• Title/Summary/Keyword: metabolic disease

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The Critical Roles of Zinc: Beyond Impact on Myocardial Signaling

  • Lee, Sung Ryul;Noh, Su Jin;Pronto, Julius Ryan;Jeong, Yu Jeong;Kim, Hyoung Kyu;Song, In Sung;Xu, Zhelong;Kwon, Hyog Young;Kang, Se Chan;Sohn, Eun-Hwa;Ko, Kyung Soo;Rhee, Byoung Doo;Kim, Nari;Han, Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.19 no.5
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    • pp.389-399
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    • 2015
  • Zinc has been considered as a vital constituent of proteins, including enzymes. Mobile reactive zinc ($Zn^{2+}$) is the key form of zinc involved in signal transductions, which are mainly driven by its binding to proteins or the release of zinc from proteins, possibly via a redox switch. There has been growing evidence of zinc's critical role in cell signaling, due to its flexible coordination geometry and rapid shifts in protein conformation to perform biological reactions. The importance and complexity of $Zn^{2+}$ activity has been presumed to parallel the degree of calcium's participation in cellular processes. Whole body and cellular $Zn^{2+}$ levels are largely regulated by metallothioneins (MTs), $Zn^{2+}$ importers (ZIPs), and $Zn^{2+}$ transporters (ZnTs). Numerous proteins involved in signaling pathways, mitochondrial metabolism, and ion channels that play a pivotal role in controlling cardiac contractility are common targets of $Zn^{2+}$. However, these regulatory actions of $Zn^{2+}$ are not limited to the function of the heart, but also extend to numerous other organ systems, such as the central nervous system, immune system, cardiovascular tissue, and secretory glands, such as the pancreas, prostate, and mammary glands. In this review, the regulation of cellular $Zn^{2+}$ levels, $Zn^{2+}$-mediated signal transduction, impacts of $Zn^{2+}$ on ion channels and mitochondrial metabolism, and finally, the implications of $Zn^{2+}$ in health and disease development were outlined to help widen the current understanding of the versatile and complex roles of $Zn^{2+}$.

Diagnostic Method for Inborn Metabolic Disorders using differentiation between D- and R- Isomers on GC-MS (D체와 R체 이성질체 판별과 GC-MS를 이용한 유전성 대사이상질환의 진단법 개발)

  • Yoon, Hye-Ran
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.15 no.2
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    • pp.65-71
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    • 2015
  • Since the secretion of specific chiral isomers in urine (or plasma) is very crucial to diagnose some inborn metabolic disorders, clinical application of dual column achiral differential method has been performed for the absolute configuration of chiral compounds. Extracted from the acidified urine with diethyl ether, carboxylic functional group of organic acid (stereoisomers of the volatile) was derivatized with (-)-menthylation or (S)-(+)-3-methyl-2-butylation and followed by O-trifluoroacylation. Each of the enantiomers was accurately separated from the library matched double column (achiral) with a retention index (I). In various inborn metabolic disease urines, absolute chirality was identified correctly in the urine (10 patients) with inborn metabolic disease (including secretion of D, L- lactic acid, D, L-3-hydroxybutyric acid, and D, L-2-hydroxyglutaric acid). In this study, we identified and isolated the volatile diastereomer as a useful diagnostic marker, this successful application to urine specimens may be useful for diagnostic classification of inherited metabolic disorders.

Differential Activation of Ras/Raf/MAPK Pathway between Heart and Cerebral Artery in Isoproterenol-induced Cardiac Hypertrophy

