• Journal of Institute of Control, Robotics and Systems
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• v.11 no.10
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• pp.843-850
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• 2005

FBA(flux balance analysis) with Boolean rules for representing regulatory events has correctly predicted cellular behaviors, such as optimal flux distribution, maximal growth rate, metabolic by-product, and substrate concentration changes, with various environmental conditions. However, until now, since FBA has not taken into account a hierarchical regulatory network, it has limited the representation of the whole transcriptional regulation mechanism and interactions between specific regulatory proteins and genes. In this paper, in order to solve these problems, we describe the construction of hierarchical regulatory network with defined symbols and the introduction of a weight for representing interactions between symbols. Finally, the whole cellular behaviors with time were simulated through the linkage of a hierarchical regulatory network module and dynamic simulation module including FBA. The central metabolic network of E. coli was chosen as the basic model to identify our suggested modeling method.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.1
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• pp.41-46
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• 2002

Effect of cadmium (Cd) intoxication on renal acid-base regulation was studied in adult male Sprague-Dawley rats. Cd intoxication was induced by subcutaneous injections of $CdCl_2$ at a dose of 2 mg Cd/kg/day for $3{\sim}4$ weeks. In Cd-intoxicated animals, arterial pH, $PCO_2$ and plasma bicarbonate concentration decreased, showing a metabolic acidosis. Urine pH and urinary bicarbonate excretion increased and titratable acid excretion decreased with no change in ammonium excretion. In renal cortical brush-border membrane vesicles derived from Cd-exposed animals, the $Na^+/H^+$ antiporter activity was significantly attenuated. These results indicate that chronic exposures to Cd impair the proximal tubular mechanism for $H^+$ secretion (i.e., $Na^+/H^+$ antiport), leading to a metabolic acidosis.

• Biomolecules & Therapeutics
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• v.23 no.2
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• pp.99-109
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• 2015

Drug development groups are close to discovering another pot of gold-a therapeutic target-similar to the success of imatinib (Gleevec) in the field of cancer biology. Modern molecular biology has improved cancer therapy through the identification of more pharmaceutically viable targets, and yet major problems and risks associated with late-phase cancer therapy remain. Presently, a growing number of reports have initiated a discussion about the benefits of metabolic regulation in cancers. The Warburg effect, a great discovery approximately 70 years ago, addresses the "universality" of cancer characteristics. For instance, most cancer cells prefer aerobic glycolysis instead of mitochondrial respiration. Recently, cancer metabolism has been explained not only by metabolites but also through modern molecular and chemical biological techniques. Scientists are seeking context-dependent universality among cancer types according to metabolic and enzymatic pathway signatures. This review presents current cancer metabolism studies and discusses future directions in cancer therapy targeting bio-energetics, bio-anabolism, and autophagy, emphasizing the important contribution of cancer metabolism in cancer therapy.

• 한국유가공학회:학술대회논문집
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• 2002.04a
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• pp.45-55
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• 2002

Recent developments in the application of molecular biology to food grade lactic acid bacteria (LAB) have shown that it could be feasible to engineer metabolic pathways to either enhance specific metabolic fluxes or to divert metabolites for the production of different or new end products. This engineering requires detailed knowledge of enzymes involved in metabolism and regulation within the targeted organism but little works have been done in this area. During biochemical and molecular characterisation of lactic bacterial enzymes, some of probiotic Lactobacillus and Bifidobacterium species were found to be very useful for food, nutraceutical and pharmaceutical industries. The enzymes are usually intracellular and the yields are very low to be useful for industrial applications. Among many enzymes and proteins of lactic bacteria studied, some of our gene cloning achievements have contributed to overproduction of lactic bacterial enzymes such as peptidases, esterases, lactases, bile salt hydrolases and linoleate isomerases for foods and nutraceuticals.

• Clinical and Experimental Pediatrics
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• v.55 no.9
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• pp.316-321
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• 2012

The ketogenic diet has been widely used and proved to be effective for intractable epilepsy. Although the mechanisms underlying its antiepileptic effects remain to be proven, there are increasing experimental evidences for its neuroprotective effects along with many researches about expanding use of the diet in other neurologic disorders. The first success was reported in glucose transporter type 1 deficiency syndrome, in which the diet served as an alternative metabolic source. Many neurologic disorders share some of the common pathologic mechanisms such as mitochondrial dysfunction, altered neurotransmitter function and synaptic transmission, or abnormal regulation of reactive oxygen species, and the role of the ketogenic diet has been postulated in these mechanisms. In this article, we introduce an overview about the expanding use and emerging trials of the ketogenic diet in various neurologic disorders excluding intractable epilepsy and provide explanations of the mechanisms in that usage.

