• Title/Summary/Keyword: PGC-$1{\alpha}$

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The Effect of Exercise Training (EXE) on Myocardium Glucose Metabolic Phenotypic Proteins and HSP-60 Protein Expression after Ischemia/Reperfusion Injury in STZ-induced Rats (지구성 운동이 STZ-당뇨 유발 쥐의 허혈/재 관류 손상 후 심근의 당대사 관련 표현형 단백질과 HSP-60 단백질 발현에 미치는 영향)

  • Bae, Hee-Suk;Um, Hyun-Seob;Kang, Eun-Bum;Yang, Chum-Yeol;Lee, Yong-Ro;Lee, Chang-Guk;Cheon, U-Ho;Jeon, Hye-Ja;Cho, In-Ho;Cho, Joon-Yong
    • Journal of Life Science
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    • v.19 no.5
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    • pp.644-651
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    • 2009
  • The objective of this study was to identify EXE (1 hr a day at 21 m/min for 5 day/wk, at 0 % grade for 6 wk) on myocardium glucose metabolic phenotypic proteins (AMPK-PGC-1${\alpha}$-GLUT-4) and HSP-60 protein expression after ischemia/reperfusion injury (IRI) in STZ-induced rats. EXE was performed using STZ-induced diabetic rats on a rodent treadmill (28 m/min, 1 hr/day, 5 day/wk for 6 wk). The results of this study suggest that i) serum insulin level was not changed among groups (p>l0.05). ii) the LVDP level increased significantly in the STZ-EXE-IRI group compared to the STZ-IRI group at 60 min (p<0.01), 70 min (p<0.05) and 80 min (p<0.05) after reperfusion, respectively, and iii) AMPK phosphorylation (p<0.01), PGC-1${\alpha}$ protein (p<0.001), GLUT-4 protein (p<0.001) and HSP-60 protein expressions (p<0.05) increased significantly in the STZ-EXE-IRI group compared to the STZ-IRI group. In conclusion, the findings of the present study reveal that EXE may provide therapeutic value to insulin dependent diabetic patients with peripheral insulin resistance and myocardium injury by improving glucose metabolic proteins (AMPK-PGC-1${\alpha}$-GLUT-4) and heat shock protein-60 (HSP-60), along with increasing LVDP levels and decreasing glucose levels. Therefore, EXE protects the STZ-induced diabetic myocardium injury against ischemia/ reperfusion injury.

Subjective Well-Being and It's Related Factors in Korean Rural Elderly (농촌지역 노인들의 주관적 행복감과 이에 관련하는 요인)

  • Lee, Sung-Kook;Kai, Ichiro
    • Journal of agricultural medicine and community health
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    • v.20 no.2
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    • pp.121-131
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    • 1995
  • This study aims 1) To explicate the multidimensional structure of a widely used measure of subjective well-being, the Philadelphia Geriatric Center(PGC) Morale Scale is used to measure health in elderly populations and 2) To examine the relationship between the socioeconomic status and related variables, health and physical disability and subjective well-being in elderly populations. The selection of subjects was determined through a survey of 672 rural dwelling elderly persons(269 males and 403 females) aged 60 years and over. The respondents were interviewed by 18 trained health workers using the questionnaire from July 4 to July 9 in 1994. The subjects were surveyed again during the period from August 1 to August 6 in 1994 to conform the questionnaire's reliability. Subjective well-being was evaluated using the Revised Questionnaire of the Philadelphia Geriatric Center(PGC) Moral Scale(17 items, Lawton, 1975). The results are as follows : 1) The item scores were intercorrelated and subjected to a principal component analysis. A rotated three-factor solution was done, accounting for 40.9% of the total variance. Thus, the PGC morale Scale can be derived from three stable factors : Factor 1 was explained "Lonely Dissatisfaction(7 items)", Factor 2 was explained "Agitation (5 items)", Factor 3 was explained "Attitude Towards Own Aging (5 items)". Further, these factors have a high degree of internal consistency, as determined by Cronbach's alpha : 0.7852. 2) The total mean score of PGC Morale Scale was 8.73. Sex, Age, Education, Current disease, Family type, Economic status, ADL, IADL were significantly difference in mean scores of PGC morale scale. 3) In the results of stepwise multiple regression analysis of subjective well-being. the most contributing factors were economic status, IADL, current disease, family type, sex and the R square was 0.23.

