• Nutrition Research and Practice
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• v.11 no.5
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• pp.388-395
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• 2017

BACKGROUND/OBJECTIVES: Although Korean fermented foods contain large amounts of salt, which is known to exacerbate health problems, these foods still have beneficial effects such as anti-hypertension, anti-cancer, and anti-colitis properties. We hypothesized that ganjang may have different effects on blood pressure compared to same concentrations of salt. MATERIALS/METHODS: Sprague-Dawley rats were divided into control (CT), NaCl (NC), and ganjang (GJ) groups and orally administered with 8% NaCl concentration for 9 weeks. The systolic blood pressure (SBP), serum chemistry, $Na^+$ and $K^+$ concentrations and renal gene expressions were measured. RESULTS: The SBP was significantly increased in the NC group compared to the GJ and CT groups. In addition, the $Na^+$ concentration in urine was higher in the GJ and NC groups than the CT group, but the urine volume was increased in the GJ group compared to the other groups. The serum renin levels were decreased in the GJ group compared to the CT group, while the serum aldosterone level was decreased in the GJ group relative to the NC group. The mRNA expression of the renin, angiotensin II type I receptor, and mineralocorticoid receptor were significantly lower in the GJ group compared to other groups. Furthermore, GJ group showed the lowest levels of genes for $Na^+$ transporter in kidney cortex such as $Na^+/K^+$ $ATPase{\alpha}1$ ($NKA{\alpha}1$), $Na^+/H^+$ exchanger 3 (NHE3), $Na^+/HCO_3{^-}$ co-exchanger (NBC), and carbonic anhydrases II (CAII). CONCLUSIONS: The decreased SBP in the GJ could be due to decreased renin and aldosterone levels in serum and increased urinary volume and excretion of $Na^+$ with its transporter gene alteration. Therefore, ganjang may have antihypertensive effect despite its high contents of salt.

• Animal cells and systems
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• v.2 no.4
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• pp.539-543
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• 1998

Hrp1, of Schizosaccharomyces pombe, is a new member of the SW12/SNF2 protein family that contains a chromodomain and a DNA binding domain as well as ATPase/7 helicase domains. This configuration suggests that Hrp1 could be a homolog of mouse CHD1, which is thought to function in altering the chromatin structure to facilitate gene expression. To understand the enzymatic nature of Hrp1 we purified the 6-Histidine-tagged Hrp1 protein (6$\times$His-Hrp1) to homogeneity from a S. pombe Hrp1-overexpressing strain and hen examined its biochemical properties. We demonstrate that the purified 6$\times$His-Hrp1 protein exhibited a DNA-binding activity with a moderate preference to the (A＋T)-rich tract in double-stranded NA via a minor groove interaction. However, we failed to detect any intrinsic DNA helicase activity from the purified Hrp1 like other SW12/SNF2 proteins. These observations suggest that the DNA binding activities of Hrp1 may be involved in the remodeling of the chromatin structure with DNA-dependent ATPase. We propose that Hrp1 may function in heterochromatins as other proteins with a chromo- or ATPase/helicase domain and play an important role in the determination of chromatin architecture.

• Herbal Formula Science
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• v.10 no.1
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• pp.113-129
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• 2002

The present study designed to investigate whether hwangryunhaedok-tang show an anti-hypertensive effect and elucidate its possible mechanism in spontaneously hypertensive rats. The systolic blood pressures (SBP) were significantly decreased as an oral administration of hwangryunhaedok-tang compared with their control group. The urine volume was significantly increased by administration of hwangryunhaedok-tang but urinary sodium (UNaV), potassium (UKV), chloride excretion (UCIV) were not remarkably affected. The urinary creatinine excretion rate (UcrV) was significantly increased in rats administered with hwangryunhaedok-tang in association with increase of creatinine clearance (Ccr). The urine osmolality (Uosmol) was significantly decreased in SHR administered with hwangryunhaedok-tang without being changed in solute-free water reabsorption ( TcH20). The expressions of Aquaporin 2 (AQP-2). 3 and ${\alpha}\;1$, ${\beta}\;1$ subunits of Na.K-ATPase were determined by Western blot analysis to assess the role of these proteins in association with changes of renal functions in SHR administered with hwangryunhaedok-tang. The expression of AQP-2 and 3 protein was significantly down-regulated in the kidney of SHR administered with hwangryunhaedok-tang compared with those in control rats without being altered expression of ${\alpha}\;1$, ${\beta}\;1$ subunits of Na,K-ATPase. In the in vitro assay, Angiotensin converting enzyme (ACE) was inhibited by hwangryunhaedok-tang in a dose-dependent manner. Berberine and/or palmatine, which are well known as a main components of hwangryunhaedok-tang, also have an ACE inhibitory effects in a dose-dependent manner. Taken together, these results suggest that hwangryunhaedok-tang lowered blood pressure through the increase of diuresis caused by down-regulation of water channels and the inhibition of Angiotensin converting enzyme.