  • Kim, Hyun-Ju;Kim, Na-Ri;Joo, Hyun;Youm, Jae-Boum;Park, Won-Sun;Warda, Mohamed;Kang, Sung-Hyun;Thu, Vu-Thi;Khoa, Tran-Minh;Han, Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.9 no.5
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    • pp.299-304
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    • 2005
  • Cardiac hypertrophy contributes an increased risk to major cerebrovascular events. However, the molecular mechanisms underlying cerebrovascular dysfunction during cardiac hypertrophy have not yet been characterized. In the present study, we examined the molecular mechanism of isoproterenol (ISO)-evoked activation of Ras/Raf/MAPK pathways as well as PKA activity in cerebral artery of rabbits, and we also studied whether the activations of these signaling pathways were altered in cerebral artery, during ISO-induced cardiac hypertrophy compared to heart itself. The results show that the mRNA level of c-fos (not c-jun and c-myc) in heart and these genes in cerebral artery were considerably increased during cardiac hypertrophy. These results that the PKA activity and activations of Ras/Raf/ERK cascade as well as c-fos expression in rabbit heart during cardiac hypertrophy were consistent with previous reports. Interestingly, however, we also showed a novel finding that the decreased PKA activity might have differential effects on Ras and Raf expression in cerebral artery during cardiac hypertrophy. In conclusion, there are differences in molecular mechanisms between heart and cerebral artery during cardiac hypertrophy when stimulated with β2 adrenoreceptor (AR), suggesting a possible mechanism underlying cerebrovascular dysfunction during cardiac hypertrophy.

Wolman Disease

  • Baek, Gyeong-Hun;Kim, Jun-Seong;Jin, Dong-Gyu
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.2 no.1
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    • pp.25-28
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    • 2002
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Application of metabolic profiling for biomarker discovery

  • Hwang, Geum-Sook
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2007.11a
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    • pp.19-27
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    • 2007
  • An important potential of metabolomics-based approach is the possibility to develop fingerprints of diseases or cellular responses to classes of compounds with known common biological effect. Such fingerprints have the potential to allow classification of disease states or compounds, to provide mechanistic information on cellular perturbations and pathways and to identify biomarkers specific for disease severity and drug efficacy. Metabolic profiles of biological fluids contain a vast array of endogenous metabolites. Changes in those profiles resulting from perturbations of the system can be observed using analytical techniques, such as NMR and MS. $^1H$ NMR was used to generate a molecular fingerprint of serum or urinary sample, and then pattern recognition technique was applied to identity molecular signatures associated with the specific diseases or drug efficiency. Several metabolites that differentiate disease samples from the control were thoroughly characterized by NMR spectroscopy. We investigated the metabolic changes in human normal and clinical samples using $^1H$ NMR. Spectral data were applied to targeted profiling and spectral binning method, and then multivariate statistical data analysis (MVDA) was used to examine in detail the modulation of small molecule candidate biomarkers. We show that targeted profiling produces robust models, generates accurate metabolite concentration data, and provides data that can be used to help understand metabolic differences between healthy and disease population. Such metabolic signatures could provide diagnostic markers for a disease state or biomarkers for drug response phenotypes.

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Analysis of Research Trend about Jowiseungcheong-tang (Diàowèishēngqīng-tāng) for Treating Obesity and Metabolic Disease: Focused on Domestic Journals (조위승청탕(調胃升淸湯)의 비만 및 대사성 질환에 대한 연구동향 분석: 국내 학술지를 중심으로)

  • Lee, Soohwan;Lee, Wonjun;Jeong, Jihong;Cha, Yunyeop
    • Journal of Korean Medicine Rehabilitation
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    • v.31 no.4
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    • pp.13-23
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    • 2021
  • Objectives The purpose of this research is to comprehensively analyze about Jowiseungcheong-tang (Diàowèishēngqīng-tāng). This herbal medicine is widely used to treat obesity and metabolic disease. Methods We used 3 search terms, 'Jowiseungcheong-tang', 'Jowiseungcheong-tang plus obesity' and 'Jowiseungcheong-tang plus metabolic disease' in Korean word via 5 domestic databases. Therefore, 8 laboratory experiments and 4 clinical researches were chosen. Results Jowiseungcheong-tang (Diàowèishēngqīng-tāng) was identified as a herbal medicine for obesity and related metabolic disease. In plasma level of lipid, leptin, inflammatory material were decreased in laboratory experiments. Weight loss and symptom relief were reported in clinical research. Conclusions Definite information about laboratory experiment was showed, specifically suitable index and numerical value. In clinical research, although Jowiseungcheong-tang (Diàowèishēngqīng-tāng) is widely used for obesity and metabolic disease, the number of reported thesis and patient were pretty a few. Also, diagnosis methods were also scanty. Multi-institutional clinical trial should be progressed.