• Title/Summary/Keyword: ATP consumption rate

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Estimation of Cardiac Pumping Performance according to the Ventricular Electrical Activation Time Distribution by Using Physiome Model (피지옴 모델을 이용한 심실의 전기활성시간 분포에 따른 심박출 성능평가)

  • Kim, Hyeong-Gyun;Lim, Ki Moo
    • Journal of Biomedical Engineering Research
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    • v.36 no.5
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    • pp.198-203
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    • 2015
  • The purpose of the study is to examine the effects of pacemaker location on cardiac pumping efficacy theoretically. We used a three-dimensional finite element cardiac electromechanical model of canine ventricles with models of the circulatory system. Electrical activation time for normal sinus rhythm and artificial pacing in apex, left ventricular free wall, and right ventricular free wall were obtained from electrophysiological model. We applied the electrical activation time maps to the mechanical contraction model and obtained cardiac mechanical responses such as myocardial contractile ATP consumption, stroke work, stroke volume, ejection fraction, and etc. Among three artificial pacing methods, left ventricle pacing showed best performance in ventricular pumping efficacy.

Prophylactic role of Korean Red Ginseng in astrocytic mitochondrial biogenesis through HIF-1α

  • Park, Jinhong;Lee, Minjae;Kim, Minsu;Moon, Sunhong;Kim, Seunghee;Kim, Sueun;Koh, Seong-Ho;Kim, Young-Myeong;Choi, Yoon Kyung
    • Journal of Ginseng Research
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    • v.46 no.3
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    • pp.408-417
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    • 2022
  • Background: Korean Red Ginseng extract (KRGE) has been used as a health supplement and herbal medicine. Astrocytes are one of the key cells in the central nervous system (CNS) and have bioenergetic potential as they stimulate mitochondrial biogenesis. They play a critical role in connecting the brain vasculature and nerves in the CNS. Methods: Brain samples from KRGE-administered mice were tested using immunohistochemistry. Treatment of human brain astrocytes with KRGE was subjected to assays such as proliferation, cytotoxicity, Mitotracker, ATP production, and O2 consumption rate as well as western blotting to demonstrate the expression of proteins related to mitochondria functions. The expression of hypoxia-inducible factor-1α (HIF-1α) was diminished utilizing siRNA transfection. Results: Brain samples from KRGE-administered mice harbored an increased number of GFAP-expressing astrocytes. KRGE triggered the proliferation of astrocytes in vitro. Enhanced mitochondrial biogenesis induced by KRGE was detected using Mitotracker staining, ATP production, and O2 consumption rate assays. The expression of proteins related to mitochondrial electron transport was increased in KRGE-treated astrocytes. These effects were blocked by HIF-1α knockdown. The factors secreted from KRGE-treated astrocytes were determined, revealing the expression of various cytokines and growth factors, especially those related to angiogenesis and neurogenesis. KRGE-treated astrocyte conditioned media enhanced the differentiation of adult neural stem cells into mature neurons, increasing the migration of endothelial cells, and these effects were reduced in the background of HIF-1α knockdown. Conclusion: Our findings suggest that KRGE exhibits prophylactic potential by stimulating astrocyte mitochondrial biogenesis through HIF-1α, resulting in improved neurovascular function.

microRNA-200a-3p enhances mitochondrial elongation by targeting mitochondrial fission factor

  • Lee, Heejin;Tak, Hyosun;Park, So Jung;Jo, Yoon Kyung;Cho, Dong Hyung;Lee, Eun Kyung
    • BMB Reports
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    • v.50 no.4
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    • pp.214-219
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    • 2017
  • Mitochondria play pivotal roles in the ATP production, apoptosis and generation of reactive oxygen species. Although dynamic regulation of mitochondria morphology is a critical step to maintain cellular homeostasis, the regulatory mechanisms are not yet fully elucidated. In this study, we identified miR-200a-3p as a novel regulator of mitochondrial dynamics by targeting mitochondrial fission factor (MFF). We demonstrated that the ectopic expression of miR-200a-3p enhanced mitochondrial elongation, mitochondrial ATP synthesis, mitochondrial membrane potential and oxygen consumption rate. These results indicate that miR-200a-3p positively regulates mitochondrial elongation by downregulating MFF expression.

