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Biomedical subjects

Sadayoshi Ito

Publications and source records attributed to Sadayoshi Ito.

At least 37 records · Page 2Linked to original sources
PubMed2005

Upregulation of nitric oxide production in vascular endothelial cells by all-trans retinoic acid through the phosphoinositide 3-kinase/Akt pathway.

BACKGROUND: A natural retinoid all-trans retinoic acid (ATRA) contains various beneficial effects on vasculature, including suppression of neointima formation after balloon injury. However, little is known about the effects of ATRA on vascular endothelial function. We therefore studied its role in nitric oxide (NO) production of vascular endothelial cells (ECs). METHODS AND RESULTS: Human dermal microvascular ECs, human umbilical vein ECs, and SV40-transformed rat lung vascular ECs were incubated with or without ATRA (1 micromol/L) for 48 hours. Their NO production was determined with the use of a fluorescent NO indicator, diaminofluorescein-2 diacetate. ATRA significantly increased their basal as well as acetylcholine-induced NO production. Treatment with Nomega-nitro-L-arginine methyl ester or carboxy-PTIO suppressed their fluorescence. Increase of NO production was also observed by incubation with retinoic acid receptor (RAR) agonist Am580. ATRA-induced NO increase was abolished by coincubation with RAR antagonist LE540. Moreover, the NO increase was completely inhibited by the phosphoinositide 3-kinase (PI3K) inhibitor wortmannin and LY294002. ATRA as well as Am580 enhanced endothelial NO synthase (eNOS) phosphorylation at Ser-1177 as well as Akt phosphorylation at Ser-473 without changing their protein expression. Overexpression of dominant-negative Akt inhibited the eNOS phosphorylation. Moreover, ATRA increased PI3K activity as well as PI3K catalytic subunit p110beta protein expression, which was completely inhibited by LE540 treatment. Real-time polymerase chain reaction analyses demonstrated that ATRA increased PI3K catalytic subunit p110beta mRNA expression without affecting its stability. Finally, ATRA-induced NO increase was observed in COS-1 cells transfected with wild-type eNOS and RARalpha, but not with mutated eNOS whose Ser-1177 was substituted. CONCLUSIONS: ATRA increases NO production by eNOS phosphorylation through RAR-mediated PI3K/Akt pathway activation in vascular ECs and possibly plays beneficial roles in vascular endothelium. Retinoids may therefore be candidates as novel therapeutic agents against vascular disorders with endothelial damage.

Cells, Cultured↗
PubMed2005

PDZ-binding and di-hydrophobic motifs regulate distribution of Kir4.1 channels in renal cells.

It was shown previously that the carboxyl-terminal cytoplasmic portion of Kir4.1 determines the localization of basolateral K+ channel in renal distal tubules, which is composed from the assembly of Kir4.1 and Kir5.1. For clarifying the signals for this localization, specific sequence motifs of Kir4.1 were sought. In HEK293T cells, where Kir4.1 showed linear expression on the cell surface, disruption of the carboxyl-terminal PDZ-binding motif induced mostly clustered distribution but did not reduce whole-cell channel activity. Point mutation analysis revealed that serine377 in this motif was responsible for the surface vicinity expression. Disruption of the di-hydrophobic array of valine333/valine334 induced diffuse cytoplasmic distribution and diminished channel activity. Both valine333 and valine334 contributed to this effect. In contrast to the di-hydrophobic motifs of other membrane proteins that facilitate the sorting, valine333/valine334 supported the cell-surface retention. Because both the PDZ-binding and di-hydrophobic motifs participated in the basolateral expression of both Kir4.1 homomer and Kir5.1/Kir4.1 heteromer in MDCK cells, they are thought to be responsible for the localization of basolateral K+ channel in renal distal tubules.

Amino Acid Motifs↗
PubMed2005

Cytochrome P-450-dependent metabolism of arachidonic acid in the kidney of rats with diabetes insipidus.

