• Animal cells and systems
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• v.13 no.3
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• pp.283-288
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• 2009

The ubiquitous plasma membrane $Na^+/H^+$ exchanger 1 (NHE1) is rapidly activated in response to various extracellular stimuli and maintains normal cytoplasmic pH. Yeast two-hybrid screening was used in order to identify proteins interacting with NHE1 using its cytoplasmic domain as a bait from HeLa cDNA library. One of the interacting cDNA clones was human Lactate dehydrogenase B (LDHB). In vitro translated LDHB was pulled down together with GST-NHE1.cd protein in the GST pull down assay, confirming the interaction in vitro. LDHB antibody immunoprecipitated endogenous LDHB together with NHE1 from H9c2 cells, validating cellular interaction between NHE1 and LDHB. Subsequent analysis revealed that the overexpression of LDHB increased intracellular PH, implying opening of the NHE1 transporter. Moreover, overexpression of LDHB activated caspase 3 and induced cell death, consistent with the expected phenotype of hyper-activation of NHE1. Collectively, our data indicate that LDHB modulates NHE1 activity via physical interaction.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.3
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• pp.269-275
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• 2018

$Na^+/H^+$ exchangers (NHEs) have been shown to be involved in regulating cell volume and maintaining fluid and electrolyte homeostasis. Pooled evidences have suggested that loss of $Na^+/H^+$ exchanger isoform 8 (NHE8) impairs intestinal mucosa. Whether NHE8 participates in the pathology of infectious colitis is still unknown. Our previous study demonstrated that somatostatin (SST) could stimulate the expression of intestinal NHE8 so as to facilitate $Na^+$ absorption under normal condition. This study further explored whether NHE8 participates in the pathological processes of infectious colitis and the effects of SST on intestinal NHE8 expression in the setting of infectious colitis. Our data showed that NHE8 expression was reduced in Citrobacter rodentium (CR) infected mice. Up-regulation of NHE8 improved diarrhea symptom and mucosal damage induced by CR. In vitro, a similar observation was also seen in Enteropathogenic E. coli (EPEC) infected Caco-2 cells. Seglitide, a SST receptor (SSTR) 2 agonist, partly reversed the inhibiting action of EPEC on NHE8 expression, but SSTR5 agonist (L-817,818) had no effect on the expression of NHE8. Moreover, SST blocked the phosphorylation of p38 in EPEC-infected Caco-2 cells. Taken together, these results suggest that enhancement of intestinal NHE8 expression by SST could ameliorate the symptoms of mice with infectious colitis.

• Journal of Food Hygiene and Safety
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• v.30 no.3
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• pp.242-248
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• 2015

This study was performed to investigate the microbiological contamination on toothbrushes, toothbrush caps, and tooth cleaning cups in the child care centers and to evaluate the toxin genes, toxin production ability and antibiotic resistance of food-borne pathogens. The average number of total aerobic bacteria and fungi were 5.3 log CFU and 3.2 log CFU. Coliform bacteria were detected in 41 (54.7%) of 75 toothbrushes, 13 (44.8%) of 29 toothbrush caps, and 29 (44.6%) of 65 tooth cleaning cups. Salmonella spp. was not detected in all of samples but Bacillus cereus was isolated from 1 (1.3%) of 75 toothbrushes and 2 (3.1%) of 65 tooth cleaning cups. Staphylococcus aureus was detected in 1 (1.5%) of 65 tooth cleaning cups. The nheA, nheB, nheC, hblC, hblD, hblA and entFM toxin genes were possessed in B. cereus isolated from toothbrush which also produce NHE and HBL enterotoxins. S. aureus was resistant to ampicillin and penicillin, while B. cereus was resistant to ${\beta}-lactam$ antibiotics. These results indicated that the sanitary conditions of toothbrushes and tooth cleaning cups in the child care centers should be improved promptly. The UV sterilization after drying and then storage in dried condition is required to improve the sanitary condition of toothbrushes and tooth cleaning cups in the child care center.

• Health Policy and Management
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• v.12 no.3
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• pp.99-111
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• 2002

This paper draws the determinants of National Health Expenditures(min) and collectivizes OECD countries which are positioned by same conditions using the decision tree analysis. Major findings are summarized as follows. We find that the power of influence of income level on NHE has been 58.35% in 1985, 65.37% in 1990, 66.90% in 1995, and 66.47% in 1997. The power of influence of public share in NHE has been on the increase during that period: 19.50% in 1985, 19.91% in 1990, 22.81% in 1995 and 26.88% in 1997. The two factors(income level, public share) tells for the most part of NHE: 77.85% in 1985, 85.28% in 1990, 89.71% in 1995, 93.35% in 1997. Our results support the hypothesis that NHE could be explained mostly by the income level and show that public share is negatively correlated with the growth of NHE.

