• Title/Summary/Keyword: Therapeutic enzymes

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Deubiquitinating enzymes as cancer biomarkers: new therapeutic opportunities?

  • Poondla, Naresh;Chandrasekaran, Arun Pandian;Kim, Kye-Seong;Ramakrishna, Suresh
    • BMB Reports
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    • v.52 no.3
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    • pp.181-189
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    • 2019
  • Cancer remains a life-threatening disease and accounts for the major mortality rates worldwide. The practice of using biomarkers for early detection, staging, and customized therapy may increase cancer patients' survival. Deubiquitinating enzymes (DUBs) are a family of proteases that remove ubiquitin tags from proteins of interest undergoing proteasomal degradation. DUBs play several functional roles other than deubiquitination. One of the important roles of DUBs is regulation of tumor progression. Several reports have suggested that the DUB family members were highly-elevated in various cancer cells and tissues in different stages of cancer. These findings suggest that the DUBs could be used as drug targets in cancer therapeutics. In this review, we recapitulate the role of the DUB family members, including ubiquitin-specific protease, otubain protease, and important candidates from other family members. Our aim was to better understand the connection between DUB expression profiles and cancers to allow researchers to design inhibitors or gene therapies to improve diagnosis and prognosis of cancers.

The role of peroxidases in the pathogenesis of atherosclerosis

  • Park, Jong-Gil;Oh, Goo-Taeg
    • BMB Reports
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    • v.44 no.8
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    • pp.497-505
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    • 2011
  • Reactive oxygen species (ROS), which include superoxide anions and peroxides, induce oxidative stress, contributing to the initiation and progression of cardiovascular diseases involving atherosclerosis. The endogenous and exogenous factors hypercholesterolemia, hyperglycemia, hypertension, and shear stress induce various enzyme systems such as nicotinamide adenine dinucleotide (phosphate) oxidase, xanthine oxidase, and lipoxygenase in vascular and immune cells, which generate ROS. Besides inducing oxidative stress, ROS mediate signaling pathways involved in monocyte adhesion and infiltration, platelet activation, and smooth muscle cell migration. A number of antioxidant enzymes (e.g., superoxide dismutases, catalase, glutathione peroxidases, and peroxiredoxins) regulate ROS in vascular and immune cells. Atherosclerosis results from a local imbalance between ROS production and these antioxidant enzymes. In this review, we will discuss 1) oxidative stress and atherosclerosis, 2) ROS-dependent atherogenic signaling in endothelial cells, macrophages, and vascular smooth muscle cells, 3) roles of peroxidases in atherosclerosis, and 4) antioxidant drugs and therapeutic perspectives.

Biomedicinal implications of high-density lipoprotein: its composition, structure, functions, and clinical applications

  • Cho, Kyung-Hyun
    • BMB Reports
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    • v.42 no.7
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    • pp.393-400
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    • 2009
  • High-density lipoprotein (HDL) is a proven biomarker for the monitoring of changes in antioxidant and anti-inflammation capability of body fluids. The beneficial virtues of HDL are highly dependent on its lipids and protein compositions, and their ratios. In normal state, the HDL particle is enriched with lipids and several HDL-associated enzymes, which are responsible for its antioxidant activity. Lower HDL-cholesterol levels (<40 mg/dL) have been recognized as an independent risk factor for coronary artery disease, as well as being a known component of metabolic syndrome. Functional and structural changes of HDL have been recognized as factors pivotal to the evaluation of HDL-quality. In this review, I have elected to focus on the functional and structural correlations of HDL and the roles of HDL-associated apolipoproteins and enzymes. Recent clinical applications of HDL have also been reviewed, particularly the therapeutic targeting of HDL metabolism and reconstituted HDL; these techniques represent promising emerging strategies for the treatment of cardiovascular disease, for drug or gene therapy.

Upstream Regulators and Downstream Effectors of NADPH Oxidases as Novel Therapeutic Targets for Diabetic Kidney Disease

  • Gorin, Yves;Wauquier, Fabien
    • Molecules and Cells
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    • v.38 no.4
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    • pp.285-296
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    • 2015
  • Oxidative stress has been linked to the pathogenesis of diabetic nephropathy, the complication of diabetes in the kidney. NADPH oxidases of the Nox family, and in particular the homologue Nox4, are a major source of reactive oxygen species in the diabetic kidney and are critical mediators of redox signaling in glomerular and tubulointerstitial cells exposed to the diabetic milieu. Here, we present an overview of the current knowledge related to the understanding of the role of Nox enzymes in the processes that control mesangial cell, podocyte and tubulointerstitial cell injury induced by hyperglycemia and other predominant factors enhanced in the diabetic milieu, including the renin-angiotensin system and transforming growth factor-${\beta}$. The nature of the upstream modulators of Nox enzymes as well as the downstream targets of the Nox NADPH oxidases implicated in the propagation of the redox processes that alter renal biology in diabetes will be highlighted.

The Effect of Natural Mate Tea Extract on the Body Weight and Biochemical Biomarker in High Fat Diet-Obese(ob/ob) Mice (천연마테차 물추출물의 고지방식이 비만쥐의 체중과 생화학적 변화에 미치는 영향)

  • Kim, Sang-Tae;Hwang, Cho-Won;Kim, Young-Kyoon
    • YAKHAK HOEJI
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    • v.56 no.1
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    • pp.1-8
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    • 2012
  • In this study, we investigated the anti-obese activity of sevennight extract in high fat diet-ob/ob C57BL/6J mice by oral administered for 1 weeks. Mate water extract (MATEWi) was found to lower whole body and epididymal adipose tissue weights and lowered plasma levels of triglyceride (TG) and total cholesterol (TC), HDL and LDL, compared to those in high fat fed ob/ob group. These results suggest that Mate extract ameliorates obesity through activation of lipogenic enzymes and FA oxidation resulting from phosphorylation of AKT and GSK-$3{\beta}$, and could be developed as a potential therapeutic agent for obese mices.

