• Title/Summary/Keyword: oxidative metabolism

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Tumor bioenergetics: An emerging avenue for cancer metabolism targeted therapy

  • Kee, Hyun Jung;Cheong, Jae-Ho
    • BMB Reports
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    • v.47 no.3
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    • pp.158-166
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    • 2014
  • Cell proliferation is a delicately regulated process that couples growth signals and metabolic demands to produce daughter cells. Interestingly, the proliferation of tumor cells immensely depends on glycolysis, the Warburg effect, to ensure a sufficient amount of metabolic flux and bioenergetics for macromolecule synthesis and cell division. This unique metabolic derangement would provide an opportunity for developing cancer therapeutic strategy, particularly when other diverse anti-cancer treatments have been proved ineffective in achieving durable response, largely due to the emergence of resistance. Recent advances in deeper understanding of cancer metabolism usher in new horizons of the next generation strategy for cancer therapy. Here, we discuss the focused review of cancer energy metabolism, and the therapeutic exploitation of glycolysis and OXPHOS as a novel anti-cancer strategy, with particular emphasis on the promise of this approach, among other cancer metabolism targeted therapies that reveal unexpected complexity and context-dependent metabolic adaptability, complicating the development of effective strategies.

Cholesterol-lowering Efficacy of Unrefined Bran Oil from the Pigmented Black Rice (Oryza sativa L cv. Suwon 415) in Hypercholesterolemic Rats

  • Nam, Yean-Ju;Nam, Seok-Hyun;Kang, Mi-Young
    • Food Science and Biotechnology
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    • v.17 no.3
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    • pp.457-463
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    • 2008
  • The effects of dietary supplementation of the unrefined rice bran oil from 'Suwon 415' pigmented black rice (BRBO) on cholesterol metabolism and cellular antioxidant status were investigated in hypercholesterolemic rats. The significant reduction of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) concentrations was observed in the plasma of rats fed BRBO. BRBO also decreased plasma and hepatic oxidative stress as a result of increased levels of hepatic thiobarbituric acid reactive substances (TBARS) levels associated with the elevations of hepatic superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities together with increased plasma level of tocopherol. This study indicates that dietary BRBO supplement can leads to the improvement of overall cholesterol metabolism and antioxidant status even more effectively than 'Chuchung' white rice (WRBO). Consumption of BRBO may also protect the liver from oxidative damage caused by lipid peroxidation.

Potential roles of reactive oxygen species derived from chemical substances involved in cancer development in the female reproductive system

  • Kim, Soo-Min;Hwang, Kyung-A;Choi, Kyung-Chul
    • BMB Reports
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    • v.51 no.11
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    • pp.557-562
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    • 2018
  • Reactive oxygen species (ROS) are major sources of cellular oxidative stress. Specifically, cancer cells harbor genetic alterations that promote a continuous and elevated production of ROS. While such oxidative stress conditions could be harmful to normal cells, they facilitate cancer cell growth in multiple ways by causing DNA damage and genomic instability, and ultimately by reprogramming cancer cell metabolism. This review provides up to date findings regarding the roles of ROS generation induced by diverse biological molecules and chemicals in representative women's cancer. Specifically, we describe the cellular signaling pathways that regulate direct or indirect interactions between ROS homeostasis and metabolism within female genital cancer cells.

Rh2-enriched Korean Ginseng Ameliorates Chronic Fatigue in a Forced Exercise mouse model

  • Kim, Won-Yong;Lee, Jin-Seok;Yoo, Hwa-Seung;Son, Chang-Gue
    • The Journal of Korean Medicine
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    • v.37 no.2
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    • pp.76-84
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    • 2016
  • Objectives: We evaluated the anti-fatigue effects of Rh2-enriched Korean ginseng (Ginseng Rh2+) using a forced exercise-induced chronic fatigue mouse model. Methods: ICR male mice were subjected to running wheel for 1 h, 5 days/week during 4 weeks, and running velocity was gradually increased. Each running session was followed by oral administration of distilled water, Ginseng Rh2+ (150 or 300 mg/kg), or N-acetyl-L-cysteine (NAC, 100 mg/kg) 1 h later. The exercise tolerance and forced swimming test were performed to evaluate the fatigue condition. Results: Chronic forced exercise reduced the physical activity, as evidenced by the behavioral tests, which were notably ameliorated by Ginseng Rh2+ treatment. Ginseng Rh2+ treatment also attenuated the alterations of energy metabolism and oxidative stress in skeletal muscle tissues and/or sera, including malondialdehyde (MDA), lactate concentration and its related factors (lactate dehydrogenase, blood urea nitrogen, and glucose levels). Conclusion: These findings strongly suggest that Ginseng Rh2+ exerts a potent anti-fatigue effect through modulation of energy metabolism and oxidative response.

