• 한국응용과학기술학회지
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• 제37권4호
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• pp.744-754
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• 2020

본 연구는 파킨슨 질환(Parkinson's disease) 마우스 모델을 대상으로 지구성 운동과 MitoQ 섭취가 뇌의 흑질의 미토콘드리아 기능에 미치는 영향을 확인하는데 목적이 있다. 파킨슨 질환을 유도하기 위해 C57BL/6 수컷 마우스를 대상으로 복강 내 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) 25mg/kg과 흡수를 돕기 위한 probenecid 250mg/kg을 이용하여 주 2회 5주간 총 10회 투여하였다. 실험 집단은 생리식염수를 투여하는 집단(Normal Conrol (NC), n=10), MPTP 투여집단(MPTP Control (MC), n=10), MPTP 투여 + MitoQ 투여집단(MPTP + MitoQ (MQ), n=10), MPTP 투여 + 운동집단(MPTP + Exercise (ME), n=10), MPTP 투여 + MitoQ 투여 + 운동집단(MPTP + MitoQ + Exercise (MQE), n=10) 총 5 집단으로 구성하였으며, 운동집단은 지구성 운동을 실시하였고 MitoQ집단은 점진적으로 250μmol로 늘리면서 5주간 섭취하였다. 연구결과 Rotarod-test에서 MC 집단에 비해 처치 집단은 운동 기능 저하의 개선을 보였다. 또한 MC 집단에 비해 처치 집단은 tyrosine hydroxylase의 수준의 증가와 알파시누클린(α-synuclein) 단백질 축적을 감소시켰다. 그리고 미토콘드리아 생합성에 주요조절 인자인 PGC-1α와 항산화 효소인 Catalase 발현이 MC 집단에 비해 처치 집단에서 증가해 미토콘드리아 기능을 개선했으며, 세포사멸 조절인자인 Bcl-2의 증가와 Bax의 감소를 통해 세포사멸을 완화했다. 따라서 5주간의 지구성 운동과 MitoQ 섭취는 파킨슨 질환에서 나타나는 병리학적 특징을 완화하고 운동기능을 향상시키는데 효과적인 것으로 나타났다.

• Kidney Research and Clinical Practice
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• 제35권2호
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• pp.69-77
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• 2016

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, and its pathogenesis is complex and has not yet been fully elucidated. Abnormal glucose and lipid metabolism is key to understanding the pathogenesis of DN, which can develop in both type 1 and type 2 diabetes. A hallmark of this disease is the accumulation of glucose and lipids in renal cells, resulting in oxidative and endoplasmic reticulum stress, intracellular hypoxia, and inflammation, eventually leading to glomerulosclerosis and interstitial fibrosis. There is a growing body of evidence demonstrating that dysregulation of 50 adenosine monophosphate-activated protein kinase (AMPK), an enzyme that plays a principal role in cell growth and cellular energy homeostasis, in relevant tissues is a key component of the development of metabolic syndrome and type 2 diabetes mellitus; thus, targeting this enzyme may ameliorate some pathologic features of this disease. AMPK regulates the coordination of anabolic processes, with its activation proven to improve glucose and lipid homeostasis in insulin-resistant animal models, as well as demonstrating mitochondrial biogenesis and antitumor activity. In this review, we discuss new findings regarding the role of AMPK in the pathogenesis of DN and offer suggestions for feasible clinical use and future studies of the role of AMPK activators in this disorder.

• Journal of Microbiology and Biotechnology
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• 제31권5호
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• pp.676-685
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• 2021

RNA-binding proteins are involved in RNA metabolism and posttranscriptional regulation of various fundamental biological processes. The PUF family of RNA-binding proteins is highly conserved in eukaryotes, and its members regulate gene expression, mitochondrial biogenesis, and RNA processing. However, their biological functions in Aspergillus species remain mostly unknown in filamentous fungi. Here we have characterized the puf genes in the model organism Aspergillus nidulans. We generated deletion mutant strains for the five putative puf genes present in the A. nidulans genome and investigated their developmental phenotypes. Deletion of pufA or pufE affected fungal growth and asexual development. pufA mutants exhibited decreased production of asexual spores and reduced mRNA expression of genes regulating asexual development. The pufE deletion reduced colony growth, increased formation of asexual spores, and delayed production of sexual fruiting bodies. In addition, the absence of pufE reduced both sterigmatocystin production and the mRNA levels of genes in the sterigmatocystin cluster. Finally, pufE deletion mutants showed reduced trehalose production and lower resistance to thermal stress. Overall, these results demonstrate that PufA and PufE play roles in the development and sterigmatocystin metabolism in A. nidulans.