This study compared the renal metabolism of arachidonic acid in Brattleboro (BB) (vasopressin deficient) and Long-Evans (LE) control rats and the effects of a cytochrome P-450 (CYP) inhibitor 1-aminobenzotriazole (ABT) on renal function in these animals. The production of 20-hydroxyeicosatetraenoic acid (20-HETE) by renal cortical and outer medullary microsomes was significantly greater in BB than in LE rats (155 +/- 16 vs. 92 +/- 13 and 59 +/- 7 vs. 33 +/- 3 pmol.min(-1).mg protein(-1)). Renal cortical epoxygenase activity was not different in these strains. The expression of CYP4A proteins was 58 and 78% higher in the renal cortex and outer medulla of BB than in LE rats. Chronic treatment of BB rats with a vasopressin type 2 receptor agonist for 1 wk normalized the renal production of 20-HETE. Chronic blockade of the formation of 20-HETE and EETs with ABT had little effect on renal function in LE rats. However, urine flow increased by 54% and urine osmolarity decreased by 33% in BB rats treated with ABT. Plasma levels of oxytocin fell significantly from 7.2 +/- 1.3 to 3.9 +/- 1.0 pg/ml. The effects of ABT in BB rats were attenuated by chronic infusion of oxytocin (0.7 ng.min(-1).100 g(-1)) to maintain fixed high plasma levels of this hormone. These results indicate that the expression of CYP4A protein and the renal formation of 20-HETE are elevated in the kidney of BB rats due to a lack of vasopressin and that chronic blockade of the formation of 20-HETE and EETs with ABT promotes water excretion in vasopressin-deficient BB rats by reducing the circulating levels of oxytocin, which is a weak vasopressin agonist.

8,11,14-Eicosatrienoic Acid↗
PubMed2005

[Hypertension].

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Humans↗
PubMed2005

Steroid resistance in prolonged type I membranoproliferative glomerulonephritis and accelerated disease remission after steroid withdrawal.

Two cases of severe proteinuria and hypocomplementemia were referred to our out patient clinic for continuous follow-up. Initial onset of clinical symptoms was at the age of 15 years in both cases. They had already been diagnosed as type I membranoproliferative glomerulonephritis (type I MPGN) by renal biopsy when oral prednisolone administration had been initiated. Several courses of steroid pulse therapy were performed for the flares of the disease, resulting in only temporary amelioration of renal symptoms. Percutaneous renal biopsy was performed during admission on both cases, showing severe glomerular and tubulointerstitial damages, in addition to typical type I MPGN findings such as mesangial cells and matrix interposition and subendothelial deposits. Because the continuous administration of steroid for more than 10 years did not ameliorate the clinical symptoms, steroid was markedly reduced or stopped in these cases. Such withdrawal from steroid therapy accelerated the amelioration of renal symptoms, including decrease in proteinuria, elevation of plasma protein and complement levels, and disappearance of generalized edema. The clinical courses of these cases indicate clinical choice of withdrawal from steroid therapy as one of the treatments in prolonged type I MPGN, which presents in childhood and shows steroid resistance.

Adolescent↗
PubMed2005

Cutting balloon angioplasty of resistant renal artery stenosis caused by fibromuscular dysplasia.

Balloon angioplasty is an established intervention to treat renovascular hypertension. Conventional balloon angioplasty is usually effective in cases of renovascular hypertension caused by fibromuscular dysplasia. In the present report, we describe two cases of renovascular hypertension caused by fibromuscular dysplasia in which stenotic lesions were resistant to conventional balloon angioplasty but were successfully managed by a cutting balloon. After cutting balloon angioplasty, systemic blood pressure was normalized in both patients, without the use of antihypertensive agents. Angioplasty by using a cutting balloon is a new therapeutic choice against renal artery stenosis that is resistant to dilation by a conventional balloon.

Adolescent↗
PubMed2005

Plasma renin activity revealed renal artery stenosis concealed by aneurysms.