Effects of Taurine Supplementation on Mitochondrial Function in Chronic Ethanol Administered Rats

  • Shim Kwan-Seop;Park Garng-Hee;Kim Sook-Bae
    • Journal of Community Nutrition
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    • v.7 no.3
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    • pp.163-168
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    • 2005
  • The present investigation was undertaken in vivo to determine whether the functional alterations of hepatic mitochondria induced by ethanol might be prevented by taurine. We examined the effects of supplementation of taurine on hepatic mitochondrial oxidative phosphorylation in the chronic ethanol-administered rats. Isolated hepatic mitochondria from three groups of rats were functionally tested by an analysis of $\beta-hydroxbutyrate-supported$ respiration and the coupling of this process to ATP synthesis in the presence of ADP. The three groups were control group(CO), ethanol(60g/L) administered group (AL), and ethanol (60g/L) + taurine (5g/L) supplemented group (AT). Ethanol and/or taurine were given in drinking water for 10 weeks. The mitochondria from AL group had lower state 4 respiratory rate, respiratory control (RC) ratio and ADP : O(P/O) ratio than those from CO and AT group. It showed that the ethanol administered rats were less coupled and thus less efficient with respect to mitochondrial ATP synthesis than both control rats and ethanol + taurine supplemented rats. It suggests that taurine supplementation might improve the impaired oxidative phosphorylation efficiency in mitochondrial dysfunction that is recognized as a cause of liver diseases in chronic ethanol consumption.

Optimal Cutoff Points of Rate Pressure Product in Each Stage of Treadmill Exercise Test According to the Degree of Metabolic Syndrome in Korean Adults (한국성인의 대사증후군 예방을 위한 운동부하 검사시 각 단계별 심근부담률의 적정 임계점)

  • Shin, Kyung-A
    • Korean Journal of Clinical Laboratory Science
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    • v.50 no.2
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    • pp.136-143
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    • 2018
  • The rate pressure product (RPP) is expressed as a product of the heart rate and systolic blood pressure as an index indirectly measuring the myocardial oxygen consumption, and it indicates the burden on the myocardium. The aim of this study was to determine the optimal level of RPP for preventing metabolic syndrome in a treadmill exercise test in Korean adults. Metabolic syndrome was the diagnosis of the third executive summary report on the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria. According to the criteria, the metabolic syndrome diagnosis group (MetS, N=25), pre-metabolic syndrome group (Pre-MetS, N=106), and non-risk factor group (Non-MetS, N=65) were classified. The exercise stress test was performed based on the Bruce protocol. The RPP was calculated as (heart rate${\times}$systolic blood pressure)${\div}1,000$. The results showed that the maximum systolic blood pressure was high despite the low daily dose reached in the diagnostic group of metabolic syndrome. The optimal threshold of the RPP at the time of the exercise treadmill test for a metabolic syndrome prediction was $12.56mmHg{\times}beats/min{\times}10^{-3}$ in the first stage of the exercise stress test. The second stage of the exercise test was $16.94mmHg{\times}beats/min{\times}10^{-3}$, and at the third stage of the exercise test was $21.11mmHg{\times}beats/min{\times}10^{-3}$.

Effect of Genotype on Whole-body and Intestinal Metabolic Response to Monensin in Mice

  • Fan, Y.K.;Croom, W.J.;Daniel, Linda;McBride, B.W.;Koci, M.;Havenstein, G.B.;Eisen, E.J.
    • Asian-Australasian Journal of Animal Sciences
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    • v.19 no.4
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    • pp.554-562
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    • 2006
  • Two lines of mice, M16 selected for rapid growth and a randomly selected control ICR as well as their reciprocal crosses were used to study the effects of genotype on whole-body energetics and intestinal responses to monensin. Six mice, eight weeks of age, from each line or reciprocal cross were assigned to one of two treatments, 1) drinking water containing 20 mmol/L monensin dissolved in 0.5% V/V ethanol, and 2) drinking water containing 0.5% V/V ethanol (control) for two weeks. After 11 days (age of 9 weeks and 4 days), whole-body $O_2$ consumption was measured. At the end of two weeks, jejunal $O_2$ consumption, intestinal tissue composition and histomorphometrics as well as the rate and efficiency of glucose absorption were estimated. In comparison with the control, monensin administration in drinking water resulted in less daily water intake (13.4 vs. 15.5 ml/mouse, p<0.01), less protein to DNA ratio of jejunal mucosa (5.41 vs. 6.01 mg/mg, p<0.05), lower villus width (88 vs. $100{\mu}m$, p<0.05), and less jejunal tissue $O_2$ consumption enhancement by alcohol (7.2 vs. 10.5%, p<0.01) in mice. Other than those changes, monensin had little (p>0.05) effect on variables measured in either line of mice or their reciprocal cross. In contrast, the M16 line, selected for rapid growth, as compared to the ICR controls or the reciprocal crosses, had less initial (pre-monensin treatment) whole-body $O_2$ consumption per gram of body weight (1.68 vs. $2.11-2.34{\mu}mol/min{\cdot}g$ BW, p<0.01) as compared to the ICR and reciprocal crosses. In addition, the M16 mice exhibited greater growth (412 vs. 137-210 mg/d, p<0.05), better feed efficiency (41.7 vs. 19.9-29.3 mg gain/g feed, p<0.05), shorter small intestines adjusted for fasted body weight (1.00 vs. 1.22-1.44 cm/g FBW, p<0.05), wider villi (109 vs. $87-93{\mu}m$, p<0.05), more mature height of enterocytes (28.8 vs. $24.4-25.1{\mu}m$, p<0.05) and a lower rate (91 vs. $133-145{\eta}mol\;glucose/min{\cdot}g$ jejunum, p<0.05) and less energetic efficiency (95 vs. $59-72{\eta}mol$ ATP expended/${\eta}mol$ glucose uptake, p<0.05) of glucose absorption compared to the ICR line and the reciprocal cross. Monensin had little (p>0.05) effect on whole-body $O_2$ consumption and jejunal function, whilst selection for rapid growth resulted in an apparent down-regulation of intestinal function. These data suggest that genetic selection for increased growth does not result in concomitant changes in intestinal function. This asynchrony in the selection for production traits and intestinal function may hinder full phenotypic expression of genotypic growth potential.

