• BMB Reports
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• v.34 no.4
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• pp.385-389
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• 2001

Insulin-like growth factor binding protein-1 (IGFBP-1) appears to be an important modular of the insulin growth factor (IGF) bioactivity in metabolic disease and chronic hypoxia. Treatment of desferrioxamine (Dfo), cobalt, or nickel in HepG2 cells stimulated the expression of IGFBP1 mRNA as hypoxia. However, the presence of ferric ammonium citrate (FAC) in the 1% $O_2$ decreased the upregulation of the IGFBP-1 mRNA expression. In addition, actinomycin D and cycloheximide abolished the increase in the expression of IGFBP-1 mRNA that was induced by Dfo and transition metals (cobalt and nickel). To obtain further information about the putative oxygen sensor, we postulate that putative heme proteins, responsible for the oxygen-sensing process in HepG2 cells, should be sensitive to hypoada. The mechanism of these upregulations of the IGFBP-1 mRNA expression by Dfo and transition metals was investigated by treatment with 2 mM of 4,6-dioxoheptanoic acid (DHA), an inhibitor of heme biosynthesis. The results showed that 1% $O_2$-, Dfo-, cobalt-, or nickel induced IGFBP-1 mRNA expressions in HepG2 cells were all markedly inhibited when the heme synthesis was blocked by DHA. We suggest that the IGFBP-1 mRNA expression in the HepG2 cell is regulated by 1% $O_2$, Dfo, cobalt, or nickel, implicating the involvement of the putative heme-containing oxygensensing molecule.

• Nutrition Research and Practice
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• v.1 no.3
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• pp.231-236
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• 2007

Underreporting patterns by the level of obesity have not been fully assessed yet. The purpose of this study was to examine the differential underreporting patterns on cardiovascular risk factor, macronutrient, and food group intakes by the level of Body Mass Index (BMI). We analyzed cross-sectional baseline nutritional survey data from the population-based longitudinal study, the Healthy Women Study (HWS) cohort. Study subjects included 538 healthy premenopausal women participating in the HWS. Nutrient and food group intakes were assessed by the one-day 24-hour dietary recall and a semi-quantitative food frequency questionnaire, respectively. The ratio of reported energy intake (EI) to estimated basal metabolic rate (BMR) was used as a measure of relative energy reporting status and categorized into tertiles. Overweight group ($BMI{\geq}25kg/m^2$) had a higher ratio of EI to BMR (EI/BMR) than normal weight group ($BMI<25kg/m^2$). Normal weight and overweight groups showed similar patterns in cardiovascular risk factors, nutrient intake, and food group intake by the EI/BMR. Fat and saturated fat intakes as a nutrient density were positively associated with the EI/BMR. Proportion of women who reported higher consumption (${\geq}4\;times/wk$) of sugar/candy, cream and red meat groups was greater in higher tertiles of the EI/BMR in both BMI groups. Our findings suggest similar patterns of underreporting of cardiovascular risk factors, and macronutrient and food group intakes in both normal and overweight women.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.4
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• pp.457-465
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• 2018

The expression of BCL-2 interacting cell death suppressor (BIS), an anti-stress or anti-apoptotic protein, has been shown to be regulated at the transcriptional level by heat shock factor 1 (HSF1) upon various stresses. Recently, HSF1 was also shown to bind to BIS, but the significance of these protein-protein interactions on HSF1 activity has not been fully defined. In the present study, we observed that complete depletion of BIS using a CRISPR/Cas9 system in A549 non-small cell lung cancer did not affect the induction of heat shock protein (HSP) 70 and HSP27 mRNAs under various stress conditions such as heat shock, proteotoxic stress, and oxidative stress. The lack of a functional association of BIS with HSF1 activity was also demonstrated by transient downregulation of BIS by siRNA in A549 and U87 glioblastoma cells. Endogenous BIS mRNA levels were significantly suppressed in BIS knockout (KO) A549 cells compared to BIS wild type (WT) A549 cells at the constitutive and inducible levels. The promoter activities of BIS and HSP70 as well as the degradation rate of BIS mRNA were not influenced by depletion of BIS. In addition, the expression levels of the mutant BIS construct, in which 14 bp were deleted as in BIS-KO A549 cells, were not different from those of the WT BIS construct, indicating that mRNA stability was not the mechanism for autoregulation of BIS. Our results suggested that BIS was not required for HSF1 activity, but was required for its own expression, which involved an HSF1-independent pathway.