Critical Roles of Deubiquitinating Enzymes in the Nervous System and Neurodegenerative Disorders

  • Das, Soumyadip;Ramakrishna, Suresh;Kim, Kye-Seong
    • Molecules and Cells
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    • v.43 no.3
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    • pp.203-214
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    • 2020
  • Post-translational modifications play major roles in the stability, function, and localization of target proteins involved in the nervous system. The ubiquitin-proteasome pathway uses small ubiquitin molecules to degrade neuronal proteins. Deubiquitinating enzymes (DUBs) reverse this degradation and thereby control neuronal cell fate, synaptic plasticity, axonal growth, and proper function of the nervous system. Moreover, mutations or downregulation of certain DUBs have been found in several neurodegenerative diseases, as well as gliomas and neuroblastomas. Based on emerging findings, DUBs represent an important target for therapeutic intervention in various neurological disorders. Here, we summarize advances in our understanding of the roles of DUBs related to neurobiology.

Function of gaseous hydrogen sulfide in liver fibrosis

  • Lee, Jae-Ho;Im, Seung-Soon
    • BMB Reports
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    • v.55 no.10
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    • pp.481-487
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    • 2022
  • Over the past few years, hydrogen sulfide (H2S) has been shown to exert several biological functions in mammalian. The endogenous production of H2S is mainly mediated by cystathione β-synthase, cystathione γ-lyase and 3-mercaptopyruvate sulfur transferase. These enzymes are broadly expressed in liver tissue and regulates liver function by working on a variety of molecular targets. As an important regulator of liver function, H2S is critically involved in the pathogenesis of various liver diseases, such as non-alcoholic steatohepatitis and liver cancer. Targeting H2S-generating enzymes may be a therapeutic strategy for controlling liver diseases. This review described the function of H2S in liver disease and summarized recent characterized role of H2S in several cellular process of the liver.

Apoptosis in Cancer - An Update

  • Sankari, S. Leena;Masthan, K.M.K.;Babu, N. Aravindha;Bhattacharjee, Tathagata;Elumalai, M.
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.10
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    • pp.4873-4878
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    • 2012
  • Apoptosis is programmed cell death which is essential for development and survival of living organisms. It is a sequentially regulated suicidal programme where cells activate certain enzymes which dissolute their own nuclear component and various protein component of nucleus and cytoplasm. Disturbance of this regulatory pathway may lead to various diseases like autoimmune diseases, neurodegenerative diseases and cancers. The potential mechanisms of apoptosis and its role in cancer are discussed. The ability of apoptosis to modulate the life or death of a cell is also recognized for its immense therapeutic potential. Understanding the mechanisms from this review will give us better insight to the pathogenesis of various diseases including cancer and will open new horizons to therapeutic approaches.

Characterization of Erythropoietin Producing Cell Lines after Introduction of Urea Cycle Enzymes, Carbamoly Phosphate Synthetase and Ornithine Transcarbamoylase

  • Lee, Yun-Jeong;Kim, Na-Young;Kim, Hyung-Jin;Park, Jung-Ho;Kim, Jung-Kwon;Hee, Chang-Kern;Kim, Jung-Hoe;Kim, Hong-Jin
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.170.3-171
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    • 2003
  • An efficient Erythropoietin (EPO)-expression system in mammalian cells is required for massive production for therapeutic use. Ammonium ion is a major problem in the production of valuable recombinant proteins in cultured animal cells. Therefore, it is of importance to devise a system by which a high productivity of human therapeutic recombinant protein can be maintained or enhanced under low ammonium concentration. To reduce the ammonium ion accumulated in EPO producing Chinese Hamster Ovary (CHO) ceels, IBE, we introduced the first two genes of the urea cycle, carbamoyl phosphate synthetase (CPSI) and arnithine transcarbamoylase (OTC), into IBE using a stable transfection method. (omitted)

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GC-MS Analysis of Ricinus communis, Pongamia pinnata, Datura metal, Azadirachta indica, Acalypha indica (leaf) Extract Using Methanol Extraction

  • J. Varshini premakumari;M. Job Gopinath
    • Mass Spectrometry Letters
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    • v.14 no.3
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    • pp.79-90
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    • 2023
  • Natural goods, especially therapeutic plants, are abundant in the World. Because they have the ability to provide all humanity with countless advantages as a source of medicines, medicinal plants are presently receiving more attention than ever. These plants' therapeutic efficacy is based on bioactive phytochemical components that have clear physiological effects on the human body. The drying process is crucial for the preparation of plant materials prior to extraction since freshly harvested plant materials include active enzymes that create active components, intermediates, and metabolic processes. Many of the phytoconstituents may be extracted using the semi-polar solvent methanol. The goal of the current work is to use the GC-MS gas chromatography- mass spectrometry technology to identify the phytochemicals and review their biological activity. In methanol leaf extract, 5 phytocompounds were found in Ricinus communis, 5 phytocompounds in Pongamia pinnata, 12 phytocompounds in Datura metal, 7 phytocompounds in Azadirachta indica, 11 phytocompounds in Acalypha indica.