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Biomedical subjects

Ichiro Nishio

Publications and source records attributed to Ichiro Nishio.

At least 37 records · Page 2Linked to original sources
PubMed2004

Leptin and membrane fluidity of erythrocytes in essential hypertension. An electron paramagnetic resonance investigation.

There has been an indication that leptin, the product of the human obesity gene, actively participates not only in metabolic regulation but also in the control of blood pressure. Recently, it has been proposed that abnormalities in the physical property of cell membranes may underlie the defects that are strongly linked to hypertension, stroke, and other cardiovascular diseases. We have shown previously that leptin significantly increased the membrane fluidity and improved the microviscosity of erythrocytes in humans through the nitric oxide-dependent mechanism. In the present study, we examined the effects of leptin on membrane fluidity of erythrocytes in subjects with essential hypertension by means of an electron paramagnetic resonance (EPR) and spin-labeling method. The values of the order parameter (S) and the peak height ratio (ho/h-1) obtained from the EPR spectra of erythrocytes were significantly greater in patients with essential hypertension (HT) than in age-matched normotensive subjects (NT) (S: HT 0.719 +/- 0.002, n = 16, NT 0.713 +/- 0.001, n = 29, P < .05; ho/h-1: HT 5.17 +/- 0.02, n = 16, NT 5.05 +/- 0.02, n = 29, P < .05). The finding indicated that the erythrocyte membrane fluidity was lower in patients with HT than in NT. Leptin decreased S and ho/h-1 in a dose-dependent manner in both NTs and HTs. The effect of leptin on the membrane fluidity was significantly more pronounced in HTs than in NTs (percent change in S: leptin 10(-8) g/mL, HT -3.4% +/- 0.2%, n = 16, NT -2.3% +/- 0.1%, n = 29, P < .05; leptin 10(-7) g/mL, HT -4.3% +/- 0.3%, n = 16, NT -3.3% +/- 0.1%, n = 29, P < .05). The results of the present study showed that leptin might have a crucial role in the regulation of the rheologic behavior of erythrocytes and the microcirculation in hypertension.

Biomarkers↗
PubMed2004

A calcium channel blocker, benidipine, improves cell membrane fluidity in human subjects via a nitric oxide-dependent mechanism. An electron paramagnetic resonance investigation.

Recent studies have revealed that benidipine, a long-acting dihydropyridine-type of calcium (Ca) channel blocker, may exert its protective effect against vascular disorders by increasing nitric oxide (NO) production. The purpose of the present study was to investigate the effects of benidipine and NO on the membrane function in human subjects. We measured the membrane fluidity of erythrocytes by using an electron paramagnetic resonance (EPR) and spin-labeling method. Benidipine decreased the order parameter (S) for 5-nitroxide stearate (5-NS) and the peak height ratio (h(o)/h(-1)) for 16-NS obtained from EPR spectra of erythrocyte membranes in a dose-dependent manner in normotensive volunteers. The finding indicated that benidipine increased the membrane fluidity and improved the microviscosity of erythrocytes. The effect of benidipine was significantly potentiated by the NO donor, S-nitroso-n-acetylpenicillamine, and by the cyclic guanosine 3', 5'-monophosphate (cGMP) analog, 8-bromo-cGMP. In contrast, the change evoked by benidipine was counteracted by the NO synthase inhibitors, N(G)-nitro-L-arginine-methyl-ester and asymmetric dimethyl-L-arginine. These results demonstrated that benidipine increased the membrane fluidity of erythrocytes, at least in part, via the NO- and cGMP-dependent mechanism. Furthermore, the data strongly suggest that benidipine might have a beneficial effect on the rheologic behavior of erythrocytes and the improvement of the microcirculation in humans.

Aged↗
PubMed2004

Leptin and nitric oxide production in normotensive and hypertensive men.

OBJECTIVE: Recent findings have shown that leptin, the product of the obesity gene, may actively participate in the regulation of blood pressure and other cardiovascular functions through the nitric oxide (NO)-dependent mechanism. RESEARCH METHODS AND PROCEDURES: In this study, to test the hypothesis that leptin regulation of NO metabolism is impaired in hypertension, we examined the possible relationship between circulating leptin and plasma NO metabolite level in normotensive (NT) and hypertensive (HT) men. RESULTS: There were significant correlations between circulating leptin and BMI in both the NT and HT groups (NT: r = 0.64, n = 26, p < 0.01; HT: r = 0.59, n = 22, p < 0.01). The concentration of circulating leptin was similar between the NT and HT men, although the plasma NO metabolite level (nitrite and nitrate) was significantly reduced in the HT men compared with the NT men (NT: 51.0 +/- 4.9 microM, n = 26; HT: 37.1 +/- 2.5 microM, n = 22, p < 0.05). The circulating leptin was significantly correlated with the plasma NO metabolite level in the overall analysis of the NT and HT men (r = 0.35, n = 48, p < 0.05). When the analysis of the correlation for the NT and HT men was performed separately, there was a significant correlation between circulating leptin and plasma NO metabolites in the NT men (r = 0.45, n = 26, p < 0.05) but not in the HT men (r = 0.15, n = 22). The results of this study are consistent with the hypothesis that leptin-related metabolism of NO might be altered in HT men.