• Molecules and Cells
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• v.23 no.2
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• pp.246-251
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• 2007

Osteoporosis is a common metabolic bone disease characterized by low bone mineral density (BMD) with an increased risk of fracture. Low bone mass results from an imbalance between bone formation by osteoblasts and bone resorption by osteoclasts. Microphthalmia-associated transcription factor (MITF) plays a critical role in osteoclast development and thus is an important candidate gene affecting bone turnover and BMD. In order to investigate the genetic effects of MITF variations on osteoporosis, we directly sequenced the MITF gene in 24 Koreans, and identified fifteen sequence variants. Two polymorphisms (+227719C > T and +228953A > G) were selected based on their allele frequencies, and then genotyped in a larger number of postmenopausal women (n = 560). Areal BMD ($g/cm^2$) of the anterior-posterior lumbar spine and the non-dominant proximal femur was measured by dual-energy X-ray absorptiometry. We found that the MITF + 227719C > T polymorphism was significantly associated with low BMD of the trochanter (p = 0.005-0.006) and total femur (p = 0.02-0.03) (codominant and dominant models), while there was no association with BMD of the lumbar spine. The MITF+228953A > G polymorphism was also associated with low BMD of the femoral shaft (p = 0.05) in the recessive model. Haplotype analysis showed that haplotype 3 of the MITF gene (MITF-ht3) was associated with low BMD of the trochanter (p = 0.03-0.05) and total femur (p = 0.05) (dominant and codominant models). Our results suggest that MITF variants may play a role in the decreased BMD of the proximal femur in postmenopausal women.

• The Korea Journal of Herbology
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• v.35 no.5
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• pp.23-31
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• 2020

Objectives : This study was conducted to evaluate the anti-hyperlipidemia effect of Scutellariae Radix, Aucklandiae Radix and Bupleuri Radix(SAB). Methods : FL83B cells were mouse liver hepatocytes, and we used this cell line. FL83B cells were treated with 0.5 mM oleic acid(OA) for 24 h, SAB extract was treated. After OA treatment, intracellular triglyceride (TG) and free fatty acid contents were measured with AdiopoRed™ assay and Free Fatty Acid Quantitation assay kit, respectively. Further, we evaluated several lipogenesis and metabolic markers such as sterol regulatory element-binding transcription factor-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), 3-hydroxy3-methyl-glutaryl CoA reductase (HMGCR), hormone-sensitive lipase (HSL), carnitine palmitoyltransferase (CPT-1), peroxisome proliferator activated receptor alpha (PPARα), and cluster of differentiation (CD36) using RT-PCR and Western-blot analysis. Results : OA markedly increased intracellular TG and free fatty acid, which plays a key role in reducing hepatic lipid accumulation, in FL83B cells. These increases were alleviated by SAB extract. The mRNA and protein expression of Fatty acid(FA) oxidation factors (CPT-1, PPARα), lipolysis factor(HSL), FA transporter(CD36), cholesterol synthesis factors (HMGCoA) and Lipodenesis (SREBP-1c, FAS, and ACC-1) were significantly increased by treatment of SAB extract in the OA-induced fatty liver cell model. Conclusions : In summary, the treat of SAB extract showed a significant reduction of the influx of fatty acids into hepatocytes, promoted the oxidation of fatty acids, and regulated fat synthesis-related factors, thereby regulating the accumulation of TG and free fatty acids.

• BMB Reports
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• v.48 no.10
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• pp.583-588
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• 2015

Microtubule actin crosslinking factor 1 (MACF1), a widely expressed cytoskeletal linker, plays important roles in various cells by regulating cytoskeleton dynamics. However, its role in osteoblastic cells is not well understood. Based on our previous findings that the association of MACF1 with F-actin and microtubules in osteoblast-like cells was altered under magnetic force conditions, here, by adopting a stable MACF1-knockdown MC3T3-E1 osteoblastic cell line, we found that MACF1 knockdown induced large cells with a binuclear/multinuclear structure. Further, immunofluorescence staining showed disorganization of F-actin and microtubules in MACF1-knockdown cells. Cell counting revealed significant decrease of cell proliferation and cell cycle analysis showed an S phase cell cycle arrest in MACF1-knockdown cells. Moreover and interestingly, MACF1 knockdown showed a potential effect on cellular MTT reduction activity and mitochondrial content, suggesting an impact on cellular metabolic activity. These results together indicate an important role of MACF1 in regulating osteoblastic cell morphology and function.

• Journal of the East Asian Society of Dietary Life
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• v.22 no.2
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• pp.147-162
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• 2012

Abdominal obesity is an important factor of metabolic syndrome and is known as an independent risk factor of cardiovascular disease. The purpose of this study was to examine the fatty acid intake pattern as well as the association between fatty acid intake and abdominal obesity and hyperglycemia in Korean adults. This study was based on data from the Korea National Health and Nutrition Examination Surveys (KNHANES) I, II, III, and IV. After excluding subjects who had missing data for dietary intakes, anthropometric measurments, and laboratory tests, a total of 12,320 subjects aged 20~64y (5,266 men and 7,054 women) were included in the study. Trends in individual consumption of dietary fatty acids by year were analyzed by One-way ANOVA test, and the association between fatty acid intake and abdominal obesity and hyperglycemia was analyzed by logistic regression analysis after adjusting for age, energy intake, marital status, job, education level, alcohol intake, and smoking status. In men, intakes of TFA, SFA, MUFA, FUFA, and n-6 PUFA significantly increased with year. On the other hand, intakes of TFA, SFA and FUFA significantly increased with year in women. Logistic regression analysis showed that the risk of abdominal obesity was significantly associated with intakes of PUFA, LNA and n-3 PUFA in women. However, there was no association with any fatty acid intakes in men. The risk of hyperglycemia was significantly and positively associated with intakes of TFA, SFA, PUFA, and LNA in men, but, there was no significant association with any fatty acid intakes in women. These results show that abdominal obesity and hyperglycemia are significantly associated with individual intake of fatty acids, suggesting that fatty acid type may be associated with risk of abdominal obesity and hyperglycemia. Futher, the macronutrients of measl must be properly balanced.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.6
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• pp.493-499
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• 2019

