• BMB Reports
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• v.47 no.10
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• pp.563-568
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• 2014

Human genome projects have enabled whole genome mapping and improved our understanding of the genes in humans. However, many unknown genes remain to be functionally characterized. In this study, we characterized human chromosome 4 open reading frame 34 gene (hC4orf34). hC4orf34 was highly conserved from invertebrate to mammalian cells and ubiquitously expressed in the organs of mice, including the heart and brain. Interestingly, hC4orf34 is a novel ER-resident, type I transmembrane protein. Mutant analysis showed that the transmembrane domain (TMD) of hC4orf34 was involved in ER retention. Overall, our results indicate that hC4orf34 is an ER-resident type I transmembrane protein, and might play a role in ER functions including $Ca^{2+}$ homeostasis and ER stress.

• Journal of Ginseng Research
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• v.31 no.3
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• pp.117-126
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• 2007

Ginseng, the root of Panax species, a well-known herbal medicine has been used as a traditional medicine for thousands of years and is now a popular and worldwide used natural medicine. Ginseng has been used primarily as a tonic to invigorate weak bodies to help the restoration of homeostasis in a wide range of pathological conditions such as cardiovascular diseases, cancer, immune deficiency and hepatotoxicity. Although conclusive clinical data in humans is still missing, recent research results have suggested that some of the active ingredients ginseng exert beneficial effects on central nervous system (CNS) disorders and neurodegenerative diseases, suggesting it could be used in treatment of psychotic disorders. Data from neural cell cultures and animal studies contribute to the understanding of these mechanisms that involve inhibitory effects on stress-induced corticosterone level increasing and modulating of neurontransmitters, reducing $Ca^{2+}$ over-influx, scavenging of free radicals and counteracting excitotoxicity. In this review, we focused on recently reported medicinal effects of ginseng and summarized the possibility of its applications on psychotic disorders.

• Biomedical Science Letters
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• v.22 no.3
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• pp.107-114
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• 2016

Maintenance of fasting blood glucose levels is important for glucose homeostasis. Disruption of feedback mechanisms are a major reason for elevations of glucose level in blood, which is a risk factor for type 2 diabetes mellitus that is mainly caused by malfunction of pancreatic beta-cell and insulin. The fasting blood glucose level has been known to be influenced by genetic and environmental factors. Mitochondria have many functions for cell survival and death: glucose metabolism, fatty acid oxidation, ATP generation, reactive oxygen species (ROS) metabolism, calcium handling, and apoptosis regulation. In addition to these functions, mitochondria change their morphology dynamically in response to multiple signals resulting in fusion and fission. In this study, we aimed to examine association between fasting blood glucose levels and variants of the genes that are reported to have functions in mitochondrial dynamics, fusion and fission, using a cohort study. A total 416 SNPs from 36 mitochondrial dynamics genes were selected to analyze the quantitative association with fasting glucose level. Among the 416 SNPs, 4 SNPs of PRKACB, 13 SNPs of PPP3CA, 6 SNPs of PARK2, and 3 SNPs of GDAP1 were significantly associated. In this study, we were able to confirm an association of mitochondrial dynamics genes with glucose levels. To our knowledge our study is the first to identify specific SNPs related to fasting blood glucose level.

• 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.

• Biomolecules & Therapeutics
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• v.20 no.5
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• pp.463-469
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• 2012

Atopic dermatitis is a chronic, inflammatory disease of the skin with increased transepidermal water loss. Both an abnormal inflammatory response and a defective skin barrier are known to be involved in the pathogenesis of atopic dermatitis. Protease activated receptor 2 (PAR2) belongs to a family of G-protein coupled receptors and is activated by both trypsin and a specific agonist peptide, SLIGKV-$NH_2$. PAR2 is expressed in suprabasal layers of the epidermis and regulates inflammatory responses and barrier homeostasis. In this study, we show that nordihydroguaiaretic acid (NDGA) inhibits the PAR2-mediated signal pathway and plays a role in skin barrier recovery in atopic dermatitis. Specifically, NDGA reduces the mobilization of intracellular $Ca^{2+}$ in HaCaT keratinocytes by down-regulating inflammatory mediators, such as interleukin-8, thymus and activation-regulated chemokine and intercellular cell adhesion molecule-1 in HaCaT keratinocytes. Also, NDGA decreases the protein expression of involucrin, a differentiation maker of keratinocyte, in both HaCaT keratinocytes and normal human epidermal keratinocytes. We examined NDGA-recovered skin barrier in atopic dermatitis by using an oxazolone-induced atopic dermatitis model in hairless mice. Topical application of NDGA produced an increase in transepidermal water loss recovery and a decrease in serum IgE level, without weight loss. Accordingly, we suggest that NDGA acts as a PAR2 antagonist and may be a possible therapeutic agent for atopic dermatitis.

