• Molecular & Cellular Toxicology
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• v.4 no.4
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• pp.338-347
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• 2008

Yeast RAD2, a yeast homolog of human XPG gene, is an essential element of nucleotide excision repair (NER), and its deletion confers UV sensitivity and NER deficiency. 6-Azauracil (6AU) sensitivity of certain rad2 mutants revealed that RAD2 has transcription elongation function. However, the fundamental mechanism by which the rad2 mutations confer 6AU sensitivity was not clearly elucidated yet. Using an insertional mutagenesis, PUF4 gene encoding a yeast pumilio protein was identified as a deletion suppressor of rad2${\Delta}$ 6AU sensitivity. Microarray analysis followed by confirmatory RT-qPCR disclosed that RAD2 and PUF4 regulated expression of HPT1 and URA3. Overexpression of HPT1 and URA3 rescued the 6AU sensitivity of rad2${\Delta}$ and puf4${\Delta}$ mutants. These results indicate that 6AU sensitivity of rad2 mutants is in part ascribed to impaired expression regulation of genes in the nucleotide metabolism. Based on the results, the possible connection between impaired transcription elongation function of RAD2/XPG and Cockayne syndrome via PUF4 is discussed.

• Korean Journal of Agricultural Science
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• v.40 no.3
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• pp.215-220
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• 2013

Fatty acids (FAs) were considered in activating nuclear hormone receptors that play significant roles in the cellular lipid metabolism by the regulation of several genes. Previously, fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD) genes have been known to regulating the FA metabolism. In this study, associations of FASN and SCD genes with fatty acid (FA) composition in broilers were investigated. Tissue samples from 95 Cobb 500 broilers were used for DNA extraction. The g.1222 A>G SNP located in intron 42 of FASN gene and 2 SNPs in SCD gene, one in exon 2 (g.3728A>G) and the other in exon 4 (g.12903G>A), were subjected for genotyping using PCR-RFLP method. One of the SNPs in SCD gene, SNP g.3728A>G had significant association with myristoleic acid (C14:1; P<0.05), palmitic acid (C16:0; P<0.05), palmitoleic acid (C16:1; P<0.05) and saturated FA (SFA; P<0.05). However, the SNP g.1222A>G in FASN gene had only suggestive association with arachidic acid (C20:0; P=0.08). The findings in this study suggest that the SNP in exon 2 of SCD gene can be used as a molecular marker for selecting birds having desirable FA composition in broilers.

• Toxicological Research
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• v.30 no.4
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• pp.267-276
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• 2014

Exposures to lead (Pb) are associated with neurological problems including psychiatric disorders and impaired learning and memory. Pb can be absorbed by iron transporters, which are up-regulated in hereditary hemochromatosis, an iron overload disorder in which increased iron deposition in various parenchymal organs promote metal-induced oxidative damage. While dysfunction in HFE (High Fe) gene is the major cause of hemochromatosis, the transport and toxicity of Pb in Hfe-related hemochromatosis are largely unknown. To elucidate the relationship between HFE gene dysfunction and Pb absorption, H67D knock-in Hfe-mutant and wild-type mice were given drinking water containing Pb 1.6 mg/ml ad libitum for 6 weeks and examined for behavioral phenotypes using the nestlet-shredding and marble-burying tests. Latency to nestlet-shredding in Pb-treated wild-type mice was prolonged compared with non-exposed wild-types (p < 0.001), whereas Pb exposure did not alter shredding latency in Hfe-mutant mice. In the marble-burying test, Hfe-mutant mice showed an increased number of marbles buried compared with wild-type mice (p = 0.002), indicating more repetitive behavior upon Hfe mutation. Importantly, Pb-exposed wild-type mice buried more marbles than non-exposed wild-types, whereas the number of marbles buried by Hfe-mutant mice did not change whether or not exposed to Pb. These results suggest that Hfe mutation could normalize Pb-induced behavioral alteration. To explore the mechanism of repetitive behavior caused by Pb, western blot analysis was conducted for proteins involved in brain dopamine metabolism. The levels of tyrosine hydroxylase and dopamine transporter increased upon Pb exposure in both genotypes, whereas Hfe-mutant mice displayed down-regulation of the dopamine transporter and dopamine D1 receptor with D2 receptor elevated. Taken together, our data support the idea that both Pb exposure and Hfe mutation increase repetitive behavior in mice and further suggest that these behavioral changes could be associated with altered dopaminergic neurotransmission, providing a therapeutic basis for psychiatric disorders caused by Pb toxicity.