• 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.

• 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.

• Health Policy and Management
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• v.4 no.2
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• pp.77-110
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• 1994

This study is an empiriacl analysis of effects of government intervention on the health care delivery system in Korea. The purposes of this study are to find out the effects of government intervention on the per capita national health expenditure(per capita NHE), crude mortality rate(CMR), and institutional efficiency. Here, the institutional efficiency is defined as a formula shown below: log$\frac{100-curde mortality rate }{per capita NHE}$$\times$100. The formula indicates that the instiutional efficiency increases if the CMR and/or per capita NHE goes down. In the meantime the government intervention is measured by six independent variables: I) the degree of social developments, ii) the numberr of physicians per 100, 000 population, iii) the proportion of specialists among the total physicians, iv) the proportion of public expenditure among the NHE, v) the proportion of public beds to the total number of beds, vi) the proportion of physicians working at the public sector to the total number of physicians. In the above six independent variables iv), v) and vi) are the ones that reflect the degree of government intervention. In actual calculation, the two independent variables v) and vi) are integrated into a new variable based on one to one correspondence. The materials used are the time-series data from 1970 through 1990 in Korea. A path analysis and the time-series regression analysis were adopted to estimate and examine the causal relationship between variables involved. And decomposition of the effect of causal relationship is made to find net effect, direct and indirect effect. The major findings are as follows; 1. The effect of public expenditure, number of physicians per 100, 000 population, the proportion of specialists among the total physicians and social development shows a positive relationship with per capita NHE. Only if the government intervention would be counted, the effects of the number of physicians and the proportion of specialists succeed in containing per capita NHE. 2. In additionn to the above four variables, one additional variable, per capita NHE, was also responsible for the reduction of CMR. The factor of social development found to be the most potent predictor of the CMR reduction. However, the CMR reduction due to government intervention was negligible. 3. Meanwhile, the above four variables were found to was have negative effects on the institutional efficiency. The reverse is true when the government intervention is counted. For example, the number of physicians and the proportion of specialists have played a positive role in raising institutional efficiency via goverment intervention. This comes from the factual effect that the increment of institutional efficiency via the reduction of per capita NHE is bigger than via the reduction of CMR.

• 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.

• Korean Journal of Food Science and Technology
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• v.46 no.3
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• pp.334-340
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• 2014

Toxin-producing Bacillus cereus is the causative agent of two different types of food poisoning: the emetic and the diarrheal types. This study was conducted to investigate the presence of enterotoxin and emetic toxin genes in 263 B. cereus isolated from 619 different ready-to-eat food items. Hemolytic enterotoxins hblA, hblC, and hblD were detected in 85.6, 41.1, and 76.8%, respectively, of the B. cereus isolates. About 67.0% (175/263) of the isolates presented all of three genes. Non-hemolytic enterotoxins nheA, nheB, and nheC were detected in 100, 97.0, and 68.4% of the isolates, respectively. Approximately 90.0% (236/263) of the isolates presented all of these three non-hemolytic enterotoxin genes. Emetic toxin gene, CER, was detected in 132 of 263 (50.2%) isolates. Computer-assisted cluster analysis of Rep-PCR profiles showed a high genetic diversity among the isolates. All B. cereus isolates from food samples tested in this study carried at least 6 of 10 toxin genes.

• YAKHAK HOEJI
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• v.55 no.3
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• pp.247-250
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• 2011

An increase in ventricular pressure can alter cardiac excitation and contraction. Recent report has demonstrated that fluid pressure (FP) suppresses L-type $Ca^{2+}$ current with acceleration of the current inactivation in ventricular myocytes. Since the L-type $Ca^{2+}$ channels known to be regulated by intracellular pH ($pH_i$), this study was designed to explore whether pressurized fluid flow affects pHi in isolated rat ventricular myocytes. A flow of pressurized (~16 dyne/$cm^2$) fluid, identical to that bathing the myocytes, was applied onto single myocytes, and intracellular $H^+$ concentration was monitored using confocal $H^+$ imaging. FP significantly decreased $pH_i$ by $0.07{\pm}0.01$ pH units (n=16, P<0.01). Intracellular acidosis enhances the activity of $Na^+-H^+$ exchanger (NHE). Therefore, we examined if the NHE activity is increased by FP using the NHE inhibitor, HOE642. Although HOE642 did not alter $pH_i$ in control conditions, it decreased $pH_i$ in cells pre-exposed to FP, suggesting enhancement of NHE activity by FP. In addition, FP-induced intracellular acidosis was larger in cells pre-treated with HOE642 than in cells under the control conditions. These results suggest that FP induces intracellular acidosis and that NHE may contribute to extrude $H^+$ during the FP-induced acidosis in rat ventricular myocytes.