Energy metabolism and whole-exome sequencing-based analysis of Sasang constitution: a pilot study

  • Kim, Hyoung Kyu;Lee, Heetak;So, Ji Ho;Jeong, Seung Hun;Seo, Dae Yun;Kim, Jong-Yeol;Kim, Sanguk;Han, Jin
    • Integrative Medicine Research
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    • v.6 no.2
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    • pp.165-178
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    • 2017
  • Background: Traditional Korean Sasang constitutional (SC) medicine categorizes individuals into four constitutional types [Tae-eum (TE), So-eum (SE), Tae-yang (TY), or So-yang (SY)] based on biological and physiological characteristics. As these characteristics are closely related to the bioenergetics of the human body, we assessed the correlation between SC type and energy metabolism features. Methods: Forty healthy, young ($22.3{\pm}1.4$ years) males volunteered to participate in this study. Participants answered an SC questionnaire, and their face shape, voice tone, and body shape were assessed using an SC analysis tool. Thirty-one participants (10 TE, 10 SE, 3 TY, and 8 SY) were selected for further analysis. Collected blood samples were subjected to blood composition analysis, mitochondrial function analysis, and whole-exome sequencing. Results: The SY type showed significantly lower total cholesterol and high-density lipoprotein cholesterol levels than the SE type. Cellular and mitochondrial Adenosine triphosphate (ATP) levels were similar across types. All types showed similar basal mitochondrial oxygen consumption rates, whereas the TE type showed a significantly lower ATP-linked oxygen consumption rate than the other types. Whole-exome sequencing identified several genes variants that were exclusively detected in particular SC types, including 19 for SE, seven for SY, 11 for TE, and six for TY. Conclusion: SC type-specific differences in mitochondrial function and gene mutations were detected in a small group of healthy, young Korean males. These results are expected to greatly improve the accurate screening and utilization of SC medicine.

Major ginsenosides from Panax ginseng promote aerobic cellular respiration and SIRT1-mediated mitochondrial biosynthesis in cardiomyocytes and neurons

  • Huang, Qingxia;Lou, Tingting;Lu, Jing;Wang, Manying;Chen, Xuenan;Xue, Linyuan;Tang, Xiaolei;Qi, Wenxiu;Zhang, Zepeng;Su, Hang;Jin, Wenqi;Jing, Chenxu;Zhao, Daqing;Sun, Liwei;Li, Xiangyan
    • Journal of Ginseng Research
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    • v.46 no.6
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    • pp.759-770
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    • 2022
  • Background: Aerobic cellular respiration provides chemical energy, adenosine triphosphate (ATP), to maintain multiple cellular functions. Sirtuin 1 (SIRT1) can deacetylate peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) to promote mitochondrial biosynthesis. Targeting energy metabolism is a potential strategy for the prevention and treatment of various diseases, such as cardiac and neurological disorders. Ginsenosides, one of the major bioactive constituents of Panax ginseng, have been extensively used due to their diverse beneficial effects on healthy subjects and patients with different diseases. However, the underlying molecular mechanisms of total ginsenosides (GS) on energy metabolism remain unclear. Methods: In this study, oxygen consumption rate, ATP production, mitochondrial biosynthesis, glucose metabolism, and SIRT1-PGC-1α pathways in untreated and GS-treated different cells, fly, and mouse models were investigated. Results: GS pretreatment enhanced mitochondrial respiration capacity and ATP production in aerobic respiration-dominated cardiomyocytes and neurons, and promoted tricarboxylic acid metabolism in cardiomyocytes. Moreover, GS clearly enhanced NAD+-dependent SIRT1 activation to increase mitochondrial biosynthesis in cardiomyocytes and neurons, which was completely abrogated by nicotinamide. Importantly, ginsenoside monomers, such as Rg1, Re, Rf, Rb1, Rc, Rh1, Rb2, and Rb3, were found to activate SIRT1 and promote energy metabolism. Conclusion: This study may provide new insights into the extensive application of ginseng for cardiac and neurological protection in healthy subjects and patients.

