• Journal of Nutrition and Health
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• 제37권9호
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• pp.786-793
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• 2004

Women with menopause or rats with ovariectomy is associated with increased body weight, body fat and insulin resistance, which are components of metabolic syndrome. Increased prevalence of metabolic syndrome after menopause might be associated with mitochondrial dysfunction, since mitochondrial oxidative and phosphorylation activity is strongly correlated with insulin sensitivity. Although estradiol replacement prevents the metabolic syndrome, harmful effect of estradiol hampers the casual usage to prevent the metabolic syndrome. It has been reported that genistein has a mild estrogenic activity, decreases fat mass in mice and has an antidiabetic role in diabetic rats. Although insulin resistance is closely related to mitochondrial functions, there has not been yet any study in regard to the effect of dietary genistein on mitochondrial function in the insulin resistant female subjects induced by ovariectomy or similar situation. The present study investigated whether the supplementation of genistein in the high fat diet affected the mitochondrial function of high fat fed ovariectomized rats. Female Sprague Dawley rats (8 weeks old) were assigned to the following groups: sham-operated+ high fat diet (S, n=6); sham-operated + high fat diet with 0.1% genistein (S + G, n=7); ovariectomized + high fat diet (OVX, n=8); ovariectomized + high fat diet with 0.1% genistein (OVX+ G, n=8). Ovariectomy significantly increased body weight compared with S group. Genistein consumption in ovariectomized (OVX + G) rats decreased body weight gain compared with OVX rats. Liver weights were increased by ovariectomy. The hepatic mitochondrial protein density expressed as mg per g liver was lower in the OVX group than in the S group. However, OVX + G group showed the increased mitochondrial protein density similar to the level of S group. When mRNA levels of genes related to mitochondria such as peroxisome proliferator-activated receptor ${\gamma}$ coactivator 1 (PGC-1) and cytochrome c oxidase subunit III (COX III) were measured, there were decreases in the mRNA levels of PGC-1 and COX III in S + G, OVX and OVX + G group. The activity of cytochrome c oxidase was not different between groups. We could observe the decrease in succinate dehydrogenase (SDH) activity per g liver in OVX rats. Genistein supplement increased SDH activity. In conclusion, genistein supplementation to the OVX rats enhanced mitochondrial function by increasing mitochondrial protein density and SDH activity. The improvement in mitochondrial function by genistein can contribute to the improvement in metabolic syndrome.

• 한국균학회지
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• 제20권1호
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• pp.51-57
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• 1992

Mitochondria in Pleurotus ostreatus were isolated and purified by stepped sucrose density gradient centrifugation, to compare the effects of organic compound on the activities of mitochondrial ATPase in Basidiomycotina with those in mammalian cell. The effects of N, N'-dicycio-hexylcarbodiimide (DCCD), carbonyl cyanide m-chlorophenylhydrazone (CCCP), sodium azide and aurovertin known as compounds to be related to electron transfer system in mitochondria were studied. A activity of mitochondrial ATPase was inhibited by 64%, 57% and 53% in the presence of 0.25 mM DCCD, 0.02 mM sodium azide and 1.5 $({\mu}g/mg\;of\;protein)$ aurovertin B, respectively. It was stimulated by 22% in the presence of 0.15 ${\mu}M$ CCCP.

• Journal of Yeungnam Medical Science
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• 제34권2호
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• pp.174-181
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• 2017

Ferroptosis is a newly recognized type of cell death that results from iron-dependent lipid peroxidation and is different from other types of cell death, such as apoptosis, necrosis, and autophagic cell death. This type of cell death is characterized by mitochondrial shrinkage with an increased mitochondrial membrane density and outer mitochondrial membrane rupture. Ferroptosis can be induced by a loss of activity of system $X_c{^-}$ and the inhibition of glutathione peroxidase 4, followed by the accumulation of lipid reactive oxygen species (ROS). In addition, inactivation of the mevalonate and transsulfuration pathways is involved in the induction of ferroptosis. Moreover, nicotinamide adenine dinucleotide phosphate oxidase and p53 promote ferroptosis by increasing ROS production, while heat shock protein beta-1 and nuclear factor erythroid 2-related factor 2 inhibit ferroptosis by reducing iron uptake. This article outlines the molecular mechanisms and signaling pathways of ferroptosis regulation, and explains the roles of ferroptosis in human disease.

