• Journal of Nutrition and Health
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• 제34권3호
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• pp.271-284
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• 2001

This study was performed to investigate the effects of dried powders and water extracts of Paecilomyces tenuipes(P. tenuipes) and Cordyceps militaris(C. militaris) on lipid metabolism, lipid peroxidation and antioxidative capacity and immune status in rats. Thirty-five male Sprague-Dawley rats weighting 195$\pm$21g were grouped into five according to body weight. Ratw were raised for four weeks with diet containing either 4%, 2%(w/w) of dried P. tenuipes powders(TP-4, TP-2) or water extracts from equal amounts of each 4% P. tenuipes and C. militaris powder(TE-4, ME-4). Food intake, weight gain of all groups were not significantly different from those of control group. Lipid metabolism in general was not significantly different among all the groups. However both dried P. tenuipes powder lowered plasma cholesterol level slightly, water extract groups showed tendency of higher plasma HDL-cholesterol and lower liver cholesterol levels than control. Plasma and liver thiobarbituric acid reactive substance(TBARS) concentrations of all the experimental groups were lower than control group. Red blood cell(RBC) and liver superoxide dismutase(SOD) activities were not generally different among all groups. Liver xanthine oxidase(XOD) activities of all groups were tended to be lower than control group. Proliferation of aplenocytes induced by mitogens, concanavalin A and lipopolysaccharide, were increased in TP-2 group. The TP-4 group showed increased CD8 T cells and MHC class II expression without changes in CD4 T cells, B cells and G/M ratio, suggesting activated cytotoxic T cell activity in vivo. Increase of G/M ratio but not of MHC class II in TP-2 group indicated the possible acute inflammatory reaction by the ingested substances in gastrointestinal tract. ME-4 group showed enhanced cellular immunity without vigorous changes of immune parameters in brief periods. In conclusion, both P. tenuipes and C. militaris stimulated antioxidant capacity and immune status in rats. Among groups, water extract of C. militaris was most effective in both capacities, though dried powder of P. tenuipes at 2% dietary level was more effective in antioxidant activity, as various results by different strains were observed.(Korean J Nutrition 34(3) : 271~284, 2001)

• Molecules and Cells
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• 제40권2호
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• pp.123-132
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• 2017

Insulin signaling is coordinated by insulin receptor substrates (IRSs). Many insulin responses, especially for blood glucose metabolism, are mediated primarily through Irs-1 and Irs-2. Irs-1 knockout mice show growth retardation and insulin signaling defects, which can be compensated by other IRSs in vivo; however, the underlying mechanism is not clear. Here, we presented an Irs-1 truncated mutated mouse ($Irs-1^{-/-}$) with growth retardation and subcutaneous adipocyte atrophy. $Irs-1^{-/-}$ mice exhibited mild insulin resistance, as demonstrated by the insulin tolerance test. Phosphatidylinositol 3-kinase (PI3K) activity and phosphorylated Protein Kinase B (PKB/AKT) expression were elevated in liver, skeletal muscle, and subcutaneous adipocytes in Irs-1 deficiency. In addition, the expression of IRS-2 and its phosphorylated version were clearly elevated in liver and skeletal muscle. With miRNA microarray analysis, we found miR-33 was down-regulated in bone marrow stromal cells (BMSCs) of $Irs-1^{-/-}$ mice, while its target gene Irs-2 was up-regulated in vitro studies. In addition, miR-33 was down-regulated in the presence of Irs-1 and which was up-regulated in fasting status. What's more, miR-33 restored its expression in re-feeding status. Meanwhile, miR-33 levels decreased and Irs-2 levels increased in liver, skeletal muscle, and subcutaneous adipocytes of $Irs-1^{-/-}$ mice. In primary cultured liver cells transfected with an miR-33 inhibitor, the expression of IRS-2, PI3K, and phosphorylated-AKT (p-AKT) increased while the opposite results were observed in the presence of an miR-33 mimic. Therefore, decreased miR-33 levels can up-regulate IRS-2 expression, which appears to compensate for the defects of the insulin signaling pathway in Irs-1 deficient mice.