Clinical Evaluation of Bromovincamine for Cerebral Stroke (뇌졸중 환자에서의 Brovincamine의 임상효과)

  • 김준석;서홍석;오동주;임도선
    • YAKHAK HOEJI
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    • v.37 no.1
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    • pp.84-88
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    • 1993
  • Brovincamine is a selective cerebral vasodilator that was apparently produced via a slow calcium blockade. Brovincamine has been shown to increase ATP production and glucose and oxygen consumption in brain, improving energy metabolism. Also brovincamine inhibited platelet aggregation induced by ADP and collagen in vivo and in vitro via an increase of cAMP concentration, promoting therapeutic effects on cerebral circulatory disorders. So we investigated and represented the clinical effects and safety of brovincamine in patients with cerebral stroke. Thirty patients of cerebral stroke that was older than 2 months, who were 22 cases of cerebral infarction, 6 of cerebral embolism that originated from carebral infarction, 6 of cerebral embolism that originated from cardiac diseases, and 2 of cerebral embolism that originated from cardiac diseases, and 2 of cerebral hemorrhage, were administered of 20 mg of oral brovincamine three times daily for 8 weeks. Improvement rates of each symptom after 8 week administration were 30.8% for subjective symptoms, 76% for psychiatric symptoms and 65.6% for neurologic symptoms. In final global improvement rates, much improvement was 10%, improvement was 23.3% slight improvement is 36.7%, and no change was 30%. So global improvement rate including slight improvement was 70%. As for side effects, there were 3 cases of mild gastrointestinal symptoms, but there were no other subjective side effects and significant fluctuation in laboratory examination. Conclusively throughout the present study, brovincamine is judged to be well tolerated and effective in patients with cerebral stroke.

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Ginsenosides attenuate bioenergetics and morphology of mitochondria in cultured PC12 cells under the insult of amyloid beta-peptide

  • Kwan, Kenneth Kin Leung;Yun, Huang;Dong, Tina Ting Xia;Tsim, Karl Wah Keung
    • Journal of Ginseng Research
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    • v.45 no.4
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    • pp.473-481
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    • 2021
  • Background: Mitochondrial dysfunction is one of the significant reasons for Alzheimer's disease (AD). Ginsenosides, natural molecules extracted from Panax ginseng, have been demonstrated to exert essential neuroprotective functions, which can ascribe to its anti-oxidative effect, enhancing central metabolism and improving mitochondrial function. However, a comprehensive analysis of cellular mitochondrial bioenergetics after ginsenoside treatment under Aβ-oxidative stress is missing. Methods: The antioxidant activities of ginsenoside Rb1, Rd, Re, Rg1 were compared by measuring the cell survival and reactive oxygen species (ROS) formation. Next, the protective effects of ginsenosides of mitochondrial bioenergetics were examined by measuring oxygen consumption rate (OCR) in PC12 cells under Aβ-oxidative stress with an extracellular flux analyzer. Meanwhile, mitochondrial membrane potential (MMP) and mitochondrial dynamics were evaluated by confocal laser scanning microscopy. Results: Ginsenoside Rg1 possessed the strongest anti-oxidative property, and which therefore provided the best protective function to PC12 cells under the Aβ oxidative stress by increasing ATP production to 3 folds, spare capacity to 2 folds, maximal respiration to 2 folds and non-mitochondrial respiration to 1.5 folds, as compared to Aβ cell model. Furthermore, ginsenoside Rg1 enhanced MMP and mitochondrial interconnectivity, and simultaneously reduced mitochondrial circularity. Conclusion: In the present study, these results demonstrated that ginsenoside Rg1 could be the best natural compound, as compared with other ginsenosides, by modulating the OCR of cultured PC12 cells during oxidative phosphorylation, in regulating MMP and in improving mitochondria dynamics under Aβ-induced oxidative stress.