• Animal Bioscience
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• v.36 no.5
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• pp.740-752
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• 2023

Objective: Dietary phytase increases bioavailability of phytate-bound phosphorus (P) in pig nutrition affecting dietary calcium (Ca) to P ratio, intestinal uptake, and systemic utilization of both minerals, which may contribute to improper bone mineralization. We used phytase to assess long-term effects of two dietary available P (aP) levels using a one-phase feeding system on gene expression related to Ca and P homeostasis along the intestinal tract and in the kidney, short-chain fatty acids in stomach, cecum, and colon, serum, and bone parameters in growing gilts and barrows. Methods: Growing pigs (37.9±6.2 kg) had either free access to a diet without (Con; 75 gilts and 69 barrows) or with phytase (650 phytase units; n = 72/diet) for 56 days. Samples of blood, duodenal, jejunal, ileal, cecal, and colonic mucosa and digesta, kidney, and metacarpal bones were collected from 24 pigs (6 gilts and 6 barrows per diet). Results: Phytase decreased daily feed intake and average daily gain, whereas aP intake increased with phytase versus Con diet (p<0.05). Gilts had higher colonic expression of TRPV5, CDH1, CLDN4, ZO1, and OCLN and renal expression of TRPV5 and SLC34A3 compared to barrows (p<0.05). Phytase increased duodenal expression of TRPV5, TRPV6, CALB1, PMCA1b, CDH1, CLDN4, ZO1, and OCLN compared to Con diet (p<0.05). Furthermore, phytase increased expression of SCL34A2 in cecum and of FGF23 and CLDN4 in colon compared to Con diet (p<0.05). Alongside, phytase decreased gastric propionate, cecal valerate, and colonic caproate versus Con diet (p<0.05). Phytase reduced cortical wall thickness and index of metacarpal bones (p<0.05). Conclusion: Gene expression results suggested an intestinal adaptation to increased dietary aP amount by increasing duodenal trans- and paracellular Ca absorption to balance the systemically available Ca and P levels, whereas no adaption of relevant gene expression in kidney occurred. Greater average daily gain in barrows related to higher feed intake.

• Journal of Ginseng Research
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• v.42 no.2
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• pp.165-174
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• 2018

Background: Extended endoplasmic reticulum (ER) stress may initiate apoptotic pathways in cancer cells, and ER stress has been reported to possibly increase tumor death in cancer therapy. We previously reported that caspase-8 played an important role in compound K-induced apoptosis via activation of caspase-3 directly or indirectly through Bid cleavage, cytochrome c release, and caspase-9 activation in HL-60 human leukemia cells. The mechanisms leading to apoptosis in A549 and SK-MES-1 human lung cancer cells and the role of ER stress have not yet been understood. Methods: The apoptotic effects of compound K were analyzed using flow cytometry, and the changes in protein levels were determined using Western blot analysis. The intracellular calcium levels were monitored by staining with Fura-2/AM and Fluo-3/AM. Results: Compound K-induced ER stress was confirmed through increased phosphorylation of $eIF2{\alpha}$ and protein levels of GRP78/BiP, XBP-1S, and $IRE1{\alpha}$ in human lung cancer cells. Moreover, compound-K led to the accumulation of intracellular calcium and an increase in m-calpain activities that were both significantly inhibited by pretreatment either with BAPTA-AM (an intracellular $Ca^{2+}$ chelator) or dantrolene (an RyR channel antagonist). These results were correlated with the outcome that compound K induced ER stress-related apoptosis through caspase-12, as z-ATAD-fmk (a specific inhibitor of caspase-12) partially ameliorated this effect. Interestingly, 4-PBA (ER stress inhibitor) dramatically improved the compound K-induced apoptosis. Conclusion: Cell survival and intracellular $Ca^{2+}$ homeostasis during ER stress in human lung cancer cells are important factors in the induction of the compound K-induced apoptotic pathway.