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Gynostemma pentaphyllum extract and Gypenoside L enhance skeletal muscle differentiation and mitochondrial metabolism by activating the PGC-1α pathway in C2C12 myotubes

  • Kim, Yoon Hee;Jung, Jae In;Jeon, Young Eun;Kim, So Mi;Oh, Tae Kyu;Lee, Jaesun;Moon, Joo Myung;Kim, Tae Young;Kim, Eun Ji
    • Nutrition Research and Practice
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    • v.16 no.1
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    • pp.14-32
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    • 2022
  • BACKGROUND/OBJECTIVES: Peroxisome proliferator-activated receptor-gamma co-activator-1α (PGC-1α) has a central role in regulating muscle differentiation and mitochondrial metabolism. PGC-1α stimulates muscle growth and muscle fiber remodeling, concomitantly regulating lactate and lipid metabolism and promoting oxidative metabolism. Gynostemma pentaphyllum (Thumb.) has been widely employed as a traditional herbal medicine and possesses antioxidant, anti-obesity, anti-inflammatory, hypolipemic, hypoglycemic, and anticancer properties. We investigated whether G. pentaphyllum extract (GPE) and its active compound, gypenoside L (GL), affect muscle differentiation and mitochondrial metabolism via activation of the PGC-1α pathway in murine C2C12 myoblast cells. MATERIALS/METHODS: C2C12 cells were treated with GPE and GL, and quantitative reverse transcription polymerase chain reaction and western blot were used to analyze the mRNA and protein expression levels. Myh1 was determined using immunocytochemistry. Mitochondrial reactive oxygen species generation was measured using the 2'7'-dichlorofluorescein diacetate assay. RESULTS: GPE and GL promoted the differentiation of myoblasts into myotubes and elevated mRNA and protein expression levels of Myh1 (type IIx). GPE and GL also significantly increased the mRNA expression levels of the PGC-1α gene (Ppargc1a), lactate metabolism-regulatory genes (Esrra and Mct1), adipocyte-browning gene fibronectin type III domain-containing 5 gene (Fndc5), glycogen synthase gene (Gys), and lipid metabolism gene carnitine palmitoyltransferase 1b gene (Cpt1b). Moreover, GPE and GL induced the phosphorylation of AMP-activated protein kinase, p38, sirtuin1, and deacetylated PGC-1α. We also observed that treatment with GPE and GL significantly stimulated the expression of genes associated with the anti-oxidative stress response, such as Ucp2, Ucp3, Nrf2, and Sod2. CONCLUSIONS: The results indicated that GPE and GL enhance exercise performance by promoting myotube differentiation and mitochondrial metabolism through the upregulation of PGC-1α in C2C12 skeletal muscle.

Anti-adipogenic effect of mulberry leaf ethanol extract in 3T3-L1 adipocytes

  • Yang, Soo Jin;Park, Na-Young;Lim, Yunsook
    • Nutrition Research and Practice
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    • v.8 no.6
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    • pp.613-617
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    • 2014
  • BACKGROUND/OBJECTIVES: Adipogenesis is part of the cell differentiation process in which undifferentiated fibroblasts (pre-adipocytes) become mature adipocytes with the accumulation of lipid droplets and subsequent cell morphological changes. Several transcription factors and food components have been suggested to be involved in adipogenesis. The aim of this study was to determine whether mulberry leaf ethanol extract (MLEE) affects adipogenesis in 3T3-L1 adipocytes. MATERIALS/METHODS: The 3T3-L1 adipocytes were treated with different doses of MLEE for 8 days starting 2 days post-confluence. Cell viability, fat accumulation, and adipogenesis-related factors including CCAAT-enhancer-binding protein alpha ($C/EBP{\alpha}$), peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$), $PPAR{\gamma}$ coactivator 1 alpha (PGC-$1{\alpha}$), fatty acid synthase (FAS), and adiponectin were analyzed. RESULTS: Results showed that MLEE treatments at 10, 25, 50, and $100{\mu}g/ml$ had no effect on cell morphology and viability. Without evident toxicity, all MLEE treated cells had lower fat accumulation compared with control as shown by lower absorbances of Oil Red O stain. MLEE at 50 and $100{\mu}g/ml$ significantly reduced protein levels of $PPAR{\gamma}$, PGC-$1{\alpha}$, FAS, and adiponectin in differentiated adipocytes. Furthermore, protein level of $C/EBP{\alpha}$ was significantly decreased by the treatment of $100{\mu}g/ml$ MLEE. CONCLUSION: These results demonstrate that MLEE treatment has an anti-adipogenic effect in differentiated adipocytes without toxicity, suggesting its potential as an anti-obesity therapeutic.