We describe a case of renovascular hypertension with renal artery stenosis concealed by aneurysms. Arteriography demonstrated no apparent renal artery stenosis, but did reveal aneurysms on the left renal artery. Captopril-loaded renoscintigraphy could not detect disturbed renal perfusion. High basal and exaggerated plasma renin activity after captopril administration were the only clues indicating renovascular hypertension. A reduction of the systemic blood pressure and normalized plasma renin activity after resection of the aneurysms confirmed preoperative renovascular hypertension. Fibromuscular dysplasia was an underlying cause of the arterial deformity. In cases of hypertension accompanied by renal artery aneurysms, the captopril-challenge test can be a useful tool to detect renal artery stenosis concealed by the aneurysms.

Adult↗
PubMed2005

Protective effect of peroxisome proliferator activated receptor gamma agonists on diabetic and non-diabetic renal diseases.

Peroxisome proliferator activated receptor gamma (PPARgamma) agonist has not only antidiabetic effect but also a protective effect against various types of injury of the kidney. The protective effects of PPARgamma agonists are observed in diabetic nephropathy and non-diabetic renal diseases such as 5/6 ablation model of renal failure, experimental glomerulonephritis, ischemia-reperfusion injury, hypertensive nephropathy and cyclosporin-induced renal injury. The mechanism of renoprotection by PPARgamma agonist is multifactorial. Anti-fibrotic and anti-inflammatory effects, suppression of renin-angiotensin system, vascular protective effect and antiapoptotic effect were proposed.

Animals↗
PubMed2005

Rosiglitazone protects against cyclosporine-induced pancreatic and renal injury in rats.

Rosiglitazone (RGTZ) has protective effect against various types of injury. This study was performed to evaluate the effect of RGTZ on pancreatic and renal injury caused by cyclosporine (CsA). CsA (15 mg/kg) and RGTZ (3 mg/kg) were administered alone and together to the rats for 28 days. The effect of RGTZ on CsA-induced pancreatic injury was evaluated by intraperitoneal glucose tolerance test (IPGTT), plasma insulin concentrations and pancreatic beta-cell morphology. The effect of RGTZ on CsA-induced renal injury was evaluated by assessing renal function and pathology; mediators of inflammation and fibrosis such as angiotensin II (AngII), osteopontin (OPN) and transforming growth factor-beta1 (TGF-beta1) and apoptotic cell death. Four weeks of CsA treatment caused diabetes, renal dysfunction, typical pathologic lesions (arteriolopathy, interstitial fibrosis and inflammatory cells infiltration) and apoptotic cell death. RGTZ treatment decreased blood glucose concentration, increased plasma insulin concentration and preserved pancreatic beta islet mass. RGTZ treatment improved renal function and histopathology. Pro-inflammatory and pro-fibrotic molecules such as AngII, OPN and TGF-beta1, and apoptotic cell death also decreased with RGTZ treatment. These data suggest that RGTZ has a protective effect against CsA-induced pancreatic and renal injury.

Angiotensin II↗
PubMed2005

Predictors of undiagnosed renal artery stenosis among Japanese patients with risk factors of atherosclerosis.

Atherosclerotic renal artery stenosis (ARAS) is a significant cause of end stage renal dysfunction (ESRD) among the elderly. Although early detection of ARAS and induction of adequate treatment could reduce the incidence of ESRD, there have been few reports about parameters predictive of ARAS among Japanese. In this study, we investigated the clinical indicators that predict ARAS among Japanese with risk factors of atherosclerosis (> 40 years of age plus hypertension, dyslipidemia or diabetes mellitus). After eliminating the patients who had already been diagnosed with renal artery stenosis, 202 patients were enrolled. The renal arteries of all 202 patients were evaluated by magnetic resonance arteriography (MRA), and the stenoses with > 50% reduction in diameter at the ostium of the renal artery were defined as ARAS. MRA detected ARAS in 42 patients (31 hemilateral and 11 bilateral). Between the patients with and without ARAS there was no significant difference in gender distribution, detection of abdominal vascular bruits or smoking habit. The prevalences of diabetic, hypertensive and cerebrovascular comorbidity were also not significantly different. The mean blood pressure, body mass index and total serum cholesterol values were similar between the two groups. However, age, pulse pressure, serum uric acid, serum creatinine, amount of urinary protein, and coronary artery comorbidity were significantly higher, while estimated creatinine clearance was significantly lower in the patients with ARAS than in those without ARAS. A high prevalence of hypertensive retinopathy was also noted among patients with ARAS. Multivariate analysis revealed that older age and renal impairment were independent predictors of ARAS in Japanese patients with atherosclerotic risk factors.

