• 한국식품영양과학회지
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• 제15권2호
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• pp.191-200
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• 1986

It is now generally accepted that individuals at increased risk for cardiovascular disease may be identified by certain traits or habbits. The factors such as high blood pressure, elevated blood cholestrol, age, sex and obesity are associated with increseaed frequency of disease. The blood cholesterol level lowering will decrease cardiovascular disease risk. The regression of atherosclerosis can be achieved by lowering the level of circulating cholesterol. Those things are connected with the quantity and quality of protein, fats, carbohydrates, especially soluble and non-soluble fiber, magnesium and calcium. The lipoprotein and lipid metabolism are connected with the lipid transport. The factors on lipid absorption and blood serum lipid pattern of human are exist. The factors have a variety of materials with different chemical and physical properties. The soluble fiber diet make a low blood and liver lipids. Many kind of soluble fiber results in a lowering of blood cholesterol and triglyceride levels. The cholesterol lowering effects of dietery fiber may be a results of alterations of in intestinal handling of fats, hepatic metabolism of fatty acid or triglyceride acid metabolism of lipoprotein. It is investigated that the high density lipoprotein (HDL) is inversely related to coronary artery disease. It has been postulated that HDL may be an important factor in cholesterol efflux from the tissues, therby reducing the amount of cholesterol deposited there. Alternatively, the HDL may pick up cholestyl ester and phospholipid during normal VLDL lipolysis in the plasma. The HDL levels are relatively insensitive to diet. At present time, the cause-and -diet effect of HDL's inverse relation to CHD remains unclear.

• Asian-Australasian Journal of Animal Sciences
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• 제20권9호
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• pp.1334-1341
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• 2007

This study identified hepatic differentially expressed genes (DEGs) affecting the marbling of muscle. Most dietary nutrients bypass the liver and produce plasma lipoproteins. These plasma lipoproteins transport free fatty acids to the target tissue, adipose tissue and muscle. We examined hepatic genes differentially expressed in a differential-display reverse transcription-polymerase chain reaction (ddRT-PCR) analysis comparing high- and low-marbled Hanwoo steers. Using 60 arbitrary primers, we found 13 candidate genes that were upregulated and five candidate genes that were downregulated in the livers of high-marbled Hanwoo steers compared to low-marbled individuals. A BLAST search for the 18 DEGs revealed that 14 were well characterized, while four were not annotated. We examined four DEGs: ATP synthase F0, complement component CD, insulin-like growth factor binding protein-3 (IGFBP3) and phosphatidylethanolamine binding protein (PEBP). Of these, only two genes (complement component CD and IGFBP3) were differentially expressed at p<0.05 between the livers of high- and low-marbled individuals. The mean mRNA levels of the PEBP and ATP synthase F0 genes did not differ significantly between the livers of high- and low-marbled individuals. Moreover, these DEGs showed very high inter-individual variation in expression. These informative DEGs were assigned to the bovine chromosome in a BLAST search of MS marker subsets and the bovine genome sequence. Genes related to energy metabolism (ATP synthase F0, ketohexokinase, electron-transfer flavoprotein-ubiquinone oxidoreductase and NADH hydrogenase) were assigned to BTA 1, 11, 17, and 22, respectively. Syntaxin, IGFBP3, decorin, the bax inhibitor gene and the PEBP gene were assigned to BTA 3, 4, 5, 5, and 17, respectively. In this study, the in silico physical maps provided information on the specific location of candidate genes associated with economic traits in cattle.

• 한국가금학회지
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• 제46권3호
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• pp.161-171
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• 2019