Body Mass Index↗
PubMed2004

Oxidized low-density lipoprotein induces endothelial progenitor cell senescence, leading to cellular dysfunction.

1. Recent studies have revealed an association between coronary risk factors and both the number and function of bone marrow-derived endothelial progenitor cells (EPC). We investigated the effect of oxidized low-density lipoprotein (ox-LDL) on the senescence of EPC, leading to cellular dysfunction. 2. Endothelial progenitor cells were isolated from human peripheral blood and characterized. The exposure of cultured EPC to ox-LDL (10 microg/mL) significantly accelerated the rate of senescence compared with control during 20 days in culture as determined by acidic beta-galactosidase staining. Oxidized LDL-induced EPC senescence was significantly inhibited by pretreatment with either lectin-like ox-LDL receptor-1 (LOX-1) antibody (Ab) or atorvastatin (P < 0.01). 3. Because cellular senescence is critically influenced by telomerase, which elongates telomeres, we measured telomerase activity using a polymerase chain reaction-ELISA-based assay. Oxidized LDL significantly diminished telomerase activity to approximately 50%, an effect that was significantly abolished by pretreatment with either LOX-1 Ab or atorvastatin (P < 0.01). 4. We examined whether ox-LDL-induced EPC senescence translates into EPC dysfunction. An MTS assay disclosed an inhibitory effect of ox-LDL on EPC proliferation. In a Matrigel assay, EPC treated with ox-LDL were less likely to participate in network formation compared with controls. 5. In conclusions, ox-LDL accelerates the onset of EPC senescence, which may be related to telomerase inactivation. Oxidized LDL-induced EPC senescence leads to the impairment of proliferative capacity and network formation.

Atorvastatin↗
PubMed2004

Angiotensin II potentiates vascular endothelial growth factor-induced proliferation and network formation of endothelial progenitor cells.

Bone marrow-derived endothelial progenitor cells (EPCs) in the peripheral blood of adult animals and adult humans have been shown to play a role in neovascularization into neovascular structures. On the other hand, angiotensin II (Ang II) plays a role in the development of many vascular diseases. To investigate whether Ang II affects human vascular endothelial growth factor (VEGF)-induced EPCs proliferation and network formation. Reverse transcription-polymelase chain reaction analysis demonstrated that Ang II induced a significant increase of VEGF receptor kinase domain-containing receptor (KDR) mRNA in a dose- and time-dependent manner; the maximal increase, which was 3-fold the control value, occurred after a 4-h stimulation. In addition, flow cytometric analysis revealed that Ang II up-regulated KDR protein expression in human EPCs. Both the angiotensin type 1 (AT1) receptor antagonist (valsartan: 200 nmol/l) and the PKC inhibitor, bisindolylmaleimide (GFX: 10 micromol/l) reduced Ang II-induced KDR mRNA expression to almost the control level. The culture assay showed that Ang II dose-dependently enhanced VEGF-induced EPC proliferation by activating AT1 receptors, which was also confirmed by the colorimetric MTS assay with the electron coupling reagent mathosulfate. Finally, in a Matrigel assay, EPCs treated with both Ang II and VEGF were shown to be more likely to integrate into the network formation than those treated with VEGF alone. In conclusion, our data indicate that Ang II potentiates VEGF-induced human EPCs proliferation and network formation through the up-regulation of KDR.

Angiotensin II↗
PubMed2003

Nitric oxide is a determinant of membrane fluidity of erythrocytes in postmenopausal women: an electron paramagnetic resonance investigation.