• Sleep Medicine and Psychophysiology
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• v.19 no.1
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• pp.5-10
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• 2012

The release of hormones and the metabolism of human body are controlled by the circadian rhythm related to sleep-wake cycle. Growth hormone, prolactin, thyroid stimulating hormone, cortisol, glucose, and insulin-secretion rates fluctuate according to the sleep-wake cycle. In addition, sleep is related to the appetite regulation and carbohydrate and other energy metabolism. Hypocretin (orexin), an excitatory neuropeptide, regulates waking and diet intake, and the poor sleep increases diet intake. The short sleep duration increases one's body mass index and impairs the function of the endocrine and metabolism, causing increases in the risk of glucose intolerance and diabetes. The poor sleep quality and sleep disorders have similar impact on the metabolic function. In short, the sleep loss and the poor quality of sleep have a detrimental effect on the endocrine and energy metabolism. The improvement of sleep quality by the future research and appropriate clinical treatment would contribute to the decrease of the metabolic diseases such as diabetes.

• BMB Reports
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• v.50 no.7
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• pp.367-372
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• 2017

Monoacylglycerol acyltransferase 1 (MGAT) is a microsomal enzyme that catalyzes the synthesis of diacylglycerol (DAG) and triacylglycerol (TAG). However, the subcellular localization and catalytic function domain of this enzyme is poorly understood. In this report, we identified that murine MGAT1 localizes to the endoplasmic reticulum (ER) under normal conditions, whereas MGAT1 co-localize to the lipid droplets (LD) under conditions of enriching fatty acids, contributing to TAG synthesis and LD expansion. For the enzyme activity, both the N-terminal transmembrane domain and catalytic HPHG motif are required. We also show that the transmembrane domain of MGAT1 consists of two hydrophobic regions in the N-terminus, and the consensus sequence FLXLXXXn, a putative neutral lipid-binding domain, exists in the first transmembrane domain. Finally, MGAT1 interacts with DGAT2, which serves to synergistically increase the TAG biosynthesis and LD expansion, leading to enhancement of lipid accumulation in the liver and fat.

• Molecules and Cells
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• v.45 no.11
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• pp.771-780
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• 2022

The field of extracellular vesicles (EVs) has expanded tremendously over the last decade. The role of cell-to-cell communication in neighboring or distant cells has been increasingly ascribed to EVs generated by various cells. Initially, EVs were thought to a means of cellular debris or disposal system of unwanted cellular materials that provided an alternative to autolysis in lysosomes. Intercellular exchange of information has been considered to be achieved by well-known systems such as hormones, cytokines, and nervous networks. However, most research in this field has searched for and found evidence to support paracrine or endocrine roles of EV, which inevitably leads to a new concept that EVs are synthesized to achieve their paracrine or endocrine purposes. Here, we attempted to verify the endocrine role of EV production and their contents, such as RNAs and bioactive proteins, from the regulation of biogenesis, secretion, and action mechanisms while discussing the current technical limitations. It will also be important to discuss how blood EV concentrations are regulated as if EVs are humoral endocrine machinery.

• BMB Reports
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• v.42 no.7
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• pp.421-426
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• 2009

Glucocorticoids regulate multiple physiological processes such as metabolic homeostasis and immune response. Mouse Pon2 (mPon2) acts as an antioxidant to reduce cellular oxidative stress in cells. In this present study, we investigated the transcriptional regulation of mPon2 by glucocorticoids. In the presence of glucocorticoid analogue dexamethasone, the expression of mPon2 mRNA in cells was increased, whereas the expression was inhibited by a transcription inhibitor actinomycin D. Glucocorticoid receptors bound to the putative glucocorticoid response elements located between -593 bp and -575 bp of the mPon2 promoter. Transcriptional activity was completely blocked when the putative element was mutated. Taken together, these results suggest that the expression of the mPon2 gene is directly regulated by glucocorticoid-glucocorticoid receptor complexes.

• Natural Product Sciences
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• v.10 no.5
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• pp.197-206
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• 2004

Cytochrome P4501A2 (CYP1A2) is responsible for the metabolic activation of a number of aromatic amines and amides to mutagenic and carcinogenic moieties. Considerable variations in the level of CYP1A2 expression in humans have been reported. Thus, the level of human CYP1A2 may determine an individuals susceptibility to these chemicals. Given its importance, the molecular mechanisms of CYP1A2 regulation have been studied by many groups. Direct interactions between transcription factors with the promoters of the gene represent one of the primary means by which the expression of CYP1A2 is controlled. In this review, several important cis elements, transcription factors and the effects of deacetylation/methylation of promoter regions that play an important role in the induction by PAHs as well as constitutive expression of human CYP1A2 are discussed.