Aged↗
PubMed2005

Renal artery dissection after angiographic evaluation of lower extremities.

We describe a case of renovascular hypertension that was caused by renal artery dissection after an angiographic evaluation of the lower extremities. Retention of contrast medium in the affected kidney even 1 day after the procedure caused us to suspect renal artery dissection. Magnetic resonance angiography revealed irregular streaks in the lumen of the affected artery, a sign of dissection. Treatment by a transluminal angioplasty with stent insertion improved renal function and reduced systemic blood pressure with normalization of plasma renin activity. In patients whose systemic blood pressure increases suddenly after any conceivable physical traction on the abdominal aorta, evaluation of the renal arteries should be considered. Appropriate endovascular treatment can preserve renal function and reduce systemic blood pressure.

Aged↗
PubMed2005

Autoinduction of tumor necrosis factor-alpha in FRTL-5 rat thyroid cells.

Tumor necrosis factor-alpha (TNFalpha) may play a role in the development of autoimmune thyroiditis such as Hashimoto's thyroiditis. In the present study, we examined whether TNFalpha induced its own expression in FRTL-5 rat thyroid cells. Lipopolysaccharide (LPS) markedly increased TNFalpha mRNA levels in FRTL-5 cells as assessed by semiquantitative RT-PCR. In addition, LPS-stimulated cells released TNFalpha protein into the culture medium. Similarly, TNFalpha induced its own gene and protein expression in FRTL-5 cells as assessed by RT-PCR and metabolic labeling and immunoprecipitation of TNFalpha. The autoinduction of TNFalpha gene was also observed in TNFalpha-stimulated human thyroid epithelial cells. TNFalpha induction was specific to LPS and TNFalpha since interferon-alpha or amiodarone failed to increase TNFalpha mRNA levels in FRTL-5 cells. Human TNFalpha induced rat TNFalpha gene expression, indicating that type 1 TNF receptor (TNF-R) is involved in the autoinduction. TNFalpha did not increase either type 1 or type 2 TNF-R mRNA levels, suggesting that upregulation of TNF receptors is not involved in the autoinduction of TNFalpha. Although the biological significance of autoinduction of TNFalpha remains unclear, our results suggest that thyroid epithelial cells may participate in the development of autoimmune thyroiditis through production of TNFalpha. Furthermore, inhibition of TNFalpha production in the thyroid may represent a novel approach to mitigating inflammation in autoimmune thyroiditis.

Actins↗
PubMed2005

[The vasoactive systems in the regulation of renal hemodynamics].

In the homeostasis of sodium and water metabolism, the kidney plays a pivotal role. It is the center of multiple humoral systems, such as renin angiotensin aldosterone system, arginine vasopressin, atrial natriuretic peptide, and nitric oxide, which control both systemic and renal circulation in concert. Disturbances in these systems secondary to cardiovascular compromise, especially hemodynamic insufficiency in renal circulation, lead to the accumulation of excess sodium and water, resulting in edema formation. So it is crucial to elucidate the relationship between the kidney and these vasoactive systems for the better understanding of pathophysiology of edema and volume retension.

Arginine Vasopressin↗
PubMed2005

[Reninoma].

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Adult↗