• Korean Journal of Poultry Science
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• v.44 no.1
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• pp.19-28
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• 2017

The eggshell is an intricate and highly ordered structure composed of multiple layers and a calcified matrix. The eggshell is formed at the uterine segment of the chicken oviduct. In this study, histological changes in the uterine endometrium and the expression of the eggshell-related genes were investigated according to hen age. We analyzed the expression of eggshell protein-related genes, such as OCX-32, OCX-36, OC-17, OC-116, and eggshell-ion-related genes, such as CABL-1, SPP1, SCNN1G, ATP2A2, CA2, and CALM1. In chicken uterine endometrium, histological deformation, fibrosis, atrophy and elimination of micro-villi were found with increasing hen age. The concentration of blood-ion components did not significantly change with age. The amount of telomeric DNA in uterine endometrial cells decreased with increasing hen age. The expression of most of the eggshell-related genes changed significantly with increasing hen age. The expression of some ovo-proteins, which play a role in eggshell formation, increased with increasing hen age; however, there were no significant correlations among eggshell protein genes. Eggshell ion-related genes, such as ATP2A2, SCNN1G, CA2, and CALM1, were closely related to each other. The OCX-32 and OCX-36 genes were closely related to some of the eggshell ion genes. Eggshell protein-related genes, such as the OCX-32, OCX-36 genes and ion-related genes such as CALB-1, ATP2A2, SCNN1G, CA2, CALM1, affected eggshell formation, mutually or independently. This study shows that, uterine although endometrial cell damage occurs with increasing hen age, normal eggshells can be formed in old hens. This suggests that eggshell protein-and eggshell ion-related genes also control the homeostasis of eggshell formation.

• Asian-Australasian Journal of Animal Sciences
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• v.25 no.5
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• pp.701-707
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• 2012

Immune stress is the loss of immune homeostasis caused by external forces. The purpose of this experiment was to investigate the effects of immune stress on the growth performance, small intestinal enzymes and peristalsis rate, and mRNA expression of nutrient transporters in broiler chickens. Four hundred and thirty-two 1-d-old broilers (Cobb500) were randomly assigned to four groups for treatment; each group included nine cages with 12 birds per cage. Group 1 = no vaccine (NV); Group 2 = conventional vaccine (CV); group 3 = lipopolysaccharide (LPS)+conventional vaccine (LPS); group 4 = cyclophosphamide (CYP)+conventional vaccine (CYP). The results demonstrated that immune stress by LPS and CYP reduced body weight gain (BWG), feed intake (FI), small intestine peristalsis rate and sIgA content in small intestinal digesta (p<0.05). However, the feed conversion ratio (FCR) remained unchanged during the feeding period. LPS and CYP increased intestinal enzyme activity, relative expression of SGLT-1, CaBP-D28k and L-FABP mRNAs (p<0.05). LPS and CYP injection had a negative effect on the growth performance of healthy broiler chickens. The present study demonstrated that NV and CV could improve growth performance while enzyme activity in small intestine and relative expression of nutrient transporter mRNA of NV and CV were decreased in the conditions of a controlled rational feeding environment. It is generally recommended that broilers only need to be vaccinated for the diseases to which they might be exposed.

• Korean Journal of Veterinary Research
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• v.50 no.2
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• pp.85-91
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• 2010

The large amount of tissue culture medium (TCM), which contains some of the active secretory components of Korean wild ginseng (KWG; Panax ginseng) such as saponins, is usually discarded after harvest of KWG. The present study was aimed to investigate the efficacy of oral administration of the TCM-KWG on growth performance and diseases resistance in broiler chickens. A day old broiler chickens randomized in 6 groups (n = 60/groups) were administered orally with 0, 2, 4, 8, 16 and 32 mL/L TCMKWG through drinking water for 5 weeks and examined the change of weight gain, feed intake and blood components. Also, five weeks old broiler chickens (n = 15/groups) were challenged orally with Salmonella (S.) gallinarum and investigated the mortality in broiler chickens. An average weight gain and feed intake significantly didn't change in TCM-KWG administration groups as compared to control group. The concentration of calcium (Ca), phosphate (Pi) and potassium (K) in serum were increase by TCM-KWG administration in broiler chickens. We also found that oral administration of TCM-KWG through drinking water significantly reduced the mortality in broiler chickens experimentally infected with virulent S. gallinarum. The results of this study indicated that TCM-KWG administration may elevate the resistance on disease and improved the skeleton formation and body homeostasis of chickens, and TCM-KWG can be used as a cost-effective and environmentally alternative additives to control of the disease and growth.