• Preventive Nutrition and Food Science
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• v.2 no.2
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• pp.121-128
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• 1997

this study was conducted to examine the atherogenic effect of high cholesterol diet (experimental diet) that influences changes of lipoprotein cholesterol metabolism and arterial wall. Seven NewZealand white rabbits were fed control diet, an the other 7 rabbits 2% cholesterol diet for 10 weeks. Results obtained from this study are as follows: 1) High cholesterol diet resulted in a gradual increase of plasma total cholesterol level, reaching upto 1422 mg/dl at the seventh week. 2) CETP (cholesteryl ester transfer protein) activity was significantly higher in high cholesterol group (64.9% at the 7th week) than control group (49.3% at the 7th week) during most of the experimental period except the 6th week. 3) The cholesterol supplementation induced fatty liver and a decrease of hepatic HMG-CoA reductase activities (2.1 moles vs. 0.3nmoles) compared to control group. 4) Bands of apo B-100 and apo E in plasma lipoprotein were thicker in high cholesterol-fed animals tan control animals as visualized by SDS-PAGE. 5) Oxidizability of plasma lipoproteins measured in vitro was greater in high cholesterol group tan control group, but vitamin E level higher in control group. 6) he effect of cholesterol feeding for 10 weeks also led to early fatty streaks in aortic intima. High cholesterol feeding was atherogenic to rabbits, an this seems to be mediated through elevated CETP activities that regulate plasma HDL cholesterol level and decrease an efficiency of reverse cholesterol transport in lipoprotein cholesterol metabolism. The enhanced oxidizability of plasma lipoproteins and lowered vitamin E level may also contribute to the formation of faaty streaks in aorta of cholesterol-fed rabbits.

• Experimental and Molecular Medicine
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• v.50 no.12
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• pp.5.1-5.15
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• 2018

Targeting hair follicle regeneration has been investigated for the treatment of hair loss, and fundamental studies investigating stem cells and their niche have been described. However, knowledge of stem cell metabolism and the specific regulation of bioenergetics during the hair regeneration process is currently insufficient. Here, we report the hair regrowth-promoting effect of a newly synthesized novel small molecule, IM176OUT05 (IM), which activates stem cell metabolism. IM facilitated stemness induction and maintenance during an induced pluripotent stem cell generation process. IM treatment mildly inhibited mitochondrial oxidative phosphorylation and concurrently increased glycolysis, which accelerated stemness induction during the early phase of reprogramming. More importantly, the topical application of IM accelerated hair follicle regeneration by stimulating the progression of the hair follicle cycle to the anagen phase and increased the hair follicle number in mice. Furthermore, the stem cell population with a glycolytic metabotype appeared slightly earlier in the IM-treated mice. Stem cell and niche signaling involved in the hair regeneration process was also activated by the IM treatment during the early phase of hair follicle regeneration. Overall, these results show that the novel small molecule IM promotes tissue regeneration, specifically in hair regrowth, by restructuring the metabolic configuration of stem cells.