본 연구는 한국 재래닭에서 Zn 보충제 급여가 체내 항산화 지표 및 아연운반체 발현에 미치는 영향을 조사하기 위하여 기초사료(100 ppm, 대조군)에 산화아연(ZnO) 또는 Zn-methionine(ZnM)을 각각 50 ppm을 첨가하여 모두 3개군으로 설정하여 4주간 사양시험을 실시하였다. 혈중 total protein, albumin, blood urea nitrogen과 같은 질소화합물은 처리군들 간 차이가 없었으나, uric acid는 ZnM군에서 ZnO군보다 유의하게(P<0.05) 증가되었다. 혈액의 총 항산화능과 지질과산화도에서는 아연의 급여원에 따른 차이는 없었다. 소장에서 항산화 효소 활성도 및 지질과산화도를 조사한 결과, superoxide dismutase(SOD), glutathione peroxidase(GPX) 및 지질과산화도는 아연의 보충급여 및 급여원에 따른 차이는 없었으나, glutathione S-transferase (GST) 활성도는 ZnM군에서 대조군에 비해 현저히(P<0.05) 증가되었다. 간 조직에서 SOD와 GPX 활성도 및 지질과산화도는 처리군간 비슷한 수준을 보였으나, GST는 ZnM군에서 대조군에 비해 현저히(P<0.05) 증가하였다. 소장 흡수세포에서 아연 운반단백질 ZnT-1(8.62배 P=0.09) 및 ZnT-5(7.3배, P=0.06) mRNA 발현은 ZnM군에서 증가되는 경향은 보였으나, 통계적 차이는 인정되지 않았다. 간에서 아연운반체 mRNA 발현은 아연급여에 따른 통계적 차이는 없었으나, ZnM군에서 대조군에 비해 MT mRNA 발현이 4.12배 증가되는 경향(P=0.10)을 보였다. 이상의 결과로 보아 기초사료에 Zn-methionine 보충급여(50 ppm)는 재래닭의 소장 및 간 조직에서 GST 활성도를 유의하게 증가시키고, 소장에서 아연운반체 mRNA 발현을 증가시키는 경향을 보여 유기태 아연급여는 체내 산화적 스트레스 방어 긍정적인 영향을 미칠 수 있는 것으로 생각된다.

• Asian-Australasian Journal of Animal Sciences
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• 제22권6호
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• pp.871-884
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• 2009

Gene expression profiling is a useful tool for identifying critical genes and pathways in metabolism. The objective of this study was to determine the major differences in the expression of genes associated with metabolism and metabolic regulation in liver and mammary tissues of lactating cows. We used the Michigan State University bovine metabolism (BMET) microarray; previously, we have designed a bovine metabolism-focused microarray containing known genes of metabolic interest using publicly available genomic internet database resources. This is a high-density array of 70mer oligonucleotides representing 2,349 bovine genes. The expression of 922 genes was different at p<0.05, and 398 genes (17%) were differentially expressed by two-fold or more with 222 higher in liver and 176 higher in mammary tissue. Gene ontology categories with a high percentage of genes more highly expressed in liver than mammary tissues included carbohydrate metabolism (glycolysis, glucoenogenesis, propanoate metabolism, butanoate metabolism, electron carrier and donor activity), lipid metabolism (fatty acid oxidation, chylomicron/lipid transport, bile acid metabolism, cholesterol metabolism, steroid metabolism, ketone body formation), and amino acid/nitrogen metabolism (amino acid biosynthetic process, amino acid catabolic process, urea cycle, and glutathione metabolic process). Categories with more genes highly expressed in mammary than liver tissue included amino acid and sugar transporters and MAPK, Wnt, and JAK-STAT signaling pathways. Real-time PCR analysis showed consistent results with those of microarray analysis for all 12 genes tested. In conclusion, microarray analyses clearly identified differential gene expression profiles between hepatic and mammary tissues that are consistent with the differences in metabolism of these two tissues. This study enables understanding of the molecular basis of metabolic adaptation of the liver and mammary gland during lactation in bovine species.

• BMB Reports
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• 제48권9호
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• pp.513-518
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• 2015

Factors that modulate cholesterol levels have major impacts on cardiovascular disease. Niemann-Pick C1-like 1 (NPC1L1) functions as a sterol transporter mediating intestinal cholesterol absorption and counter-balancing hepatobiliary cholesterol excretion. The liver receptor homolog 1 (LRH-1) had been shown to regulate genes involved in hepatic lipid metabolism and reverse cholesterol transport. To study whether human NPC1L1 gene is regulated transcriptionally by LRH-1, we have analyzed evolutionary conserved regions (ECRs) in HepG2 cells. One ECR was found to be responsive to the LRH-1. Through deletion studies, LRH-1 response element was identified and the binding of LRH-1 was demonstrated by EMSA and ChIP assays. When SREBP2, one of several transcription factors which had been shown to regulate NPC1L1 gene, was co-expressed with LRH-1, synergistic transcriptional activation resulted. In conclusion, we have identified LRH-1 response elements in NPC1L1 gene and propose that LRH-1 and SREBP may play important roles in regulating NPC1L1 gene. [BMB Reports 2015; 48(9): 513-518]

