofold in both 16- and 48-h-fasted mice, and cardiac triglyceride content increased threefold and sixfold in 16- and 48-h-fasted mice, respectively. Electron microscopy showed numerous lipid droplets in hearts of 48-h-fasted mice, whereas fewer numbers of droplets were seen in hearts from 16-h-fasted mice. Expression of 11,000 cardiac genes was screened by microarrays. More than 50 and 150 known genes were detected by differential expression analysis after 16- and 48-h-fasts, respectively. Genes for fatty acid oxidation and gluconeogenesis were increased, and genes for glycolysis were decreased. Many other genes for metabolism, signaling/cell cycle, cytoskeleton, and tissue antigens were affected by fasting. These data provide a broad perspective of the molecular events occurring physiologically in the heart in response to starvation.

Animals↗