• Journal of Nutrition and Health
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• v.52 no.4
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• pp.323-331
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• 2019

Purpose: Glucocorticoids (GCs) are implicated in secondary osteoporosis, and the resulting fractures cause significant morbidity. Polyunsaturated fatty acids (PUFAs) play a vital role in bone metabolism. However, few trials have studied the impact of omega-3 PUFA-containing oils against GC-induced osteoporosis. Therefore, the present study was undertaken to determine whether supplementation with omega-3 PUFA-containing dietary oils such as fish oil, flaxseed oil or soybean oil can impede the development of GC-induced osteoporosis. Methods: The fatty acids (FAs) content of oils was determined using gas chromatography. Male rats were subdivided into 5 groups (8 rats each): normal control (balanced diet), prednisolone control (10 mg/kg prednisolone daily), soybean oil (prednisolone 10 mg/kg + soybean oil 7% w/w), flaxseed oil (prednisolone 10 mg/kg + flaxseed oil 7% w/w), and fish oil (from cod liver; prednisolone 10 mg/kg + fish oil 7% w/w). Results: The study data exhibited a significant depletion in bone mineral density (BMD) and femur mass in the prednisolone control compared to the normal control, accompanied with a marked decrease in the levels of plasma calcium and 1,25-$(OH)_2$-vitamin $D_3$, and elevated levels of C-terminal telopeptide (CTX), tumor necrosis factor-alpha (TNF-${\alpha}$) and malondialdehyde (MDA). Supplementation with fish oil, soybean oil or flaxseed oil helped to improve plasma calcium levels, and suppress oxidative stress and inflammatory markers. Additionally, bone resorption was suppressed as reflected by the decreased CTX levels. However, fish oil was more effective than the other two oils with a significant improvement in BMD and normal histological results compared to the normal control. Conclusion: This study demonstrated that supplementation with dietary oils containing omega-3 PUFAs such as fish oil, soybean oil or flaxseed oil can play a role in the prevention of bone loss and in the regulation of bone metabolism, especially fish oil which demonstrated a greater level of protection against GC-induced osteoporosis.

• The Journal of Pediatrics of Korean Medicine
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• v.33 no.2
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• pp.12-21
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• 2019

Objectives Coptidis Rhizoma and Glycyrrhiza Uralensis are herbs that treat obesity and dampness-phlegm. The aim of this study is to investigate the efficacy of Coptidis Rhizoma and Glycyrrhiza Uralensis on lipid deposition with nonalcoholic fatty liver disease (NAFLD). Methods Male 6-week-old C57BL/6 male mice were divided into three groups: control group (Ctrl), high fat diet group (HFF), and high fat diet with Coptidis Rhizoma and Glycyrrhiza Uralensis extract administration group (CGT). Each 10 mice were allocated to each group (total of 30 mice). All mice were allowed to eat fat rich diet freely throughout the experiment. To examine the effect of Coptidis Rhizoma and Glycyrrhiza Uralensis, we observed weight changes, total cholesterol and glucose levels, lipid blot distributions, PGC-1, p-$I{\kappa}B$, and p-JNK. Results Body weights for all mice were measured and analyzed the difference between the groups. Weight gain was significantly lower in CGT group than the HFF group. Total cholesterol and glucose levels were significantly lower in CGT group. The distribution of lipid blots and positive reaction of PGC-1 were significantly lower in CGT group. The positive reaction of p-$I{\kappa}B$ in hepatic tissues was significantly lower in CGT group. The positive reaction of p-JNK in hepatic tissues was significantly lower in CGT group. Conclusions Coptidis Rhizoma and Glycyrrhiza Uralensis have the effect of improving non - alcoholic fatty liver induced insulin resistance through regulation of lipid metabolism.