• 대한한의학방제학회지
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• 제21권1호
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• pp.99-110
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• 2013

Objectives : This study was designed to investigate the effect of a herbal preparation HJ01 consisting of Salicornia herbacea, Citri Reticulatae Pericarpium, Crataegi Fructus and Glycyrrhizae Radix on adipocyte differentiation in OP9 cells and on poloxamer 407(P-407)-induced hyperlipidemia in mice. Methods : 1. MTT assay was used to evaluate the potential cytotoxicity of Salicornia herbacea, Citri Reticulatae Pericarpium, Crataegi Fructus, Glycyrrhizae Radix and HJ01, respectively. 2. Bone-marrow derived OP9 cells were treated with HJ01, and the alterations in fat storage in the cells were determined by the Oil red O assay. 3. The protein level of CAAAT/enhancer binding protein alpha($C/EBP{\alpha}$), as a adipocyte differentiation marker, was examined using western blot analysis in differentiated OP6 cells. 4. Adult male C57BL6 mice received intraperitoneal injections of P407 to induce hyperlipidemia, simultaneously, were treated with HJ01 for 4 weeks. Then the cholesterol (TC), triglyceride (TG) and high-density lipoprotein-cholesterol (HDL-c) levels in sera and liver tissues were measured. Results : 1. The MTT assay exhibited that Salicornia herbacea, Citri Reticulatae Pericarpium, Crataegi Fructus, Glycyrrhizae Radix and HJ01 showed no significant cytotoxicity in tested dosages. 2. Ten days' treatment with HJ01 markedly inhibited the increases in fat storage in differentiated OP6 cells. 3. Four weeks' treatment with HJ01 down-regulated the protein level of CAAAT/enhancer binding protein alpha($C/EBP{\alpha}$) but up-regulated the levels of adiponectin in differentiated OP9 cells. 5. HJ01 inhibited the accumulation of TC and TG in liver tissues and increased serum levels of TC in hyperlipidemic mice. Conclusions : These results suggest that HJ01 can in vitro inhibit adipocyte differentiation and fat storage in OP6 cells, in vivo improve the hyperlipidemia induced by P-407 in mice, which may be mediated by promoting glucose uptake and improving a lipid metabolite profile.

• 한국어병학회지
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• 제30권2호
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• pp.115-134
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• 2017

A total number of 668 apparently healthy fish were obtained from farm to study the effect of two heavy metals (Copper and Mercury) on histopathology of liver, kidney, spleen, gills and muscles also residues in muscles. The $LC_{50}$/96 hr. of Cu and Hg were estimated and fish exposed to 1/2 $LC_{50}$ for 7 days and for 1/10 $LC_{50}$ for 8 weeks from each product separately. Histopathological findings in acute and chronic mercuric chloride toxicity revealed degeneration and necrosis in the glomeruli, interstitium tissue and epithelium lining renal tubules. The tubular epithelium became necrotic at several places. Eosinophilic hyaline droplets is exist in the cytoplasm of the necrosed cells. Degenerative changes and hyperactivity in melanomachrophage center was seen in the spleen together with some necrotic areas. Necrosis and aggregation of melanomachrophage were seen in the hepatic cells, Hepatic cells showed vacuolar degeneration in the hepatic cells. Gills showed loss in the lamellae of the filaments associated with edema, inflammatory cells infiltration and haemorrhages in the arch. The sarcoplasm of the bundles of the skeletal muscle showed granular degeneration and focal inflammatory cells infiltration between the hyalinized bundles. Mercury residues obtained from these studies in the acute toxicity were 0.22 ppm/gm in the 2nd day, 0.411 ppm/gm in the $5^{th}$ day ended with 0.96 ppm/gm in the $7^{th}$ day. In chronic toxicity it was 1.1320, 1.7140, 2.3620 and 3.5640 ppm/gm respectively from the $2^{nd}$ to the $8^{th}$ week of exposure. In acute and chronic copper toxicity, there was degenerative changes in renal tubules. Melanophores aggregation in the wall of the blood vessels of the spleen and depletion of some of the melanophores in the melanomachrophage were seen together with necrosis in some areas. Congested Mvs (Micro vessels) and vacuolation of hepatocytes were observed. Some areas of hemorrhage and melanophores vacuolar degeneration in the liver were seen. There was mitosis in some areas with displesia of hepatopancreatic cells and eosinophilic granular cells aggregation. Zymogen granules disappeared and there were dyplastic hepatocytes. Congestion in the blood vessels of the gill filaments, associated with massive number of granular eosinophilic cells infiltration were seen in the base of the filaments. There were sever vacuolization and hyalinization in the skeletal muscle bundles. Detection of residues of copper sulfate revealed increase of the amount of copper measured in ppm/gm comparing to the normal control starting from 0.60 ppm/g in the $2^{nd}$ day, 0.67 ppm/g in the $5^{th}$ day and 0.67 ppm/g in the $7^{th}$ day. Result obtained in chronic copper sulfate toxicity revealed gradual increase of the amount of copper which ranged from 0.18 ppm/g at the $2^{nd}$ week to 0.21 ppm/g in the $8^{th}$ week of exposure.