• Journal of Pharmaceutical Investigation
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• 제22권1호
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• pp.11-21
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• 1992

The effects of colchicine on the plasma elimination and biliary excretion of various organic anions in rats were examined. Elimination of indocyanine green (ICG) or rose bengal (RB) from plasma was significantly delayed when rats were treated with colchicine (3 mg/kg body weight) 3 hr prior to the administration of the dye. On the other hand, disappearance of sulfobromophthalein (BSP) or bromophenol blue (BPB) from plasma was not influenced by colchicine. The plasma disappearance and biliary excretion of organic anions were kinetically analyzed based on a compartment model, in which the deep compartment and the unknown disposition are incorporated. The transfer rate constants of ICG or RB, $k_{23}$ (from the liver to the deep compartment) and $k_{3B}$ (from the deep compartment to the bile), were decreased by colchicine, but those of BSP or BPB were not changed. A mechanism for the decrease in the $k_{23}$ and $k_{3B}$ values for ICG and RB might be explained by a inhibition of colchicine to the intracellular cytoskeleton. The hepatocellular distribution of RB or BPB was then determined. BPB mainly distributed to the cytosolic fraction, but RB distributed to each hepatocyte organelle. Taken together. it was suggested that ICG or RB is transported through hepatocytes into bile with the aid of the cytoskeleton, whereas BSP or BPB is handled by hepatocytes in a different way.

• Parasites, Hosts and Diseases
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• 제59권3호
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• pp.189-225
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• 2021

The use of albendazole and mebendazole, i.e., benzimidazole broad-spectrum anthelmintics, in treatment of parasitic infections, as well as cancers, is briefly reviewed. These drugs are known to block the microtubule systems of parasites and mammalian cells leading to inhibition of glucose uptake and transport and finally cell death. Eventually they exhibit ovicidal, larvicidal, and vermicidal effects on parasites, and tumoricidal effects on hosts. Albendazole and mebendazole are most frequently prescribed for treatment of intestinal nematode infections (ascariasis, hookworm infections, trichuriasis, strongyloidiasis, and enterobiasis) and can also be used for intestinal tapeworm infections (taeniases and hymenolepiasis). However, these drugs also exhibit considerable therapeutic effects against tissue nematode/cestode infections (visceral, ocular, neural, and cutaneous larva migrans, anisakiasis, trichinosis, hepatic and intestinal capillariasis, angiostrongyliasis, gnathostomiasis, gongylonemiasis, thelaziasis, dracunculiasis, cerebral and subcutaneous cysticercosis, and echinococcosis). Albendazole is also used for treatment of filarial infections (lymphatic filariasis, onchocerciasis, loiasis, mansonellosis, and dirofilariasis) alone or in combination with other drugs, such as ivermectin or diethylcarbamazine. Albendazole was tried even for treatment of trematode (fascioliasis, clonorchiasis, opisthorchiasis, and intestinal fluke infections) and protozoan infections (giardiasis, vaginal trichomoniasis, cryptosporidiosis, and microsporidiosis). These drugs are generally safe with few side effects; however, when they are used for prolonged time (>14-28 days) or even only 1 time, liver toxicity and other side reactions may occur. In hookworms, Trichuris trichiura, possibly Ascaris lumbricoides, Wuchereria bancrofti, and Giardia sp., there are emerging issues of drug resistance. It is of particular note that albendazole and mebendazole have been repositioned as promising anti-cancer drugs. These drugs have been shown to be active in vitro and in vivo (animals) against liver, lung, ovary, prostate, colorectal, breast, head and neck cancers, and melanoma. Two clinical reports for albendazole and 2 case reports for mebendazole have revealed promising effects of these drugs in human patients having variable types of cancers. However, because of the toxicity of albendazole, for example, neutropenia due to myelosuppression, if high doses are used for a prolonged time, mebendazole is currently more popularly used than albendazole in anti-cancer clinical trials.