• Journal of Ginseng Research
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• 제43권1호
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• pp.95-104
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• 2019

Background: Oxidized low-density lipoprotein (ox-LDL) causes vascular endothelial cell inflammatory response and apoptosis and plays an important role in the development and progression of atherosclerosis. Ginsenoside compound K (CK), a metabolite produced by the hydrolysis of ginsenoside Rb1, possesses strong anti-inflammatory effects. However, whether or not CK protects ox-LDL-damaged endothelial cells and the potential mechanisms have not been elucidated. Methods: In our study, cell viability was tested using a 3-(4, 5-dimethylthiazol-2yl-)-2,5-diphenyl tetrazolium bromide (MTT) assay. Expression levels of interleukin-6, monocyte chemoattractant protein-1, tumor necrosis factor-${\alpha}$, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 were determined by enzyme-linked immunosorbent assay and Western blotting. Mitochondrial membrane potential (${\Delta}{\Psi}m$) was detected using JC-1. The cell apoptotic percentage was measured by the Annexin V/ propidium iodide (PI) assay, lactate dehydrogenase, and caspase-3 expression. Apoptosis-related proteins, nuclear factor $(NF)-{\kappa}B$, and mitogen-activated protein kinases (MAPK) signaling pathways protein expression were quantified by Western blotting. Results: Our results demonstrated that CK could ameliorate ox-LDL-induced human umbilical vein endothelial cells (HUVECs) inflammation and apoptosis, $NF-{\kappa}B$ nuclear translocation, and the phosphorylation of p38 and c-Jun N-terminal kinase (JNK). Moreover, anisomycin, an activator of p38 and JNK, significantly abolished the anti-apoptotic effects of CK. Conclusion: These results demonstrate that CK prevents ox-LDL-induced HUVECs inflammation and apoptosis through inhibiting the $NF-{\kappa}B$, p38, and JNK MAPK signaling pathways. Thus, CK is a candidate drug for atherosclerosis treatment.

• 한국식품과학회지
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• 제49권6호
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• pp.685-692
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• 2017

극심한 스트레스, 서구화된 식습관, 불규칙한 생활리듬 등에 의한 부족한 신체활동은 체력을 약화시키고 비만, 당뇨, 고혈압, 우울증, 근감소증 등을 야기한다. 본 연구에서는 ARC가 운동능력 증진에 미치는 효능을 세포 및 동물실험을 통해 검증하였다. ARC를 처리함에 따라 근육 세포 내에서 p-AMPK와 SIRT1 단백질, PGC-$1{\alpha}$, NFR1, TFAM mRNA 발현양과 미토콘드리아 양이 증가하였다. 세포실험에서 ARC는 RGE와 AE단독으로 처리에 비해 ATP 생성을 더 많이 하였으며, 동물실험에서도 RGE군과 AE군에 비해 ARC군에서 운동수행능력이 더 향상시켰다. 세포 실험과 마찬가지로 ARC는 동물의 근육 조직 내에서 미토콘드리아 생합성에 관련된 유전자의 발현을 증가시켰으며, 젖산 발생량 감소 및 산화스트레스 억제로 인해 운동으로 인한 피로를 쉽게 회복시켰다. 따라서, 신선초와 홍삼 복합물에 대한 인체수준에서 과학적인 증거 및 안전성이 확보될 경우, 운동수행능력 향상을 위한 기능성 소재로서의 산업적인 활용이 확대될 것으로 기대된다.