Macrophage-associated inflammation is crucial for the pathogenesis of diverse diseases including metabolic disorders. Rhodanthpyrone (Rho) is an active component of Gentiana rhodantha, which has been used in traditional Chinese medicine to treat inflammation. Although synthesis procedures of RhoA and RhoB were reported, the biological effects of the specific compounds have never been explored. In this study, the anti-inflammatory activity and mechanisms of action of RhoA and RhoB were studied in lipopolysaccharide (LPS)-stimulated macrophages. Pretreatment with RhoA and RhoB decreased inducible nitric oxide synthase and cyclooxygenase-2 expressions in RAW 264.7 cells and in thioglycollate-elicited mouse peritoneal macrophages. In addition, it downregulated transcript levels of several inflammatory genes in LPS-stimulated RAW 264.7 cells, including inflammatory cytokines/chemokines (Tnfa, Il6, and Ccl2) and inflammatory mediators (Nos2 and Ptgs2). Macrophage chemotaxis was also inhibited by treatment with the compounds. Mechanistic studies revealed that RhoA and RhoB suppressed the nuclear factor $(NF)-{\kappa}B$ pathway, but not the canonical mitogen activated protein kinase pathway, in LPS-stimulated condition. Moreover, the inhibitory effect of RhoA and RhoB on inflammatory gene expressions was attenuated by treatment with an $NF-{\kappa}B$ inhibitor. Our findings suggest that RhoA and RhoB play an anti-inflammatory role at least in part by suppressing the $NF-{\kappa}B$ pathway during macrophage-mediated inflammation.

• Herbal Formula Science
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• v.29 no.4
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• pp.167-179
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• 2021

Objectives : Oxidative stress is a important cause of liver disease, and regulation of oxidative stress is essential to maintain the normal metabolic function of the liver. Until a recent date, there has been no studies on the hepatoprotective effect of Ikwiseungyang-tang (IWSYT). Therefore, this study aims to demonstrate the hepatoprotective effect of IWSYT and its related molecular mechanisms on arachidonic acid (AA) + iron induced oxidative stress model in HepG2 cells. Methods : To determine the cytoprotective effect of IWSYT against AA + iron-induced oxidative stress, cell viability, apoptosis-related proteins, intracellular reactive oxygen species (ROS), GSH, and mitochondrial membrane potential (MMP) were measured. Nuclear factor erythroid 2-related factor 2 (Nrf2) activation was analyzed by immunoblot analysis. In addition, Nrf2 transcription activation through ARE binding was measured by reporter gene assays, and the expression of the Nrf2 target antioxidant genes were confirmed by immunoblot analysis. Results : IWSYT increased cell viability from cell death induced by AA + Iron, and inhibited apoptosis by regulating apoptosis-related proteins. Furthermore, IWSYT protected cells by inhibiting intracellular ROS production, GSH depletion, and MMP degradation. Nrf2 activation was increased by IWSYT, and Nrf2 target genes were activated by IWSYT too. Conclusions : These results suggest that IWSYT can protect hepatocytes from oxidative stress through Nrf2 activation and can be potentially applied in the prevention and treatment of liver damage.

• Genes and Genomics
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• v.40 no.11
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• pp.1199-1211
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• 2018

Soil acidification is one of major problems limiting crop growth and especially becoming increasingly serious in China owing to excessive use of nitrogen fertilizer. Only the STOP1 of Arabidopsis was identified clearly sensitive to proton rhizotoxicity and the molecular mechanism for proton toxicity tolerance of plants is still poorly understood. The main objective of this study was to investigate the transcriptomic change in plants under the low pH stress. The low pH as a single factor was employed to induce the response of the wheat seedling roots. Wheat cDNA microarray was used to identify differentially expressed genes (DEGs). A total of 1057 DEGs were identified, of which 761 genes were up-regulated and 296 were down-regulated. The greater percentage of up-regulated genes involved in developmental processes, immune system processes, multi-organism processes, positive regulation of biological processes and metabolic processes of the biological processes. The more proportion of down-regulation genes belong to the molecular function category including transporter activity, antioxidant activity and molecular transducer activity and to the extracellular region of the cellular components category. Moreover, most genes among 41 genes involved in ion binding, 17 WAKY transcription factor genes and 17 genes related to transport activity were up-regulated. KEGG analysis showed that the jasmonate signal transduction and flavonoid biosynthesis might play important roles in response to the low pH stress in wheat seedling roots. Based on the data, it is can be deduced that WRKY transcription factors might play a critical role in the transcriptional regulation, and the alkalifying of the rhizosphere might be the earliest response process to low pH stress in wheat seedling roots. These results provide a basis to reveal the molecular mechanism of proton toxicity tolerance in plants.