Inhibition of Type II Diabetes in ob/ob Mice and Enhancement of Mitochodrial Biogenesis in C2C12 Myotubes by Korean Mistletoe Extract (한국산 겨우살이 추출물(KME)의 2형 당뇨 억제 및 근육세포 미토콘드리아 생성 증가 효과)

  • Jung, Hoe-Yune;Yoo, Yung Choon;Kim, Inbo;Sung, Nak Yun;Choi, Ok-Byung;Choi, Bo-Hwa;Kim, Jong-Bae
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.3
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    • pp.324-330
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    • 2015
  • In this study, the anti-diabetic activity of a cold water extract of Korean mistletoe (KME) was investigated in C57BL/6J Lep ob (ob/ob) mice. Oral administration of KME (50 or 100 mg/kg/d) significantly inhibited the level of blood glucose of ob/ob mice after 5 days from the beginning of KME treatment. And the anti-diabetic effect of KME was stabilized 10 days after oral administration, showing a substantial reduction of blood glucose levels by more than 20% as compared with control mice. The results of oral glucose tolerance test (OGTT) revealed that oral administration of KME gave rise to a remarkable improvement in overall glucose response. Oral administration of KME in ob/ob diabetic mice also significantly reduced blood total cholesterol (TCHO) and triglyceride (TG) levels compared with the diabetic control mice. Moreover, in an in vitro experiment using C2C12 myotubes, treatment of KME prominently increased glucose uptake. Interestingly, KME significantly increased the expression of peroxisome proliferator-activated receptor gamma coactivator 1-${\alpha}$ ($PGC-1{\alpha}$), a head regulator of mitochondrial biogenesis and oxidative metabolism, and $PGC-1{\alpha}$-associated genes such as glucose transporter type 4 (GLUT4), estrogen-related receptor-${\alpha}$ ($ERR-{\alpha}$), nuclear respiratory factor-1 (NRF-1), and mitochondrial transcription factor A (TmfA) in C2C12 cells. These results suggest that KME has potential as a novel therapeutic agent for diabetes, and its anti-diabetic activity may be related to the regulation of mitochondrial biogenesis.

Anti-Obesity Effect of Schizandrae Fructus Water Extract through Regulation of AMPK/Sirt1/PGC-1α signaling pathway (AMPK/Sirt1/PGC-1α 신호 전달 경로의 조절을 통한 오미자 추출물의 비만 개선 효과)

  • Lee, Se Hui;Park, Hae-Jin;Shin, Mi-Rae;Roh, Seong-Soo
    • The Korea Journal of Herbology
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    • v.37 no.2
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    • pp.1-11
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    • 2022
  • Objectives : Although the anti-obesity effect of Schizandrae Fructus water extract has been demonstrated, its underlying mechanism is still unclear. Therefore, we aimed to evaluate the anti-obesity effect of Schizandrae Fructus water extract through the p-AMP-activated protein kinase (p-AMPK), sirtuin1 (Sirt1), and peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling in 60% high-fat diet (HFD)-induced obese mouse model. Methods : Male C57BL/6 mice were divided into four groups. The Normal group was fed a normal diet and the obese groups were fed 60% HFD. Except for the Control group, the GG group was supplemented with 0.5% Garcinia gummigutta and the SCW group was supplemented with 0.5% Schizandrae Fructus water extract. After 6 weeks, obesity-related biomarkers in serum were measured and the expressions of protein for lipid-related factors in liver tissue were analyzed by western blot. Results : Treatment with SCW significantly down-regulated body weight compared to the Control group. SCW down-regulated levels of triglyceride and total cholesterol in serum and significantly increased p-AMPK, Sirt1, and PGC-1α in liver tissue. In addition, the expressions of fatty acid oxidation-related proteins such as peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyltransferase 1A (CPT-1A), uncoupling protein 1 (UCP1), and uncoupling protein 3 (UCP3) were significantly up-regulated. However, fatty acid synthesis-related proteins including sterol regulatory element-binding protein-1 (SREBP-1), phospho-Acetyl-CoA Carboxylase (p-ACC), and fatty acid synthase (FAS) were significantly down-regulated. Conclusions : Taken together, SCW treatment showed anti-obesity effect by regulating both fatty acid oxidation-related and fatty acid synthesis-related proteins through AMPK/Sirt1/PGC-1α signaling in 60% HFD-induced obese mice.