• Journal of Photoscience
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• v.4 no.2
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• pp.41-48
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• 1997

The plasma membrane and microsomes, isolated from the cells treated with hematoporphyrm derivative (HpD) for 1 and 24 h, accumulated the aggregated porphyrin. The quantity of aggregated porphyrin was same in the plasma membrane and microsomes after isolating them from cells treated with HpD for 1 h whereas the microsomes accumulated higher quantity of aggregated porphyrin when cells were treated with HpD for 24 h. Photodynamic action of aggregated porphyrin on plasma membrane and microsomes was investigated using lipid specific fluorescent probes: 1,6-diphenyl-1,3,5-hexatrine (DPH) and 1-(4-trimethylammonium), 6-diphenyl-1,3,5-hexatrine(TMA-DPH). The time dependent anisotropy of these probes in the membranes was measured and the decay of anisotropy was analyzed using wobbling in cone model. Upon irradiation both the plasma membrane and the microsomes showed an increase in the limiting anis~)tropy and order parameter and a decrease in the cone angle of the lipid probes. The increase in the limiting anisotropy was pronounced in membranes isolated from the cells treated with HpD for 24 h. Photoinduced change in the limiting anisotropy was dependent on the duration of incubation of cells with HpD before isolating the membranes. In both the membranes. the membrane core was affected more as compared to the outer leaflet. In addition to the structural changes, a decrease in Na$^+$-K$^+$-ATPase and NADPH cyt c reductase activity was also observed upon irradiation of HpD treated cells. Inhibition in NADPH cyt c reductase was more when cells were treated with HpD for 24 h, however, Na$^+$-K$^+$-ATPase activity did not depend on the duration of the treatment of cells with HpD before irradiation. Our results suggest that the extent of photoinduced perturbations in the membranes varies as a function of duration of the treatment of cells with HpD and the membrane core is more susceptible to the photodynamic action of aggregated porphyrin.

• Molecules and Cells
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• v.40 no.5
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• pp.371-377
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• 2017

Despite the importance of the receptor activator of nuclear factor (NF)-kappaB ligand (RANKL)-RANK signaling mechanisms on osteoclast differentiation, little has been studied on how RANK expression is regulated or what regulates its expression during osteoclastogenesis. We show here that insulin signaling increases RANK expression, thus enhancing osteoclast differentiation by RANKL. Insulin stimulation induced RANK gene expression in time- and dose-dependent manners and insulin receptor shRNA completely abolished RANK expression induced by insulin in bone marrow-derived monocyte/macrophage cells (BMMs). Moreover, the addition of insulin in the presence of RANKL promoted RANK expression. The ability of insulin to regulate RANK expression depends on extracellular signal-regulated kinase 1/2 (ERK1/2) since only PD98059, an ERK1/2 inhibitor, specifically inhibited its expression by insulin. However, the RANK expression by RANKL was blocked by all three mitogen-activated protein (MAP) kinases inhibitors. The activation of RANK increased differentiation of BMMs into tartrate-resistant acid phosphatase-positive ($TRAP^+$) osteoclasts as well as the expression of dendritic cell-specific transmembrane protein (DC-STAMP) and d2 isoform of vacuolar ($H^+$) ATPase (v-ATPase) Vo domain (Atp6v0d2), genes critical for osteoclastic cell-cell fusion. Collectively, these results suggest that insulin induces RANK expression via ERK1/2, which contributes to the enhancement of osteoclast differentiation.