The Beneficial Effect of Melatonin for Toluene Hepatotoxicity in Rats

  • Bae, Si-Woo;Yoon, In-Sook
    • Biomedical Science Letters
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    • v.7 no.3
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    • pp.99-102
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    • 2001
  • Toluene is mainly metabolized in liver by oxidative pathway. Oxigen free radicals occur through the process of toluene metabolism Therefore it causes tissue and cell min by the oxygen free radicals from the metabolism of toluene. Melatonin acts as a highly efficient free radical scavenger that protects cells from damage by oxygen free radicals. To test this hypothesis, toluene hepatotoxicity was induced by an abdominal injection of toluene. To see if the melatonin protects the rat's liver, melatonin was administrated orally, at the time of each toluene injection. Aspartate aminotransferase(AST), alanin aminotransferase(ALT), latic dehydrogenase(LDH) and alkaline phosphatase(ALP) levels in serum were measured to estimate hepatic function. Malondialdehyde(MDA), which gives an indirect index of oxidative injury was also measured. Hippuric acid is the last metabolic Production of toluene was measured by HPLC. There were significantly higher in AST, ALT, LDH, MDA and hippuric acid in toluene group, but there were no significant difference in melatonin group except ALT and hippuric acid. There was significantly lower in ALP level in toluene group, but there was no significant difference melatonin group, suggesting a significant hepatotoxicity due to oxygen free radicals through the process of toluene metabolism Melatonin treatment significantly protected hepatic function and free radical-mediated injury in the liver against toluene-induced changes. Accordingly, this study shows that melatonin is helpful in protecting liver injury by acute toluene intoxication.

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Pyruvate Protects Giardia Trophozoites from Cysteine-Ascorbate Deprived Medium Induced Cytotoxicity

  • Raj, Dibyendu;Chowdhury, Punam;Sarkar, Rituparna;Saito-Nakano, Yumiko;Okamoto, Keinosuke;Dutta, Shanta;Nozaki, Tomoyoshi;Ganguly, Sandipan
    • Parasites, Hosts and Diseases
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    • v.56 no.1
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    • pp.1-9
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    • 2018
  • Giardia lamblia, an anaerobic, amitochondriate protozoan parasite causes parasitic infection giardiasis in children and young adults. It produces pyruvate, a major metabolic product for its fermentative metabolism. The current study was undertaken to explore the effects of pyruvate as a physiological antioxidant during oxidative stress in Giardia by cysteine-ascorbate deprivation and further investigation upon the hypothesis that oxidative stress due to metabolism was the reason behind the cytotoxicity. We have estimated intracellular reactive oxygen species generation due to cysteine-ascorbate deprivation in Giardia. In the present study, we have examined the effects of extracellular addition of pyruvate, during oxidative stress generated from cysteine-ascorbate deprivation in culture media on DNA damage in Giardia. The intracellular pyruvate concentrations at several time points were measured in the trophozoites during stress. Trophozoites viability under cysteine-ascorbate deprived (CAD) medium in presence and absence of extracellular pyruvate has also been measured. The exogenous addition of a physiologically relevant concentration of pyruvate to trophozoites suspension was shown to attenuate the rate of ROS generation. We have demonstrated that Giardia protects itself from destructive consequences of ROS by maintaining the intracellular pyruvate concentration. Pyruvate recovers Giardia trophozoites from oxidative stress by decreasing the number of DNA breaks that might favor DNA repair.

Metabolism of Dietary Carotenoids and Effects to Improve the Body Color of Oily Bittering, Acheilognathus koreensis (칼납자루이 사료 Carotenoids 대사와 체색개선에 미치는 영향)

  • 백승한;김현영;김수영;정계임;권문정;김종현;하봉석
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.28 no.5
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    • pp.1099-1106
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    • 1999
  • Effects of dietary carotenoids were investigated on metabolism of the carotenoids, and body pigmen tation in oily bittering, Acheilognathus koreensis. Two weeks later after depletion,oily bitterings were fed the diets supplemented with either lutein, cynthiaxanthin and astaxathin for 4 weeks. Carotenoids distributed to and metabolized in integument were analyed. The carotenoid isolated from the integument of wild oily bittering, composed of 47.2% zeaxanthin, 11.4% lutein epoxide, 11.0% diatoxanthin, 9.7% lutein and 8.3% zeaxanthin epoxide. Meanwhile, two weeks later after depletion, the carotenoid composed of 29.9% crytoxanthin, 19.3% zeaxanthin, 13.2% lutein epoxide, 12.0% diatoxanthin and 8.8% zeaxanthin epoxide. These indicated that zeaxanthin, diatoxanthin, lutein epoxide and zeaxanthin epoxide were actively metabolized in oily bittering, compared to that of other fresh water fish. Total carotenoid content in the integument of wild oily bittering and oily bittering depleted for two weeks was found to be 1.72mg% and 2.08mg%, respectively. Two weeks later after treatment of experimental diet, total carotenoids content was increased to 2.23mg% in lutein, 2.36mg% in cynthiaxanthin and 2.49mg% in astaxanthin supplemented group, which were relatively higher than 2.10mg% in control group. Meanwhile, 4 weeks later, total ca rotenoids content was decreased to 1.76mg% in control, 1.95mg% in lutein, 1.74mg% in cynthiaxanthin and 1.72mg% in astaxanthin supplemented groups. These result indicate that dietary carotenoids were rapidly accumulated and then metabolized to certain metabolites shortly after feeding. Body pigmentation effects of the carotenoids due to accumulation of carotenoids in the integument of oily bittering was the most effectively shown in the astaxanthin supplemented group, followed by cynthiaxanthin and lutein supplemented groups. In the integument of oily bittering, dietary carotenoids were presumably biotrans formed via either oxidative or reductive pathways as presumed the variation of total carotenoid content and carotenoid composition in all experimental groups. The lutein was oxidized either to astaxanthin via doradexanthin and doradexanthin, or to zeaxanthin epoxide via zeaxanthin by oxidative pathway. Cynthiaxanthin was converted either to diatoxanthin and zeaxanthin by reductive pathway and then to zeaxanthin epoxide by oxidative pathway, or it was converted to astaxanthin via diatoxanthin, zeaxan thin and doradexanthin by oxidative pathway. Astaxanthin was converted to doradexanthin and zeaxanthin by reductive pathway and then to zeaxanthin epoxide by oxidative pathway. These results suggest that, oxidative pathway of carotenoids was major metabolic pathway along with reductive path way in fresh water fish.

