Cystathionine-β-Synthase: Molecular Regulation and Pharmacological Inhibition.
Karim Zuhra,Fiona Augsburger,Tomas Majtan,Csaba Szabó +3 more
- Vol. 10, Iss: 5, pp 697
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TLDR
Among the small-molecule CBS inhibitors, the review highlights the specificity and selectivity problems related to many of the commonly used “CBS inhibitors” and provides a comprehensive review of their pharmacological actions under physiological conditions and in various disease models.Abstract:
Cystathionine-β-synthase (CBS), the first (and rate-limiting) enzyme in the transsulfuration pathway, is an important mammalian enzyme in health and disease. Its biochemical functions under physiological conditions include the metabolism of homocysteine (a cytotoxic molecule and cardiovascular risk factor) and the generation of hydrogen sulfide (H2S), a gaseous biological mediator with multiple regulatory roles in the vascular, nervous, and immune system. CBS is up-regulated in several diseases, including Down syndrome and many forms of cancer; in these conditions, the preclinical data indicate that inhibition or inactivation of CBS exerts beneficial effects. This article overviews the current information on the expression, tissue distribution, physiological roles, and biochemistry of CBS, followed by a comprehensive overview of direct and indirect approaches to inhibit the enzyme. Among the small-molecule CBS inhibitors, the review highlights the specificity and selectivity problems related to many of the commonly used "CBS inhibitors" (e.g., aminooxyacetic acid) and provides a comprehensive review of their pharmacological actions under physiological conditions and in various disease models.read more
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Hydrogen sulfide: An endogenous regulator of the immune system.
TL;DR: Low, regulated amounts of H2S, when therapeutically delivered by small molecule donors, improve the function of various immune cells, and protect them against dysfunction induced by various noxious stimuli (e.g. reactive oxygen species or oxidized LDL).
Journal ArticleDOI
Physiological roles of hydrogen sulfide in mammalian cells, tissues and organs.
TL;DR: A wide array of significant roles of H2S in the physiological regulation of all organ functions emerges from this review.
Journal ArticleDOI
Hydrogen Sulfide, an Endogenous Stimulator of Mitochondrial Function in Cancer Cells.
TL;DR: In this paper, the state-of-the-art knowledge regarding the mitochondrial functions of endogenously produced H2S in cancer cells is presented, including the maintenance of mitochondrial organization and repair of mitochondrial DNA repair.
Journal ArticleDOI
Near-Infrared Fluorescent Probe with a Large Stokes Shift for Detection of Hydrogen Sulfide in Food Spoilage, Living Cells, and Zebrafish.
TL;DR: In this paper , an NIR fluorescent turn-on responding probe (DDM-H2S) with a large Stokes shift (190 nm) was designed and synthesized for the detection of H2S.
Journal ArticleDOI
Inhibition of hydrogen sulfide synthesis reverses acquired resistance to 5-FU through miR-215-5p-EREG/TYMS axis in colon cancer cells.
Shanwen Chen,Taohua Yue,Zhihao Huang,Jing Zhu,Dingfang Bu,Xin Wang,Yisheng Pan,Yucun Liu,Pengyuan Wang +8 more
TL;DR: It is demonstrated that inhibiting H2S synthesis can reverse the acquired resistance to 5-FU in colon cancer cells.
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Jesper V. Olsen,Michiel Vermeulen,Anna Santamaria,Chanchal Kumar,Martin L. Miller,Martin L. Miller,Lars Juhl Jensen,Florian Gnad,Jürgen Cox,Thomas Skøt Jensen,Erich A. Nigg,Søren Brunak,Søren Brunak,Matthias Mann +13 more
TL;DR: High-resolution mass spectrometry–based proteomics was applied to investigate the proteome and phosphoproteome of the human cell cycle on a global scale and quantified 6027 proteins and 20,443 unique phosphorylation sites and their dynamics, finding that nuclear proteins and proteins involved in regulating metabolic processes have high phosphorylated site occupancy in mitosis, suggesting that these proteins may be inactivated by phosphorylate in mitotic cells.