• International Journal of Oral Biology
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• v.38 no.1
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• pp.5-12
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• 2013

Recent studies indicate that reactive oxygen species (ROS) can act as modulators of neuronal activity, and are critically involved in persistent pain primarily through spinal mechanisms. In this study, we investigated the effects of NaOCl, a ROS donor, on neuronal excitability and the intracellular calcium concentration ($[Ca^{2+}]_i$) in spinal substantia gelatinosa (SG) neurons. In current clamp conditions, the application of NaOCl caused a membrane depolarization, which was inhibited by pretreatment with phenyl-N-tert-buthylnitrone (PBN), a ROS scavenger. The NaOCl-induced depolarization was not blocked however by pretreatment with dithiothreitol, a sulfhydryl-reducing agent. Confocal scanning laser microscopy was used to confirm whether NaOCl increases the intracellular ROS level. ROS-induced fluorescence intensity was found to be increased during perfusion of NaOCl after the loading of 2',7'-dichlorofluorescin diacetate ($H_2DCF$-DA). NaOCl-induced depolarization was not blocked by pretreatment with external $Ca^{2+}$ free solution or by the addition of nifedifine. However, when slices were pretreated with the $Ca^{2+}$ ATPase inhibitor thapsigargin, NaOCl failed to induce membrane depolarization. In a calcium imaging technique using the $Ca^{2+}$-sensitive fluorescence dye fura-2, the $[Ca^{2+}]_i$ was found to be increased by NaOCl. These results indicate that NaOCl activates the excitability of SG neurons via the modulation of the intracellular calcium concentration, and suggest that ROS induces nociception through a central sensitization.

• Korean Journal of Clinical Laboratory Science
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• v.41 no.2
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• pp.83-92
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• 2009

This study was undertaken to examine the effect of oxidants on membrane transport function in renal epithelial cells. Hydrogen peroxide ($H_2O_2$) was used as a model oxidant and the membrane transport function was evaluated by measuring $Na^+$-dependent phosphate ($Na^+$-Pi) uptake in opossum kidney (OK) cells. $H_2O_2$ inhibited $Na^+$-Pi uptake in a dose-dependent manner. The oxidant also caused loss of cell viability in a dose-dependent fashion. However, the extent of inhibition of the uptake was larger than that in cell viability. $H_2O_2$ inhibited $Na^+$-dependent uptake without any effect on $Na^+$-independent uptake. $H_2O_2$-induced inhibition of $Na^+$-Pi uptake was prevented completely by catalase, dimethylthiourea, and deferoxamine, suggesting involvement of hydroxyl radical generated by an iron-dependent mechanism. In contrast, antioxidants Trolox, N,N'-diphenyl-p-phenylenediamine, and butylated hydroxyanisole did not affect the $H_2O_2$ inhibition. Kinetic analysis indicated that $H_2O_2$ decreased Vmax of $Na^+$-Pi uptake with no change in the Km value. Phosphonoformic acid binding assay did not show any difference between control and $H_2O_2$-treated cells. $H_2O_2$ also did not cause degradation of $Na^+$-Pi transporter protein. Reduction in $Na^+$-Pi uptake by $H_2O_2$ was associated with ATP depletion and direct inhibition of $Na^+$-$K^+$-ATPase activity. These results indicate that the effect of $H_2O_2$ on membrane transport function in OK cells is associated with reduction in functional $Na^+$-pump activity. In addition, the inhibitory effect of $H_2O_2$ was not associated with lipid peroxidation.

• The Journal of Korean Medicine
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• v.21 no.3
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• pp.119-128
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• 2000

This study was carried out to determine if Salviae Radix extract (SRE) exerts protective effect against alterations in membrane transport function in rabbits with rhabdomyo lysis-induced acute renal failure. Acute renal failure was induced by intramuscular administration of glycerol (50%, 10 ml/kg). GFR in the glycerol-injected animals was reduced to 11% of the basal value and the fractional $Na^{+}$ excretion was increased to 7.8-fold, indicating generation of acute renal failure. When animals received SRE pretreatment for 7 days prior to glycerol injection, such changes were significantly attenuated. The fractional excretion of glucose and phosphate was increased more than 43-fold and 27-fold, respectively, in rabbits treated with glycerol alone. However, they were increased to 17-and 4.3-fold, respectively, in SRE-pretreated rabbits, and these values were significantly lower than those in rabbits treated with glycerol alone. Uptakes of glucose and phosphate in purified isolated brush-border membrane, the $Na^{+}-K^{+}-ATPase$ activity in microsomal fraction, and cellular ATP levels all were reduced in rabbits treated with glycerol alone. Such changes were prevented by SRE pretreatment. Uptakes of organic ions, PAH and TEA, in renal cortical slices were inhibited by the administration of glycerol, which was prevented by SRE pretreatment. Pretreatment of an antioxidant DPPD significantly attenuated the increase in the fractional excretion of glucose and phosphate induced by rhabdomyolysis. These results indicate that rhabdomyolysis causesimpairment inreabsorption of solutes in the proximal tubule via the generation of reactive oxygen species, and SRE pretreatment may provide the protection against the rhabdomyolysis-induced impairment by its antioxidant action.