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Energy Metabolism in Human Pluripotent Stem and Differentiated Cells Compared Using a Seahorse XF96 Extracellular Flux Analyzer

  • Hyun Kyu Kim;Yena Song;Minji Kye;Byeongho Yu;Sang Beom Park;Ji Hyeon Kim;Sung-Hwan Moon;Hyungkyu Choi;Jong-Seok Moon;Jae Sang Oh;Man Ryul Lee
    • International Journal of Stem Cells
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    • v.17 no.2
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    • pp.194-203
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    • 2024
  • Evaluating cell metabolism is crucial during pluripotent stem cell (PSC) differentiation and somatic cell reprogramming as it affects cell fate. As cultured stem cells are heterogeneous, a comparative analysis of relative metabolism using existing metabolic analysis methods is difficult, resulting in inaccuracies. In this study, we measured human PSC basal metabolic levels using a Seahorse analyzer. We used fibroblasts, human induced PSCs, and human embryonic stem cells to monitor changes in basal metabolic levels according to cell number and determine the number of cells suitable for analysis. We evaluated normalization methods using glucose and selected the most suitable for the metabolic analysis of heterogeneous PSCs during the reprogramming stage. The response of fibroblasts to glucose increased with starvation time, with oxygen consumption rate and extracellular acidification rate responding most effectively to glucose 4 hours after starvation and declining after 5 hours of starvation. Fibroblasts and PSCs achieved appropriate responses to glucose without damaging their metabolism 2~4 and 2~3 hours after starvation, respectively. We developed a novel method for comparing basal metabolic rates of fibroblasts and PSCs, focusing on quantitative analysis of glycolysis and oxidative phosphorylation using glucose without enzyme inhibitors. This protocol enables efficient comparison of energy metabolism among cell types, including undifferentiated PSCs, differentiated cells, and cells undergoing cellular reprogramming, and addresses critical issues, such as differences in basal metabolic levels and sensitivity to normalization, providing valuable insights into cellular energetics.

Effects of Oxidative Stress on Growth Performance, Nutrient Digestibilities and Activities of Antioxidative Enzymes of Weanling Pigs

  • Yuan, Shi-bin;Chen, Dai-wen;Zhang, Ke-ying;Yu, Bing
    • Asian-Australasian Journal of Animal Sciences
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    • v.20 no.10
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    • pp.1600-1605
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    • 2007
  • This study was undertaken to investigate the effects of oxidative stress on growth performance, nutrient digestibilities and activities of antioxidant enzymes of weanling pigs. In the experiment, 24 male $Landrance{\times}Yorkshire $weanling pigs were allotted to three groups of 8 animals each. Pigs were fed individually. According to a single factorial arrangement, pigs received diets with 5% of either fresh (group 1 and group 3) or oxidized fish oil (peroxide value was 786.50 meq $O_2/kg$ before inclusion in the diet, group 2). At the beginning of the experiment, pigs in group 3 received an intraperitoneal injection of diquat at 12 mg/kg of body weight. The trial lasted for 26 d. A metabolism test was carried out during the last 4 days of the second week. The results showed that feeding diets containing oxidized fish oil or injection with diquat depressed the growth performance and nutrient digestibilities of weanling pigs, decreased activities of antioxidant enzymes and increased concentration of malondialdehyde in plasma and liver. Intraperitoneal injection of diquat would induce more serious oxidative stress than oral intake of oxidized fish oil in the diet. In conclusion, administration of oxidized fish oil or diquat could induce oxidative stress in weanling pigs, and oxidative stress could depress growth performance and impact anti-oxidative ability of young pigs.