• The Korean Journal of Physiology and Pharmacology
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• v.16 no.2
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• pp.91-95
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• 2012

The role of the kidney in combating metabolic acidosis has been a subject of considerable interest for many years. The present study was aimed to determine whether there is an altered regulation of renal acid base transporters in acute and chronic acid loading. Male Sprague-Dawley rats were used. Metabolic acidosis was induced by administration of $NH_4Cl$ for 2 days (acute) and for 7days (chronic). The serum and urinary pH and bicarbonate were measured. The protein expression of renal acid base transporters [type 3 $Na^+/H^+$ exchanger (NHE3), type 1 $Na^+/{HCO_3}^-$ cotransporter (NBC1), Na-$K^+$ ATPase, $H^+$-ATPase, anion exchanger-1 (AE-1)] was measured by semiquantitative immunoblotting. Serum bicarbonate and pH were decreased in acute acid loading rats compared with controls. Accordingly, urinary pH decreased. The protein expression of NHE3, $H^+$-ATPase, AE-1 and NBC1 was not changed. In chronic acid loading rats, serum bicarbonate and pH were not changed, while urinary pH was decreased compared with controls. The protein expression of NHE3, $H^+$-ATPase was increased in the renal cortex of chronic acid loading rats. These results suggest that unaltered expression of acid transporters combined with acute acid loading may contribute to the development of acidosis. The subsequent increased expression of NHE3, $H^+$-ATPase in the kidney may play a role in promoting acid excretion in the later stage of acid loading, which counteract the development of metabolic acidosis.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.3
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• pp.187-191
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• 2003

$Na^+/H^+$ exchanger (NHE) has a critical role in regulation of intracellular pH (pHi) in the renal proximal tubular cells. It has recently been shown that dopamine inhibits NHE in the renal proximal tubules. Nevertheless, there is a dearth of information on the effects of long-term (chronic) dopamine treatment on NHE activities. This study was performed to elucidate the pHi regulatory mechanisms during the chronic dopamine treatments in renal proximal tubular OK cells. The resting pHi was greatly decreased by chronic dopamine treatments. The initial rate and the amplitude of intracellular acidification by isosmotical $Na^+$ removal from the bath medium in chronically dopamine-treated cells were much smaller than those in control. Although it seemed to be attenuated in $Na^+$-dependent pH regulation system, $Na^+$-dependent pHi recovery by NHE after intracelluar acid loading in the dopamine-treated groups was not significantly different from the control. The result is interpreted to be due to the balance between the stimulation effects of lower pHi on the NHE activity and counterbalance by dopamine. Our data strongly suggested that chronic dopamine treatment increased intrinsic intracellular buffer capacity, since higher buffer capacity was induced by lower resting pHi and this effect could attenuate pHi changes under extracellular $Na^+$-free conditions in chronically dopamine-treated cells. Our study also demonstrated that intracellular acidification induced by chronic dopamine treatments was not mediated by changes in NHE activity.

• Biomolecules & Therapeutics
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• v.25 no.6
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• pp.593-598
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• 2017