• 대한의생명과학회지
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• 제27권1호
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• pp.12-18
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• 2021

Hypertension (HTN) is one of the cardiovascular disease risk factors. Peroxisome proliferator-activated receptor γ coactivator 1 alpha (PPARGC1A) is involved in a master modulator of mitochondrial biogenesis, and pulmonary arterial hypertension. In this study, we report results of PPARGC1A were associated with hypertension and its intermediate phenotype of systolic (SBP) and diastolic blood pressure (DBP) in the Korean population. In detail, identifying a susceptibility locus, 3 SNPs for HTN, 2 SNPs for SBP, 3 SNPs for DBP at P<0.05. Among them, rs1472095 in PPARGC1A gene statistically demonstrated one of the significant correlations with Hypertension (P-value=0.00359, OR=0.8, 95% CI=0.68~0.93). The minor allele (T) of PPARGC1A was statistically associated with the increased value of DBP, SBP, and the increase risk of hypertension. We aim to manifest a significant association between genetic variant in PPARGC1A and hypertension. This finding suggested that association of PPARGC1A genetic polymorphism and HTN accelerates our understanding of blood pressure control and underlines potential drug targets for treatment of hypertension.

• Journal of Microbiology and Biotechnology
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• 제33권10호
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• pp.1268-1280
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• 2023

Echinacoside (ECH) is a naturally occurring phenylethanoid glycoside, isolated from Echinacea angustifolia, and this study aimed to analyze its effect on thermogenesis and its interaction with dopaminergic receptors 1 and 5 (DRD1 and DRD5) in 3T3-L1 white adipocytes and mice models. We employed RT-PCR, immunoblot, immunofluorescence, a staining method, and an assay kit to determine its impact. ECH showed a substantial increase in browning signals in vitro and a decrease in adipogenic signals in vivo. Additionally, analysis of the iWAT showed that the key genes involved in beiging, mitochondrial biogenesis, and ATP-dependent thermogenesis were upregulated while adipogenesis and lipogenesis genes were downregulated. OXPHOS complexes, Ca²⁺ signaling proteins as well as intracellular Ca²⁺ levelswere also upregulated in 3T3-L1 adipocytes following ECH treatment. This was collectively explained by mechanistic studies which showed that ECH mediated the beiging process via the DRD1/5-cAMP-PKA and subsequent downstream molecules, whereas it co-mediated the α1-AR-signaling thermogenesis via the DRD1/5/SERCA2b/RyR2/CKmt pathway in 3T3-L1 adipocytes. Animal experiments revealed that there was a 12.28% reduction in body weight gain after the ECH treatment for six weeks. The effects of ECH treatment on adipose tissue can offer more insights into the treatment of obesity and metabolic syndrome.

• Preventive Nutrition and Food Science
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• 제21권1호
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• pp.62-67
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• 2016

Green tea (Camellia sinensis) is one of the most popular beverages in the world and has been acknowledged for centuries as having significant health benefits. (-)-Epigallocatechin-3-gallate (EGCG) is the most abundant catechin in green tea, and it has been reported to have health benefit effects. Peroxisome proliferator-activated receptor ${\gamma}$ coactivator $(PGC)-1{\alpha}$ is a crucial regulator of mitochondrial biogenesis and hepatic gluconeogenesis. The objective of this study was to investigate whether EGCG from green tea can affect the ability of transcriptional regulation on $PGC-1{\alpha}$ mRNA expression in HepG2 cells and 3T3-L1 adipocytes. To study the molecular mechanism that allows EGCG to control $PGC-1{\alpha}$ expression, the promoter activity levels of $PGC-1{\alpha}$ were examined. The $PGC-1{\alpha}$ mRNA level was measured using quantitative real-time PCR. The -970/+412 bp of $PGC-1{\alpha}$ promoter was subcloned into the pGL3-Basic vector that includes luciferase as a reporter gene. EGCG was found to up-regulate the $PGC-1{\alpha}$ mRNA levels significantly with $10{\mu}mol/L$ of EGCG in HepG2 cells and differentiated 3T3-L1 adipocytes. $PGC-1{\alpha}$ promoter activity was also increased by treatment with $10{\mu}mol/L$ of EGCG in both cells. These results suggest that EGCG may induce $PGC-1{\alpha}$ gene expression, potentially through promoter activation.

• 한국초지조사료학회지
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• 제36권3호
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• pp.237-242
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• 2016

Copper (Cu) is a necessary microelement for plants. However, high concentrations of Cu are toxic to plants that change the regulation of several stress-induced proteins. In this study, an annealing control primer (ACP) based approach was used to identify differentially expressed Cu-induced genes in alfalfa leaves. Two-week-old alfalfa plants (Medicago sativa L.) were exposed to Cu for 6 h. Total RNAs were isolated from treated and control leaves followed by ACP-based PCR technique. Using GeneFishing ACPs, we obtained several genes those expression levels were induced by Cu. Finally, we identified several genes including UDP-glucuronic acid decarboxylase, transmembrane protein, small heat shock protein, C-type cytochrome biogenesis protein, mitochondrial 2-oxoglutarate, and trans-2,3-enoyl-CoA reductase in alfalfa leaves. These identified genes have putative functions in cellular processes such as cell wall structural rearrangements, transduction, stress tolerance, heme transport, carbon and nitrogen assimilation, and lipid biosynthesis. Response of Cu-induced genes and their identification in alfalfa would be useful for molecular breeding to improve alfalfa with tolerance to heavy metals.