In the present study, to determine a possible role of nitric oxide (NO) in the regulation of membrane functions, we examined the relationship between plasma NO level and membrane fluidity of erythrocytes in postmenopausal women. We evaluated the membrane fluidity of erythrocytes obtained from hypertensive and normotensive postmenopausal women by means of an electron paramagnetic resonance (EPR) and spin labeling method. The EPR study revealed that the order parameter (S) for 5-nitroxide stearate in erythrocyte membranes was significantly greater in hypertensive postmenopausal women than in normotensive postmenopausal women. The finding indicated that the membrane fluidity of erythrocytes was decreased in hypertensive postmenopausal women compared with normotensive postmenopausal women. The plasma level of the NO metabolites (nitrite and nitrate) while fasting was significantly lower in hypertensive postmenopausal women than in normotensive postmenopausal women. In addition, the order parameter (S) in the EPR spectra of erythrocyte membranes was inversely correlated with the plasma NO metabolite level, which indicated that the lower membrane fluidity of erythrocytes was associated with the lower plasma NO level in postmenopausal women. These results are consistent with the hypothesis that NO may have a crucial role in the regulation of membrane fluidity of erythrocytes in postmenopausal women.

Aged↗
PubMed2003

Hormone replacement therapy improves membrane fluidity of erythrocytes in postmenopausal women: an electron paramagnetic resonance investigation.

BACKGROUND: Many studies have shown that hormone replacement therapy (HRT) might provide protection against the development of hypertension and arteriosclerosis in postmenopausal women. However, the precise mechanism underlying its benefits is unclear. This question was addressed in an electron spin resonance (EPR) study of membrane function of erythrocytes in postmenopausal women. The purpose of this study was to investigate the effects of HRT on membrane fluidity of erythrocytes in postmenopausal women by means of the EPR and spin-labeling method. METHODS: The healthy postmenopausal women were randomly divided into the HRT group (n = 14) receiving the conjugated estrogen with medroxyprogesterone for 3 months and the non-HRT control group (n = 14). We measured membrane fluidity of erythrocytes in postmenopausal women before and after the trial period. RESULTS: The HRT group showed a significant decrease in blood pressure (BP) after treatment (systolic BP 145.7 +/- 5.5 v 123.3 +/- 5.1 mm Hg, n = 14, mean +/- SEM, P <.05). The order parameter (S) for 5-nitroxide stearate in the EPR spectra of erythrocyte membranes decreased significantly in the HRT group (S: 0.718 +/- 0.002 v 0.695 +/- 0.002, n = 14, P <.01). The finding indicated that HRT increased the membrane fluidity of erythrocytes and improved the microviscosity of the cell membranes in postmenopausal women. CONCLUSIONS: These results are consistent with the hypothesis that HRT might have a beneficial effect on the membrane rheologic behavior of erythrocytes and the microcirculation in postmenopausal women.

Arteriosclerosis↗
PubMed2003

Inhibition of nuclear translocation of transcription factor nuclear factor-kappa B induces FAS- as well as tumour necrosis factor-alpha-mediated apoptosis through downregulation of a conserved family of inhibitor of apoptosis 1.

1. In the present study, we examined whether the nuclear transcription factor (NF)-kappaB activity plays a role in the determination of sensitivity to tumour necrosis factor (TNF)-alpha or agonistic Fas antibody (Ab) in human vascular smooth muscle cells (hVSMC). 2. To inhibit agonist-induced NF-kappaB activation in hVSMC, a cell-permeable peptide (SN50), which carried the nuclear localization sequence of the NF-kappaB p50 subunit, was used. Nuclear factor-kappaB activity was examined by both immunoblot analysis of nuclear extracts and by ELISA. The hVSMC were treated with TNF-alpha or agonistic Fas Ab (CH11) and then apoptosis was determined by cell death ELISA for DNA fragmentation. To investigate the mechanisms for protection against apoptosis in hVSMC, we analysed the expression of a conserved family of inhibitor of apoptosis 1 (c-IAP1) protein using immunoblot analysis. 3. Although both CH11 and TNF-alpha alone failed to induce hVSMC death in the presence of SN50, they markedly increased the apoptotic hVSMC estimated by cell death ELISA. In addition, these effects could be blocked with the pan-caspase inhibitor z-VAD.fmk. Western blotting analysis indicated that TNF-alpha alone increased c-IAP1 protein levels, whereas CH11 alone had no effect. Inhibition of NF-kappaB activation by SN50 suppressed c-IAP1 protein expression and enhanced apoptosis induced by either TNF-alpha or CH11. 4. These findings suggest that c-IAP1 is an important intracellular modulator of Fas as well as TNF-alpha death signalling pathways in hVSMC. The expression of c-IAP1 is regulated by a NF-kappaB-mediated phenomenon.

Active Transport, Cell Nucleus↗