• 생명과학회지
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• 제19권12호
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• pp.1731-1736
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• 2009

최근의 연구에서 생쥐에 장기간 서구식 사료를 급여했을 때 내인성 SHP 단백질의 수준이 증가함을 보고하였다. 또한 HepG2 세포배양을 통한 실험에서, CDCA 처리가 내인성 SHP 단백질의 수준을 증가시킬 뿐만 아니라 외인성으로 발현된 flag-SHP의 분해율을 감소시켰다. 그리고 HepG2 세포를 ad-flag-SHP로 유전자 형질전환 시켰을 때, 담즙산에 의해 유도되어진 소장 FGF-19이 외인성으로 발현된 flag-SHP 단백질의 반감기를 증가시켰다. 그러나 cholic acid와 FGF-19에 의한 내인성 SHP 단백질의 발현수준과 분해율은 생쥐 또는 배양된 간암세포주에서 아직 명확히 이해되고 있지 않다. 이 연구는 cholic acid의 처리가 생쥐에서 내인성 SHP 단백질의 수준에 미치는 영향과, FGF-19이 HepG2 세포주에서 내인성 SHP 단백질의 분해율에 미치는 영향을 조사하였다. 정상적인 사료를 급여한 대조군 생쥐에서의 내인성 SHP 단백질 수준과 비교하여, 0.5%의 cholic acid를 첨가한 사료를 급여한 생쥐에서는 12시간과 24시간의 처리기간 동안에 내인성 SHP 단백질의 수준이 증가하였다. 배양된 인간 간암세포주인 HepG2에서 CDCA의 처리는 CDCA를 처리하지 않은 대조군 세포주와 비교하여 내인성 SHP 단백질의 분해율을 유의성 있게 변화시키지 않았다. 한편 외인성 ad-flag-SHP 단백질에 대한 이전의 연구와 일치하게, HepG2 세포에 cyclohexamide를 처리하였을 때 FGF-19는 내인성 SHP 단백질의 분해율을 현저히 감소시켰다. 이러한 결과는 담즙산과 FGF-19 모두 생쥐의 간과 HepG2 세포주에서 내인성 SHP 단백질의 수준을 증가시킴을 제시한다.

• Journal of Microbiology
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• 제37권2호
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• pp.90-96
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• 1999

The core protein of the hepatitis C virus (HCV) is a multifunctional protein. The HCV core protein was reported to regulate cellular gene expression and transform primary rat embryo fibroblast cells. However, the role of the core protein in the pathogenesis of HCV-associated liver diseases is not well understood. To investigate the functional role of the core protein in cytophathogenicity, we have constructed stable expression systems of full length or truncated HCV core protein lacking the C-terminal hyderophobic domains and established HepG2 cell clones constitutively expressing the core protein. The full length core protein was localized in the cytoplasm and the C-terminal truncated core protein was localized in the nucleus. HepG2 cells expressing nuclear, truncated core protein showed elevated cell death during cultivation compared to untransfected cells and full length core-expressing cells. In the treatment with bleomycin, both cell clones expressing full length or truncated core protein appeared to be more sensitive to blemoycin than the parental HepG2 cells. These results suggest that the core protein may play a role in HCV pathogenesis promoting apoptotic cell death of infected cells.