The $Na^+/H^+$ exchanger-1 (NHE-1) is a ubiquitously expressed pH-regulatory membrane protein that functions in the brain, heart, and other organs. It is increased by intracellular acidosis through the interaction of intracellular $H^+$ with an allosteric modifier site in the transport domain. In the previous study, we reported that glutamate-induced NHE-1 phosphorylation mediated by activation of protein kinase C-${\beta}$ (PKC-${\beta}$) in cultured neuron cells via extracellular signal-regulated kinases (ERK)/p90 ribosomal s6 kinases (p90RSK) pathway results in NHE-1 activation. However, whether glutamate stimulates NHE-1 activity solely by the allosteric mechanism remains elusive. Cultured primary cortical neuronal cells were subjected to intracellular acidosis by exposure to $100{\mu}M$ glutamate or 20 mM $NH_4Cl$. After the desired duration of intracellular acidosis, the phosphorylation and activation of PKC-${\beta}$, ERK1/2 and p90RSK were determined by Western blotting. We investigated whether the duration of intracellular acidosis is controlled by glutamate exposure time. The NHE-1 activation increased while intracellular acidosis sustained for >3 min. To determine if sustained intracellular acidosis induced NHE-1 phosphorylation, we examined phosphorylation of NHE-1 induced by intracellular acidosis by transient exposure to $NH_4Cl$. Sustained intracellular acidosis led to activation and phosphorylation of NHE-1. In addition, sustained intracellular acidosis also activated the PKC-${\beta}$, ERK1/2, and p90RSK in neuronal cells. We conclude that glutamate stimulates NHE-1 activity through sustained intracellular acidosis, which mediates NHE-1 phosphorylation regulated by PKC-${\beta}$/ERK1/2/p90RSK pathway in neuronal cells.

• Applied Chemistry for Engineering
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• v.10 no.6
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• pp.871-875
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• 1999

We calculated the characteristics of a phosphoric cation exchanger and studied on an accurately computable method to determine the ion exchange capacity for type of potentiometric titration curve. The ion exchanger was prepared by phosphorylation of a styrene-divinylbenzene copolymer with 4% crosslinking. The ion exchange capacity is 5.7 meq/g. The experimental pK values versus ${\mathit{x}}$ in phosphoric cation exchanger can be expressed as a linear equation. The ${\Delta}pK$ values were obtained from the slope of linear equation. The ${\Delta}pK$ values are the differences of antilogarithms(pK) values of the apparent equilibrium constant at complete and zeroth neutralization of the ion exchanger. Also the experimental pK values at ${\mathit{x}}=0.5$ were accorded well with theoretical data. And when it is titrated with NaOH and $Ba(OH)_2$ solutions, a good agreement between experimental and theoretical pK values for various ${\mathit{x}}$ was seen in all the potentiometric titration curves. We knew that the inflection point of potentiometric titration curve in the case of divalent ions are changed much large than that for monovalent ions. If the relation between g values and ${\partial}pH/{\partial}g$ was plotted to the Lorentz distribution curve, ion exchange capacity can be accurately evaluated.

• Biomolecules & Therapeutics
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• v.19 no.4
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• pp.445-450
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• 2011

Preciously, we demonstrated that a novel NHE-1 inhibitor, KR-33028 attenuated cortical neuronal apoptosis induced by glutamate. In the present study, we investigated the signaling mechanism of neuroprotective effect of KR-33028 against glutamate-induced neuronal apoptosis, especially focusing on mitochondrial death pathway. Our data showed that glutamate induces a biphasic rise in mitochondrial $Ca^{2+}$ and that KR-33028 significantly prevents the second phase increase, but not the first phase increase in mitochondrial $Ca^{2+}$. Furthermore, KR-33028 restored the ${\Delta}{\Psi}_m$ dissipation and cytochrome c release into cytoplasm induced by glutamate in a concentration-dependent manner. The inhibition of mitochondrial $Ca^{2+}$ overload by ruthenium red also inhibited glutamate-induced apoptotic cell death, mitochondrial membrane potential, ${\Delta}{\Psi}_m$ dissipation and cytochrome c release. These data suggest that inhibition of mitochondrial $Ca^{2+}$ overload is likely to be attributable to anti-apoptotic effect of KR-33028. Taken together, our results suggest that anti-apoptotic effects of NHE-1 inhibitor, KR-33028 may be mediated through maintenance of mitochondrial function.

• 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.