• 생명과학회지
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• 제20권7호
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• pp.1019-1026
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• 2010

과체중과 비만은 당뇨병, 고혈압, 고지혈증과 같은 신진 대사 질환의 발병과 강력하게 연관되어 있다. 비만의 원인은 여러가지가 있겠지만, 고지방식이는 비만의 원인 중 가장 중요한 요소 중 하나이다. 본 연구에서는 C57BL/6 생쥐에게 22주간의 고지방 식이를 주었으며, 이를 통해 비만과 고혈당을 유도하였다. 22주 후에 고지방식이를 한 생쥐들에서 체중과 혈장 포도당 수준이 정상 식이를 한 생쥐들에 비해 크게 증가함을 관찰하였다. 복막 내 당 부하 검사(IPGTT)에서도 고지방 식이를 한 생쥐들은 정상 식이를 한 생쥐들에 비해서 당 내성 이상 반응을 보여주었다. 이러한 결과들은 고지방식이가 C57BL/6 생쥐에서 비만 및 고혈당을 유도한다는 사실을 확인시켜 주었다. 고지방식이군 생쥐들에서는 정상식이군의 생쥐들에 비해 혈장의 중성지방과 총 콜레스테롤의 양이 증가됨이 관찰되었다. 간에서의 중성지방 및 총 콜레스테롤의 수준도 역시 증가하였다. 따라서, 간에서의 지질대사가 어떻게 변하였는지를 알기 위해, 지질대사에 관련된 단백질들의 변화를 관찰하였다. 지방 합성과 관련된 효소들 중 FAS와 GPAT가 고지방식이 군에서 의미있게 증가 되어있었으며, 지방 수송에 관련하는 단백질 중에서도 ApoB 및 MTP의 큰 증가가 고지방식이군에서 관찰되었다. 흥미롭게도, 대사 조절 인자로 알려진 AMPK의 단백질의 양과 인산화 정도는 정상식이군에 비해 고지방식이군에서 의미있게 증가되었음이 관찰되었다. 결론적으로, 본 연구에서 우리는 고지방식이가 지질 합성과 지질 수송과정을 생리학적으로 증가시키지만, 역설적으로 AMPK의 활성화를 유발한다는 것을 확인하였다.

• 한국어류학회지
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• 제18권2호
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• pp.65-77
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• 2006

우리나라 주요 담수 어종인 미꾸라지(Misgurnus mizolepis)를 실험 모델로 이용하여 실험적으로 설정한 고온 노출($32^{\circ}C$)에 특이적으로 반응하는 유전자들을 cDNA microarray 분석을 통해 탐색하였다. 미꾸라지 간조직 expressed sequence tag (EST) 데이터베이스 분석을 통해 1,124개의 unigene들을 선발하여 제작한 cDNA microarray을 이용하여 $23^{\circ}C$ 및 $32^{\circ}C$에 4주간 노출된 실험어의 간(liver)조직의 전사 발현 양상을 3반복 분석하였다. 다양한 유전자군이 $32^{\circ}C$ 고온 노출에 전사 발현의 증감 또는 감소 양상을 보였으며 $23^{\circ}C$에 비해 $32^{\circ}C$군에서 2배 이상의 발현 증가를 보인 클론들은 총 93종류로서 에너지 대사, 단백질 대사, 면역/항산화 기능, 세포골격 및 구조, 물질수송 및 세포 신호전달등에 관여하는 단백질들을 암호화하는 유전자들이었고 최대 15배 이상의 전사발현이 관찰되었다. 반면 고온 노출군에서 유의적인 발현 감소(50% 이하)를 보인 유전자들(n=85) 역시 탐색되어 상기 단백질 분류군외에 vitellogenin 전구체들 및 리보좀 단백질류에서 특이적인 전사활성의 저하가 관찰되었고, vitellogenin 유전자에서 가장 많은 mRNA 수준의 감소가 관찰되었다.