• Nutrition Research and Practice
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• 제6권6호
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• pp.513-519
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• 2012

Aged garlic extract (AGE) is known to have a protective effect against immune system, endothelial function, oxidative stress and inflammation. We examined the effects of exercise with and without aged garlic extract administration on body weight, lipid profiles, inflammatory cytokines, and oxidative stress marker in high-fat diet (HFD)-induced obese rats. Forty-five Sprague-Dawley rats were fed either a HFD (HFD, n = 40) or a normal diet (ND, n = 5) for 6 weeks and thereafter randomized into ND (n = 5), HFD (n = 10), HFD with AGE (n = 10), HFD with Exercise (n = 10), or HFD with Exercise+AGE (n = 10) for 4 weeks. AGE groups were administered at a dose of 2.86 g/kg body weight, orally. Exercise consisted of running 15-60 min 5 days/week with gradually increasing intensity. AGE (P<0.01), Exercise, and Exercise+AGE (P<0.001) attenuated body weight gain and food efficiency ratio compared to HFD. Visceral fat and liver weight gain were attenuated (P<0.05) with all three interventions with a greater effect on visceral fat in the Exercise+AGE than AGE (P<0.001). In reducing visceral fat (P<0.001), epididymal fat (P<0.01) and liver weight (P<0.001), Exercise+AGE was effective, but exercise showed a stronger suppressive effect than AGE. Exercise+AGE showed further additive effects on reducing visceral fat and liver weight (P<0.001). AGE significantly attenuated the increase in total cholesterol and low-density lipoprotein-cholesterol compared with HFD (P<0.05). Exercise+AGE attenuated the increase in triglycerides compared with HFD (P<0.05). Exercise group significantly decrease in C-reactive protein (P<0.001). These results suggest that AGE supplementation and exercise alone have anti-obesity, cholesterol lowering, and anti-inflammatory effects, but the combined intervention is more effective in reducing weight gain and triglycerides levels than either intervention alone.

• 동의생리병리학회지
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• 제20권2호
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• pp.358-364
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• 2006

To investigate the possible mechanism of Drynariae Rhizoma extracts as a candidate of anti-cancer drug, I examined the effects of Drynariae Rhizoma extracts on the apoptosis of U937 cell line. MTT assay, flow cytometric analysis, SDS-polyacrylamide gel electrophoresis, Western blot analysis, and RT-PCR were performed. Drynariae Rhizoma extracts treatment reduced the cell viablilty of U937 cells in a dose-dependent manner, which was associated with induction of apoptotic cell death. Drynariae Rhizoma extracts treatment also reduced the levels of Bcl-xL anti-apoptotic protein expression and increased the levels of caspase-3, p53, pro-apoptotic protein, in U937 cells. RT-PCR data revealed that the level of bcl-2, bcl-xL mRNA expressions decreased in a dose-dependent manner. These findings suggest that Drynariae Rhizoma extracts may have induction of apoptotic cell death via regulation of several growth regulatory gene products. The abbreviations used are: FBS, fetal bovine serum; PBS, phosphate buffered saline; PI, propidium iodide; OD, optical density; DiOC6, 3,3-dihexyloxa carbcyanine iodide; MTT, 3 [4-5-dimethylthiazol-2-yl] -2-diphenyltetrazolium bromide.

• 한국동물학회지
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• 제31권1호
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• pp.62-70
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• 1988

미토콘드리아가 포함하고있는 결정한유물의 미새구조와 면역황금표식법에 의한 분석을 위하여 우심근 세포의 미토콘드리아에서 전자전달체에 관여하는 효소를 분리하였다. 우심근 미토콘드리아에서 분리된 효소는 실험토끼에 주사하여 (복합체I,NADH-conezyme Q reductase; 복합체 III,Ubiquinol-cytochrome-c-oxldoreductase; 복합체 IV, Cytochrome-c-oxidase)들에 대한 면역항체를 얻었다. 이들 면역항체들은 우심근과 정상인의 골격근 미토콘드리아와 미토콘드리아에 결정함유물을 포함하는 mitochondrical myopathy환자의 골격근 미토콘드리아에 반응시켜 황금입자를 표식하고 전자현미경을 이용하여 이들 면역항체반응을 관찰하였다. 미토콘드리아가 포함하는 결정함유물의 미세구조에는 paracrystalline inclusions body와 multilamellar strudure inclusion body그리고 구형결정함유물(globular crystalline inclusions body) 및 윤형구조 (whirl shaped structure)의 크리스테 중심에 있는 구형결정함유물 등의 4종류로관찰되었다. 복합체 I,복합체 Iv의 효소에 대한 항체를 우심근과 정상인 골격근 그리고 mitochondrical myopathy환자의 골격근에 동일한 면역반응을 시켰을때 미토콘드리아 크리스테에 부착하는 황금입자의 표식 정도는 각각의 근조직에서 유사한 반응이 관찰되었다. 복합체 III의 효소에 대한 항체는 우심근과 정상인의 골격근에서는 유사한 반응이 나타났으나 mitochondrical myopathy환자의 골격근에서는 극히 소수의 황금입자가 관찰되었다. 구형결정함유물은 복합체 I,III,IV의 3종류의 효소에 대한 면역반응 결과 황금입자표식은 관찰되지 않았다. 따라서 mitochondrical myopathy환자의 미토콘드리아에는 복합에 III의 효소가 결핍되었으며 구형결정함유물은 전자전달체 효소들인 복합체 I,III,Iv 효소단백질과는 상관없는 물질로 생각된다.