Moderate Intensity Exercise Has More Positive Effects on The Gene Expression of Inflammasome, M1, M2 Macrophage Infiltration and Brown Adipocyte Markers Compared to High Intensity Exercise in Subcutaneous Adipose of Obese Mice Induced By High Fat Diet (비만모델에서 중강도 운동에 의한 인플라마좀, 대식세포 침윤, 갈색지방 관련 바이오 마커의 개선 효과)

  • Kim, Yong-An;Pitriani, Pipit;Park, Hee-Geun;Lee, Wang-Lok
    • Journal of Life Science
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    • v.29 no.3
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    • pp.303-310
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    • 2019
  • The purpose of the study was to compare the effect of either moderate or high intensity aerobic exercise on inflammasome, M1, M2 macrophage infiltration and brown adipocyte markers in subcutaneous adipose tissue of the high fat diet-induced obese mice. The 4 weeks male C57BL/6 mice were randomly assigned to four groups: normal diet control (NC; n=10), high-fat diet control (HC; n=10), high fat diet with moderate intensity exercise (HME; n=10), or high fat diet with high intensity exercise (HIE; n=10) groups. The high fat diet was given 60% calories from fat whereas normal diet was given 18% calories from fat. The moderate intensity exercise group (HME) was set at 10m/min in the first 2 weeks, 12m/min in 3-5 weeks and 14m/min in 6-16 weeks and the high intensity exercise group (HIE) was set at 14m/min in the first 2 weeks, 17m/min in 3-5 weeks and 18m/min in 6-16 weeks. The semi quantitative reverse transcription-polymerase chain reaction (RT PCR) was used to analyze the gene expression. The moderate intensity exercise significantly reduced the expression of NLRP3, F480, CD11c and CD86. Further, the moderate intensity exercise significantly increased CD206 and $PGC1{\alpha}$, BMP7 and PRDM. The high intensity exercise significantly reduced NLRP3, CD11c and CD86. Further, the high intensity exercise significantly increased $PGC1{\alpha}$ and BMP7. In conclusion, moderate intensity exercise has more positive effects on inflammasome, M1, M2 macrophage infiltration and brown adipocyte maskers compared to high intensity exercise in high fat diet induced obese mice.

HDAC4 Regulates Muscle Fiber Type-Specific Gene Expression Programs

  • Cohen, Todd J.;Choi, Moon-Chang;Kapur, Meghan;Lira, Vitor A.;Yan, Zhen;Yao, Tso-Pang
    • Molecules and Cells
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    • v.38 no.4
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    • pp.343-348
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    • 2015
  • Fiber type-specific programs controlled by the transcription factor MEF2 dictate muscle functionality. Here, we show that HDAC4, a potent MEF2 inhibitor, is predominantly localized to the nuclei in fast/glycolytic fibers in contrast to the sarcoplasm in slow/oxidative fibers. The cytoplasmic localization is associated with HDAC4 hyper-phosphorylation in slow/oxidative-fibers. Genetic reprogramming of fast/glycolytic fibers to oxidative fibers by active CaMKII or calcineurin leads to increased HDAC4 phosphorylation, HDAC4 nuclear export, and an increase in markers associated with oxidative fibers. Indeed, HDAC4 represses the MEF2-dependent, PGC-$1{\alpha}$-mediated oxidative metabolic gene program. Thus differential phosphorylation and localization of HDAC4 contributes to establishing fiber type-specific transcriptional programs.