• Biomolecules & Therapeutics
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• v.14 no.2
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• pp.110-113
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• 2006

We tested effect of sarcotride A, a bioactive cyclitol derivative from a marine sponge, on membrane potential in C6 glioma cells. Membrane potential was estimated by measuring fluorescence change of DiBAC-loaded glioma cells. Sarcotride A increased membrane potential in a concentration-dependent manner. We tested effects of pertussis toxin, U73122, EIPA, and $Na^+-free$ media on sarcotride A-induced increase of membrane potential to investigate involvement of G proteins, phospholipase C, $Na^+/H^+$ exchanger, and $Na^+$ channels. However, we were not able to observe any significant effect of those pharmacological inhibitors, excluding the involvement of the molecules as candidate targets or signaling molecules of sarcotride A-induced increase of membrane potential. Further investigation is necessary to elucidate action mechanism of sarcotride A.

• Journal of the Korean Chemical Society
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• v.34 no.6
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• pp.582-592
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• 1990

Retention behavior of lanthanide-$\alpha$HiBA complexes was studied on the cation exchanger (LC-18 coated with $C_{20}H_{41}SO_4^-$). An equation predicting retention of lanthanides in isocratic or gradient elution with sodium ion and $\alpha$-HiBA concentration was derived from ion exchange equilibria of metal-ligand complex system, respectively. The relations between log k' and log [Na$^+$] /log [$\alpha$-HiBA) showed non-linearity in isocratic elution. In gradient elution a good linearity between log k' vs log R was obtained. The values of slopes (log k / log R) gave good agreements between calculation and experiment. Individual capacity factors ($k'_{Ln}^{3+}, k'_{LnL}^{2+}, k'{LnL2+}) and stability constant (${\beta}_1$, ${\beta}_2$, ${\beta}_3$) of lanthanide-$\alpha$HiBA complexes were calculated by the non-linear least square fittings using the retention equation. The correlation coefficients of lanthanides were shown better than 0.9996 between experiment and calculation.

• Journal of the Korean Chemical Society
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• v.15 no.2
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• pp.49-54
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• 1971

It is shown that the impurities of Cu(II), Pb(II), Zn(II) and Ag(I) in Bismuth metal and the components of Pb(II), Zn(II) and Sn(IV) in Bismuth alloy are separated into their components from each other by elutions through $3.14cm^2{\times}10cm$ cation exchange resin, $Dowex\;50w\;{\times}\;8$ (100~200 mesh), column with the mixed solutions of HAc and NaAc as the eluents. The elution curve of Fe(III) has a long tailing and is not separated quantitatively from Bi(III). The eluents used for this separation are as follows; 1M HAc + 0.1M NaAc (pH 3.36) for Fe(III) and Bi (III). 0.3M HAc + 0.3M NaAc (pH 4.70) for Cu(II), Pb(II) and Zn(II). 0.5M HAc + 0.5M NaAc (pH4.70) for Ag(I) and Sn(IV). The analysis of cations eluted are carried out by spectrophotometry and EDTA titrimetry. Their recoveries are more than 99%.

• BMB Reports
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• v.47 no.7
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• pp.393-398
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• 2014

The role of Bax inhibitor-1 (BI-1) in the protective mechanism against apoptotic stimuli has been studied; however, as little is known about its role in death receptor-mediated cell death, this study was designed to investigate the effect of BI-1 on Fas-induced cell death, and the underlying mechanisms. HT1080 adenocarcinoma cells were cultured in high concentration of glucose media and transfected with vector alone (Neo cells) or BI-1-vector (BI-1 cells), and treated with Fas. In cell viability, apoptosis, and caspase-3 analyses, the BI-1 cells showed enhanced sensitivity to Fas. Fas significantly decreased cytosolic pH in BI-1 cells, compared with Neo cells, and this decrease correlated with BI-1 oligomerization, mitochondrial $Ca^{2+}$ accumulation, and significant inhibition of sodium-hydrogen exchanger (NHE) activity. Compared with Neo cells, a single treatment of BI-1 cells with the NHE inhibitor EIPA or siRNA against NHE significantly increased cell death, which suggests that the viability of BI-1 cells is affected by the maintenance of intracellular pH homeostasis through NHE.