• Journal of Microbiology and Biotechnology
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• 제32권9호
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• pp.1154-1167
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• 2022

In this study, we investigated the anti-amnesic effect of Korean red pine (Pinus densiflora) bark extract (KRPBE) against amyloid beta_1-42 (Aβ_1-42)-induced neurotoxicity. We found that treatment with KRPBE improved the behavioral function in Aβ-induced mice, and also boosted the antioxidant system in mice by decreasing malondialdehyde (MDA) content, increasing superoxide dismutase (SOD) activities, and reducing glutathione (GSH) levels. In addition, KRPBE improved the cholinergic system by suppressing reduced acetylcholine (ACh) content while also activating acetylcholinesterase (AChE), regulating the expression of choline acetyltransferase (ChAT), postsynaptic density protein-95 (PSD-95), and synaptophysin. KRPBE also showed an ameliorating effect on cerebral mitochondrial deficit by regulating reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and ATP levels. Moreover, KRPBE modulated the expression levels of neurotoxicity indicators Aβ and phosphorylated tau (p-tau) and inflammatory cytokines TNF-α, p-IκB-α, and IL-1β. Furthermore, we found that KRPBE improved the expression levels of neuronal apoptosis-related markers BAX and BCl-2 and increased the expression levels of BDNF and p-CREB. Therefore, this study suggests that KRPBE treatment has an anti-amnestic effect by modulating cholinergic system dysfunction and neuroinflammation in Aβ_1-42-induced cognitive impairment in mice.

• Asian-Australasian Journal of Animal Sciences
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• 제28권1호
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• pp.127-134
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• 2015

Castration induces the accumulation of body fat and deposition of intramuscular fat in Korean cattle, resulting in improved beef quality. However, little is known about the metabolic adaptations in the liver following castration. To understand changes in lipid metabolism following castration, hepatic expression levels of lipid metabolism genes were compared between Korean bulls and steers. Steers had higher (p<0.001) hepatic lipids contents and higher (p<0.01) mRNA levels of lipogenic acetyl-CoA carboxylase. This differential gene expression may, in part, contribute to increased hepatic lipid content following the castration of bulls. However, we found no differences in the hepatic expression levels of genes related to triglyceride synthesis (mitochondrial glycerol-3-phosphate acyltransferase, diacylglycerol O-acyltransferase 1 and 2) and fatty acid (FA) oxidation (carnitine palmitoyltransferase 1A, C-4 to C-12 straight chain acyl-CoA dehydrogenase, very long chain acyl-CoA dehydrogenase) between bulls and steers. No differences in gene expression for very-low-density lipoprotein (VLDL) secretion, including apolipoprotein B mRNA and microsomal triglyceride transfer protein (MTTP) protein, were observed in the liver although MTTP mRNA levels were higher in steers compared to bulls. In conclusion, FA synthesis may contribute to increased hepatic lipid deposition in steers following castration. However, hepatic lipid metabolism, including triglyceride synthesis, FA oxidation, and VLDL secretion, was not significantly altered by castration. Our results suggest that hepatic lipid metabolism does not significantly contribute to increased body fat deposition in steers following castration.