• Food Engineering Progress
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• v.22 no.4
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• pp.353-357
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• 2018

Previous studies have suggested that rice bran oil (RBO), an edible oil from the byproducts of rice milling, has anti-inflammatory effects in inflammation inducing macrophages, known as M1 subsets. Yet the effects of RBO on the counterpart M2 subsets, the "healing" macrophages, were poorly investigated to date. In this regard, recent studies on the molecular/cellular anti-inflammatory mechanisms of dietary components have demonstrated that mitochondrial respiration contributes to macrophage functioning. Therefore, the current study examined whether RBO regulates cytokine secretion by modulating mitochondrial metabolism in wound healing M2 subsets. Palm oil (PO), enriched with medium-chain fatty acids, served as a positive control. C57BL/6 mice were fed a diet containing either corn oil (CO), PO or RBO for 4 weeks, followed by purification of bone marrow-derived macrophages (BMDM) from their tibias and femurs. Cells were further polarized to M2-BMDM, and the expression of M2 marker (CD206) on cellular surfaces were not affected by dietary intervention. In addition, the secretion of anti-inflammatory cytokine (IL-10) in the culture supernatant was not affected by dietary lipids. Oxygen consumption rate, the indicator of mitochondrial respiration in M2-BMDM was not regulated by RBO intervention and PO treatment. Taken together, this study imply that RBO did not intervene both the regulation of inflammatory responses and mitochondrial respiration in M2 macrophages.

• Exercise Science
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• v.26 no.2
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• pp.103-114
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• 2017

INTRODUCTION: Regulation of skeletal muscle protein mass is implicated not only in exercise performance but in metabolic health. Exercise in combination with nutrition, particularly dietary protein/amino acid intake, are the pragmatic approach that effectively induces muscle anabolic response (i.e., muscle hypertrophy) through regulating protein synthesis and breakdown. PURPOSE: The purpose of this review was to summarize available data on the effect of exercise intervention and amino acids intake on muscle protein synthesis and breakdown and provide an insight into development of an effective exercise intervention and amino acids supplements, applicable to training practice. METHODS: In this review, we have reviewed currently available data mainly from stable isotope tracer studies with respect to the effect of exercise intervention and protein or amino acid supplement on muscle protein anabolic response. CONCLUSIONS: Taken together, exercise alone may not be effective in achieving a positive net muscle protein balance due to the fact that protein breakdown still exceeds protein synthesis until nutrition intake such as protein/amino acids. It appears that muscle anabolic response increases in proportional to the amount of protein intake up to 20 - 35 g depending on quality of protein, age, differences on exercise intensity, duration, and frequency, and individual's training status

• Animal Bioscience
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• v.35 no.1
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• pp.22-28
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• 2022

Objective: Endoplasmic reticulum (ER) stress engages the unfolded protein response (UPR) that serves as an important mechanism for modulating hepatic fatty acid oxidation and lipogenesis. Chronic fasting in mice induced the UPR activation to regulate lipid metabolism. However, there is no direct evidence of whether negative energy balance (NEB) induces ER stress in the liver of cows. This study aimed to elucidate the relationship between the NEB attributed to feed deprivation and ER stress in bovine hepatocytes. Methods: Blood samples and liver biopsy tissues were collected from 6 non-lactating cows before and after their starvation for 48 h. The blood non-esterified fatty acids (NEFA), β-hydroxybutyric acid (BHBA) and glucose level were analyzed. Real-time quantitative polymerase chain reaction and Western blotting were used to explore the regulation of genes associated with UPR and lipid metabolism. Results: The starvation increased the plasma BHBA and NEFA levels and decreased the glucose level. Additionally, the starvation caused significant increases in the mRNA expression level of spliced X-box binding protein 1 (XBP1s) and the protein level of phosphorylated inositol-requiring kinase 1 alpha (p-IRE1α; an upstream protein of XBP1) in the liver. The mRNA expression levels of peroxisome proliferator-activated receptor alpha and its target fatty acid oxidation- and ketogenesis-related genes were significantly upregulated by the starvation-mediated NEB. Furthermore, we found that the mRNA expression levels of lipogenic genes were not significantly changed after starvation. Conclusion: These findings suggest that in the initial stage of NEB in dairy cows, the liver coordinates an adaptive response by activating the IRE1 arm of the UPR to enhance ketogenesis, thereby avoiding a fatty liver status.