• The Journal of Dong Guk Oriental Medicine
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• v.1
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• pp.55-80
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• 1992

In order to examine that the effect of Sam Hwa San, circulating the vital energy of Sam Cho and controlling body fluid metabolism, gives any influence on renal function, changes in the urine flow, eletrolytes excretion, plasma aldosterone concentration and renin activity were observed after intravenous infusion of the Sam Hwa San extract in rabbit. Also in vitro effect of the herb extract on oxygen consumption in renal cortical slices and ATPase activity in kidney microsomes was measured. The following results were obtained : 1. The urine flow was markedly increased at 10 min after intravenous infusion of the Sam Hwa San extract($0.134{\pm}0.015$ vs. $0.433{\pm}0.046ml/min.kg$), but return ed to normal value after 40 min of infusion. 2. The glomerular filtration rate was significantly increased at 10 min after in travenous infusion of the Sam Hwa San extract, and the renal plasma flow at 10 and 20 min after infusion of the Sam Hwa San extract, following return to normal value. 3. $Na^+$ excretion was significantly increased during 10-40 min after intravenous infusion of the Sam Hwa San extract, although showed the maximal rate at 10-20 min. The fractional $Na^+$ excretion was also increased during 10-40 min. $K^+$ excretion was rapidly increased at 10 min after the intravenous Infusion of the Sam Hwa San extract and then gradually decreased to normal level at 40 min. The fractional $K^+$ excretion was significantly increased during 10-40 min after the intravenous infusion of the Sam Hwa San extract. 4. The plasma aldosterone concentration and renin activity were not altered by the infusion of the Sam Hwa San extract. 5. The ouabain-sensitive oxygen consumption of renal cortical slices was significantly reduced by the Sam Hwa San extract(0.5 and 1.0 vol.%). 6. The Na-K-ATPase activity of renal microsomes was strongly inhibited by the Sam Hwa San extract(0.5 and 1.0 vol.%). These results suggest that the Sam Hwa San causes a strong diuretic effect which results from reduction of Na reabsorption in renal tubule by a direct inhibition of Na-pump and, in part, from all increase in renal blood flow. In clinic, it is considered to obtain the therapeutic effect in body fluid metabolism disharmony to cause the circular disorder of vital energy.

• YAKHAK HOEJI
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• v.24 no.1
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• pp.15-25
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• 1980

The investigation is concerned with the action of ginseng saponin on the contractile force in the rat heart and with the elucidation of the mechanism of the action. The effect of total ginseng saponin, ginsenoside Rb$_{1}$ of protopanaxadiol derivatives and ginsenoside Re of protopanaxatriol derivatives on the contractile force in isolated spontaneously beating normal rat heart was investigated. Total ginseng saponin was obtained from white ginseng by the method of Shibata and Namba. Ginsenoside Rb$_{1}$ and ginsenoside Re were isolated by the method of and Han, respectively. Total ginseng saponin exhibited a slight increase of the contractile force. Ginsenoside Rb$_{1}$ increased markedly the contractile force and dose dependent increase in contractile force was observed. However, ginsenoside Re did not increase the contractile force, but it prevented spontaneous decrease of the contractility of the heart. The mixture of the same dose of ginsenoside Rb$_{1}$ and Re showed a slight increase in the contractile force and its effect was similar to that obtained by total ginseng saponin. Pretreatment with propranolol abolished the positive inotropic effect of ginsenoside Rb$_{1}$ and the positive inotropic effect of ginsenoside Rb$_{1}$ was not observed in a reserpinized rat heart. Pretreatment with ginsenoside Re decreased or abolished the positive inotropic effect of epinephrine. Activities of Na+, K+ -ATPase were inhibited by ginsenoside Rb$_{1}$, total ginseng saponin and ginsenoside Re and these inhibitory effects were dose dependent. The results suggest that catecholamine release or inhibition of Na+, K+ -ATPase activities may be involved in the positive inotropic effect of gindenoside Rb$_{1}$. Ginsenoside Re counteracted the positive inotropic effect of ginsenoside Rb$_{1}$.