NecroX-5 protects mitochondrial oxidative phosphorylation capacity and preserves PGC1α expression levels during hypoxia/reoxygenation injury

  • Vu, Thi Thu;Kim, Hyoung Kyu;Le, Thanh Long;Nyamaa, Bayalagmaa;Song, In-Sung;To, Thanh Thuy;Nguyen, Quang Huy;Marquez, Jubert;Kim, Soon Ha;Kim, Nari;Ko, Kyung Soo;Rhee, Byoung Doo;Han, Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.2
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    • pp.201-211
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    • 2016
  • Although the antioxidant and cardioprotective effects of NecroX-5 on various in vitro and in vivo models have been demonstrated, the action of this compound on the mitochondrial oxidative phosphorylation system remains unclear. Here we verify the role of NecroX-5 in protecting mitochondrial oxidative phosphorylation capacity during hypoxia-reoxygenation (HR). Necrox-5 treatment ($10{\mu}M$) and non-treatment were employed on isolated rat hearts during hypoxia/reoxygenation treatment using an ex vivo Langendorff system. Proteomic analysis was performed using liquid chromatography-mass spectrometry (LC-MS) and non-labeling peptide count protein quantification. Real-time PCR, western blot, citrate synthases and mitochondrial complex activity assays were then performed to assess heart function. Treatment with NecroX-5 during hypoxia significantly preserved electron transport chain proteins involved in oxidative phosphorylation and metabolic functions. NecroX-5 also improved mitochondrial complex I, II, and V function. Additionally, markedly higher peroxisome proliferator-activated receptor-gamma coactivator-$1{\alpha}$ ($PGC1{\alpha}$) expression levels were observed in NecroX-5-treated rat hearts. These novel results provide convincing evidence for the role of NecroX-5 in protecting mitochondrial oxidative phosphorylation capacity and in preserving $PGC1{\alpha}$ during cardiac HR injuries.

Gene Expression Pattern during Early Embryogenesis and Transcriptional Activities of Estrogen Receptor-Related Receptor(ERR) in Sea Urchin, Strongylocentrotus nudus (둥근성게(Strongylocentrotus nudus) Estrogen Receptor-Related Receptor(ERR)의 초기 발생시 유전자 발현 패턴과 전사 활성)

  • Maeng, Se-Jung;Kim, Mi-Soon;Sohn, Young-Chang
    • Development and Reproduction
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    • v.13 no.4
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    • pp.249-256
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    • 2009
  • The estrogen receptor-related receptors (ERRs) are a group of nuclear receptor superfamily of transcription factors. ERRs and estrogen receptors (ERs) have overlapping affinities for coactivators and DNA binding sites, but differ markedly in ligand binding and activation. The three mammalian ERR genes have been implicated in diverse physiological processes ranging from placental development to maintenance of bone density, whereas the molecular diversity, function, and regulation of ERRs in non-mammalian species are not well understood. In the present study, to investigate the involvement of ERR in transcription and embryogenesis in marine invertebrates, a cDNA encoding ERR (SnERR) was cloned from the gonad in Strongylocentrotus nudus, by polymerase chain reaction (PCR). The amino acid sequence of SnERR showed high homology with that of S. purpuratus (91%). A phylogenetic tree clearly showed that SnERR is a member of the ERR family and clustered in echinodermata group as supported by a high bootstrap value. We examined gene expression of SnERR during embryonic development of S. nudus using real-time PCR. During the embryonic development, the mRNA of ERR was significantly high levels in early development stages (4~64 cell) and larval stages. The SnERR slightly activated transcription through the classical estrogen response elements (EREs) in the presence of genistein. In addition, peroxisome proliferator-activated receptor $\gamma$ coactivator (PGC)-$1\alpha$ knwon as a coactivator of ERR enhanced the snERR-mediated transactivation, suggesting that the PGC-$1\alpha$ is a coactivator of SnERR.

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