• BMB Reports
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• 제51권4호
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• pp.200-205
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• 2018

Exercise and resveratrol supplementation exhibit anti-obesity functions in the long term but have not been fully investigated yet in terms of their early potential effectiveness. Mice fed with high-fat diet were categorized into control (Cont), exercise (Ex), resveratrol supplementation (Res), and exercise combined with resveratrol supplementation (Ex + Res) groups. In the four-week period of weight loss, exercise combined with resveratrol supplementation exerted no additional effects on body weight loss but significantly improved whole-body glucose and lipid homeostasis. The combined treatment significantly decreased intrahepatic lipid content but did not affect intramyocellular lipid content. Moreover, the treatment significantly increased the contents of mtDNA and cytochrome c, the expression levels of peroxisome proliferator-activated receptor gamma coactivator-1 alpha and its downstream transcription factors, and the activities of ATPase and citrate synthase. However, exercise, resveratrol, and their combination did not promote myofiber specification toward slow-twitch type. The effects of exercise combined with resveratrol supplementation on weight loss could be partly due to enhanced mitochondrial biogenesis and not to fiber-type shift in skeletal muscle tissues.

• 한방재활의학과학회지
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• 제29권4호
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• pp.15-27
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• 2019

Objectives This study was performed to evaluate anti-obesity effects of Crataegus pinnatifida (CP) on high-fat-diet induced obese mice. Methods The experimental animals were divided into four groups: normal diet (NOR) group, high fat diet (HFD) group, HFD+Xenical (XEN) group, and HFD+CP (CP) group. NOR group was fed a normal diet and the other three groups were fed high fat diet during the experiment. After the first two weeks of diet, XEN group and CP group were administered with XEN or CP for seven weeks, respectively. After that, we measured body weight, liver weight, fat weight, food intake, and serum concentrations of lipids and liver enzymes. Also the liver, intestine, fat tissue was removed to estimate the obesity-related mRNA expressions and the stool sample was collected to analyze the gut microbiota. Results We found that body weight, fat weight, and triglyceride level were decreased significantly in CP group compared to HFD group. Also CP significantly suppressed gene expressions associated with lipogenesis and inflammation, and increased gene expressions of browning of white adipose tissue and mitochondrial biogenesis. Moreover, it shifted the microbial diversity closer to that of NOR group and increased Firmicutes/Bacteriodetes ratio. Conclusions These results suggest that CP decrease body weight, fat weight and serum triglyceride. Also it inhibit inflammation and adipogenesis, altering gut microbial diversity and abundance. In conclusion, CP could be used as a therapeutic drug for obesity via gut microbiota modulation.

• Journal of Ginseng Research
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• 제46권3호
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• pp.454-463
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• 2022

Background: Gintonin-enriched fraction (GEF), a non-saponin fraction of ginseng, is a novel glycolipoprotein rich in hydrophobic amino acids. GEF has recently been shown to regulate lipid metabolism and browning in adipocytes; however, the mechanisms underlying its effects on energy metabolism and whether it affects sarcopenic obesity are unclear. We aimed to evaluate the effects of GEF on skeletal muscle atrophy in high-fat diet (HFD)-induced obese mice. Methods: To examine the effect of GEF on sarcopenic obesity, 4-week-old male ICR mice were used. The mice were divided into four groups: chow diet (CD), HFD, HFD supplemented with 50 mg/kg/day GEF, or 150 mg/kg/day GEF for 6 weeks. We analyzed body mass gain and grip strength, histological staining, western blot analysis, and immunofluorescence to quantify changes in sarcopenic obesity-related factors. Results: GEF inhibited body mass gain while HFD-fed mice gained 22.7 ± 2.0 g, whereas GEF-treated mice gained 14.3 ± 1.2 g for GEF50 and 11.8 ± 1.6 g for GEF150 by downregulating adipogenesis and inducing lipolysis and browning in white adipose tissue (WAT). GEF also enhanced mitochondrial biogenesis threefold in skeletal muscle. Furthermore, GEF-treated skeletal muscle exhibited decreased expression of muscle-specific atrophic genes, and promoted myogenic differentiation and increased muscle mass and strength in a dose-dependent manner (p < 0.05). Conclusion: These findings indicate that GEF may have potential uses in preventing sarcopenic obesity by promoting energy expenditure and attenuating skeletal muscle atrophy.