• Preventive Nutrition and Food Science
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• 제8권3호
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• pp.284-288
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• 2003

In this study, we investigated the effects of green tea and Pueraria radix tea on the production of Apo B$_{100}$ in Hep G$_2$ liver cells and on the expression of the low density lipoprotein (LDL) receptor. Treatment with green tea resulted in a 60.7% decrease on the Apo B$_{100}$ concentration in Hep G$_2$ cells. Pueraria radix tea decreased Apo B$_{100}$ concentration by 63.5% in Hep G$_2$ cells. Green tea and Pueraria radix tea significantly decreased Apo B$_{100}$ concentration by 64.8% and 61.8%, respectively, in the media. Treatment of the cells with green tea and Pueraria radix tea also significantly decreased the intracellular total cholesterol, but total cholesterol concentrations in the media increased by 26.4% (green tea) and 23.6% (Pueraria radix tea) above that measured in the media of control cells. The addition of green tea and Pueraria radix to the media of the Hep Gz cells increased the LDL receptor binding activities by 84.1% and 79.4%, respectively.

• Asian-Australasian Journal of Animal Sciences
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• 제19권8호
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• pp.1100-1105
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• 2006

During involution of the mammary gland after the lactation period, the gland undergoes an extensive epithelial cell death. In our previous study, overexpression of an extracellular proteinase inhibitor (Expi) gene accelerated apoptosis of mammary epithelial cells. Here we found that expression of the cathepsin D gene was induced in the Expi-overexpressed apoptotic cells. To understand the role of cathepsin D in apoptosis, we transfected cathepsin D gene into mammary epithelial HC11 cells and established the stable cell lines overexpressing the cathepsin D gene. We found that overexpression of the cathepsin D gene partially induced apoptosis of mammary epithelial cells. Expression patterns of the cathepsin D gene were examined in mouse mammary gland at various reproductive stages. Expression of the cathepsin D gene was increased during involution stages compared to lactation stages, and highest expression levels were shown at involution on day 4. We also examined expression of the cathepsin D gene in various mouse tissues. Mammary gland at involution on day 2 showed highest levels of cathepsin D mRNA of the mouse tissues that we examined. Liver tissues showed high levels of cathepsin D expression. These results demonstrate that cathepsin D may contribute to the apoptotic process of mammary epithelial cells.

• Biomolecules & Therapeutics
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• 제5권1호
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• pp.59-66
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• 1997

This study was done to determine that vitamins I and C are synergistic in protecting liver cells during hepatic ischemia and repefusion. Rats treated with vitamins I and C were subjected to 60 min of hepatic ischemia and to 1 and 5 hr of reperfusion thereafter. Serum aminotransferase level and microsomal lipid peroxidation were markedly increased by ischemia/reperfusion. These increases were significantly attenuated by vitamins E, C or its combination. Hepatic wet weight-to-dry weight ratio was increased in ischemic group, but this increase was prevented by combination of vitamin I and C. Bile flow and cholate output were markedly decreased by ischemia/reperfusion and vitamin C alone and combination of vitamin I and C restored their secretion. Cytochrome P-450 content and aminopyrine N-demethylase activity were decreased by ischemia/ reperfusion and restored by vitamin C and combination of vitamin I and C to the level of sham-operated rat. Aniline p-hydroxylase activity was increased by ischemia/reperfusion and this increase was prevented by vitamin E. Our findings suggest that ischemia/reperfusion diminishes hepatic secretory and microsomal functions by increasing lipid peroxidation and vitamins I and C synergistically ameliorates these changes.

• 한국환경농학회지
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• 제28권4호
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• pp.462-467
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• 2009

Exposure of formaldehyde (FA), one of the major compounds in pesticides and in the onset of sick house syndrome, has been implicated in the development of diverse diseases. Liver is a very important organ to body metabolism and drug detoxification. Apotosis of hepatocytes is associated with the onset of liver diseases such as hepatitis. However, the apoptotic effect of FA in hepatocytes is not clear. Therefore, this study was conducted to investigate the effect of FA on the apoptosis in HepG2 cells, a human hepatocyte cell line. As a result, FA (> $500\;{\mu}M$) decreased cell viability and increased lactate dehydrogenase activity in HepG2 cells, which was blocked by the treatment of vitamin E and N-acetylcysteine (NAC). In addition, FA decreased glutathione (GSH) contents and Bcl-2 levels, while increasing lipid peroxide formation and Bax levels. It also cleaved caspase-3 form, which was blocked by the treatment of vitamin E and NAC. It is insisted that FA induced apoptosis via oxidative stress in human hepatocytes.