• Archives of Pharmacal Research
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• 제28권3호
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• pp.249-268
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• 2005

Drug metabolizing enzymes (DMEs) play central roles in the metabolism, elimination and detoxification of xenobiotics and drugs introduced into the human body. Most of the tissues and organs in our body are well equipped with diverse and various DMEs including phase I, phase II metabolizing enzymes and phase III transporters, which are present in abundance either at the basal unstimulated level, and/or are inducible at elevated level after exposure to xenobiotics. Recently, many important advances have been made in the mechanisms that regulate the expression of these drug metabolism genes. Various nuclear receptors including the aryl hydrocarbon receptor (AhR), orphan nuclear receptors, and nuclear factor-erythoroid 2 p45-related factor 2 (Nrf2) have been shown to be the key mediators of drug-induced changes in phase I, phase II metabolizing enzymes as well as phase III transporters involved in efflux mechanisms. For instance, the expression of CYP1 genes can be induced by AhR, which dimerizes with the AhR nuclear translocator (Arnt) , in response to many polycyclic aromatic hydrocarbon (PAHs). Similarly, the steroid family of orphan nuclear receptors, the constitutive androstane receptor (CAR) and pregnane X receptor (PXR), both heterodimerize with the ret-inoid X receptor (RXR), are shown to transcriptionally activate the promoters of CYP2B and CYP3A gene expression by xenobiotics such as phenobarbital-like compounds (CAR) and dexamethasone and rifampin-type of agents (PXR). The peroxisome proliferator activated receptor (PPAR), which is one of the first characterized members of the nuclear hormone receptor, also dimerizes with RXR and has been shown to be activated by lipid lowering agent fib rate-type of compounds leading to transcriptional activation of the promoters on CYP4A gene. CYP7A was recognized as the first target gene of the liver X receptor (LXR), in which the elimination of cholesterol depends on CYP7A. Farnesoid X receptor (FXR) was identified as a bile acid receptor, and its activation results in the inhibition of hepatic acid biosynthesis and increased transport of bile acids from intestinal lumen to the liver, and CYP7A is one of its target genes. The transcriptional activation by these receptors upon binding to the promoters located at the 5-flanking region of these GYP genes generally leads to the induction of their mRNA gene expression. The physiological and the pharmacological implications of common partner of RXR for CAR, PXR, PPAR, LXR and FXR receptors largely remain unknown and are under intense investigations. For the phase II DMEs, phase II gene inducers such as the phenolic compounds butylated hydroxyanisol (BHA), tert-butylhydroquinone (tBHQ), green tea polyphenol (GTP), (-)-epigallocatechin-3-gallate (EGCG) and the isothiocyanates (PEITC, sul­foraphane) generally appear to be electrophiles. They generally possess electrophilic-medi­ated stress response, resulting in the activation of bZIP transcription factors Nrf2 which dimerizes with Mafs and binds to the antioxidant/electrophile response element (ARE/EpRE) promoter, which is located in many phase II DMEs as well as many cellular defensive enzymes such as heme oxygenase-1 (HO-1), with the subsequent induction of the expression of these genes. Phase III transporters, for example, P-glycoprotein (P-gp), multidrug resistance-associated proteins (MRPs), and organic anion transporting polypeptide 2 (OATP2) are expressed in many tissues such as the liver, intestine, kidney, and brain, and play crucial roles in drug absorption, distribution, and excretion. The orphan nuclear receptors PXR and GAR have been shown to be involved in the regulation of these transporters. Along with phase I and phase II enzyme induction, pretreatment with several kinds of inducers has been shown to alter the expression of phase III transporters, and alter the excretion of xenobiotics, which implies that phase III transporters may also be similarly regulated in a coordinated fashion, and provides an important mean to protect the body from xenobiotics insults. It appears that in general, exposure to phase I, phase II and phase III gene inducers may trigger cellular 'stress' response leading to the increase in their gene expression, which ultimately enhance the elimination and clearance of these xenobiotics and/or other 'cellular stresses' including harmful reactive intermediates such as reactive oxygen species (ROS), so that the body will remove the 'stress' expeditiously. Consequently, this homeostatic response of the body plays a central role in the protection of the body against 'environmental' insults such as those elicited by exposure to xenobiotics.