• BMB Reports
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• 제30권2호
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• pp.138-143
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• 1997

In order to assess controversial' proposals concerning the fatty acid-induced uncoupling of mitochondrial oxidative phosphorylation, we investigated the interaction of stearic acid with key mitochondrial proteins and measured the effect of stearic acid on the respiration of cytochrome c oxidase vesicles. Electron paramagnetic resonance spectra of spin-labeled stearic acid clearly demonstrated that cytochrome c oxidase interacts strongly with stearic acid. However, the respiration of detergent-solubilized cytochrome c oxidase was not altered significantly by stearic acid. Surprisingly, adenine nucleotide carrier, which was assumed to bind and translocate fatty acid anions in the Skulachev model of uncoupling, did not bind stearic acid at all. The respiration rate of cytochrome c oxidase vesicles was increased by ~70% in the presence of $20{\mu}m$ stearic acid and this uncoupling was attributed to a simple protonophoric effect of stearic acid.

• BMB Reports
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• 제28권1호
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• pp.12-16
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• 1995

The branched-chain ${\alpha}$-keto acid dehydrogenase (BCKAD) complex is a rate limiting enzyme which catalyzes the oxidative decarboxylation of branched-chain ${\alpha}$-keto acids. Numerous studies have suggested that BCKAD is subject to covalent modification in vitro via phosphorylation and dephosphorylation, which are catalyzed by a specific kinase and phosphatase, respectively. The biggest difficulty in the assay of BCKAD activity is to arrest the interconversion between the active and inactive forms. BCKAD activity was determined from fresh rat heart and liver tissues using homogenizing and assay buffers containing inhibitors of phosphatase and kinase. The results suggest that a radiochemical assay using ${\alpha}$-keto[1-$^{14}C$]-isovalerate as a substrate for the enzyme can be applied as a reliable method to determine in vitro enzyme activity with arrested interconversion between the active and inactive forms of the BCKAD complex.

• BMB Reports
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• 제50권9호
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• pp.435-436
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• 2017

Primed human pluripotent stem cells (hPSCs) are highly dependent on glycolysis rather than oxidative phosphorylation, which is similar to the metabolic switch that occurs in cancer cells. However, the molecular mechanisms that underlie this metabolic reprogramming in hPSCs and its relevance to pluripotency remain unclear. Cha et al. (2017) recently revealed that downregulation of SIRT2 by miR-200c enhances acetylation of glycolytic enzymes and glycolysis, which in turn facilitates cellular reprogramming, suggesting that SIRT2 is a key enzyme linking the metabolic switch and pluripotency in hPSCs.

• Biomolecules & Therapeutics
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• 제22권4호
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• pp.308-313
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• 2014

Activator protein-1 (AP-1) is an inducible transcription factor that contributes to the generation of chronic inflammation in response to oxidative and electrophilic stress. Previous studies have demonstrated that the PI3K/Akt1 pathway plays an important role in the transcriptional regulation of AP-1 expression. Although the histone post-translational modifications (PTMs) are assumed to affect the AP-1 transcriptional regulation by the PI3K/Akt pathway, the detailed mechanisms are completely unknown. In the present study, we show that heterochromatin 1 gamma ($HP1{\gamma}$) plays a negative role in TPA-induced c-Jun and c-Fos expression. We show that TPA-induced Akt1 directly phosphorylates $HP1{\gamma}$, abrogates its suppressive function and increases the interaction between histone H3 and 14-3-$3{\varepsilon}$. Collectively, these our data illustrate that the activation of PI3K/Akt pathway may play a permissive role in the recruitment of histone readers or other coactivators on the chromatin, thereby affecting the degree of AP-1 transcription.

• BMB Reports
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• 제46권8호
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• pp.398-403
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• 2013

Inflammatory conditions mediated by activated microglia lead to chronic neuro-degenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases. This study was conducted to determine the effect of floridoside isolated from marine red algae Laurencia undulata on LPS (100 ng/ml) activated inflammatory responses in BV-2 microglia cells. The results show that floridoside has the ability to suppress pro-inflammatory responses in microglia by markedly inhibiting the production of nitric oxide (NO) and reactive oxygen species (ROS). Moreover, floridoside down-regulated the protein and gene expression levels of iNOS and COX-2 by significantly blocking the phosphorylation of p38 and ERK in BV-2 cells. Collectively, these results indicate that floridoside has the potential to be developed as an active agent for the treatment of neuro-inflammation.

• Biomolecules & Therapeutics
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• 제20권2호
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• pp.144-151
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• 2012

The molecular mechanisms by which a variety of naturally-occurring dietary compounds exert chemopreventive effects have been a subject of intense scientific investigations. Induction of phase II detoxification and anti-oxidant enzymes through activation of Nrf2/ARE-dependent gene is recognized as one of the major cellular defense mechanisms against oxidative or xenobiotic stresses and currently represents a critical chemopreventive mechanism of action. In the present review, the functional significance of Keap1/Nrf2 protein module in regulating ARE-dependent phase II detoxification and anti-oxidant gene expression is discussed. The biochemical mechanisms underlying the phosphorylation and expression of Keap1/Nrf2 proteins that are controlled by the intracellular signaling kinases and ubiquitin-mediated E3 ligase system as well as control of nucleocytoplasmic translocation of Nrf2 by its innate nuclear export signal (NES) are described.

• Journal of Pharmaceutical Investigation
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• 제6권3호
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• pp.26-42
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• 1976

The oral admistration of deer horn extract was proved to cause a considerable amelioration to the impairment of hepatic oxidative phosphorylation and to the decrease of ATP content in liver tissue induced by cholesterol ingestion. Deer horn extract was shown to accelerate considerably incorporation of $acetate-1-C^{14}$ into cholesterol in liver tissue and it tends to restore a decrease of GOT activity of liver tissue, caused by cholesterol administration. Histological examination showed that deer horn extract had a remakable preventive effect aginst fatty infiltration of organgs such as liver, heart, spleen, and adrenal gland of cholesterol given rabbits.

• BMB Reports
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• 제47권3호
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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.

• BMB Reports
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• 제53권1호
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• pp.3-9
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• 2020

The mitochondrial genome encodes 13 proteins that are components of the oxidative phosphorylation system (OXPHOS), suggesting that precise regulation of these genes is crucial for maintaining OXPHOS functions, including ATP production, calcium buffering, cell signaling, ROS production, and apoptosis. Furthermore, heteroplasmy or mis-regulation of gene expression in mitochondria frequently is associated with human mitochondrial diseases. Thus, various approaches have been developed to investigate the roles of genes encoded by the mitochondrial genome. In this review, we will discuss a wide range of techniques available for investigating the mitochondrial genome, mitochondrial transcription, and mitochondrial translation, which provide a useful guide to understanding mitochondrial gene expression.

• 식품과학과 산업
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• 제55권3호
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• pp.264-275
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• 2022

The regulation of macrophages is a major target for dietary immune modulation for their involvement in both innate and adoptive immune responses. Studies revealed that macrophages are unique in their plasticity to polarize into either inflammatory M1 subset or anti-inflammatory M2 cells. Recently, cellular energy metabolism including both glycolysis and oxidative phosphorylation is demonstrated to control macrophage dichotomy. In this review, the differential utilization of glucose, lipids, amino acids, and irons by M1 and M2 cells are discussed in detail. In addition, several dietary approaches for the alteration of inflammatory M1 cells to M2 phenotypes are reviewed for development of functional foods for immune regulation.