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      New method for quantification of gasotransmitter hydrogen sulfide in biological matrices by LC-MS/MS

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          Abstract

          Hydrogen sulfide exists widely in mammalian tissues and plays a vital role in physiological and pathophysiological processes. However, striking differences with orders of magnitude were observed for the detected hydrogen sulfide concentrations in biological matrices among different measurements in literature, which lead to the uncertainty for examination the biological relevance of hydrogen sulfide. Here, we developed and validated a liquid chromatography- mass spectrometry (LC-MS/MS) method for the determination of hydrogen sulfide in various biological matrices by determination of a derivative of hydrogen sulfide and monobromobimane named sulfide dibimane (SDB). 36S-labeled SDB was synthesized and validated for using as an internal standard. This method has been successfully used to measure hydrogen sulfide levels in a broad range of biological matrices, such as blood, plasma, tissues, cells, and enzymes, across different species. Moreover, a novel mode that hydrogen sulfide could loosely and non-covalently bind to human serum protein (HSA) and hemoglobin (HB) was revealed by using the developed method.

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          Most cited references38

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          Two's company, three's a crowd: can H2S be the third endogenous gaseous transmitter?

          Rui Wang (2002)
          Bearing the public image of a deadly "gas of rotten eggs," hydrogen sulfide (H2S) can be generated in many types of mammalian cells. Functionally, H2S has been implicated in the induction of hippocampal long-term potentiation, brain development, and blood pressure regulation. By acting specifically on KATP channels, H2S can hyperpolarize cell membranes, relax smooth muscle cells, or decrease neuronal excitability. The endogenous metabolism and physiological functions of H2S position this gas well in the novel family of endogenous gaseous transmitters, termed "gasotransmitters." It is hypothesized that H2S is the third endogenous signaling gasotransmitter, besides nitric oxide and carbon monoxide. This positioning of H2S will open an exciting field-H2S physiology-encompassing realization of the interaction of H2S and other gasotransmitters, sulfurating modification of proteins, and the functional role of H2S in multiple systems. It may shed light on the pathogenesis of many diseases related to the abnormal metabolism of H2S.
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            Hydrogen sulfide-based therapeutics: exploiting a unique but ubiquitous gasotransmitter.

            Hydrogen sulfide (H2S) has become recognized as an important signalling molecule throughout the body, contributing to many physiological and pathological processes. In recent years, improved methods for measuring H2S levels and the availability of a wider range of H2S donors and more selective inhibitors of H2S synthesis have helped to more accurately identify the many biological effects of this highly reactive gaseous mediator. Animal studies of several H2S-releasing drugs have demonstrated considerable promise for the safe treatment of a wide range of disorders. Several such drugs are now in clinical trials.
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              Gasotransmitters in cancer: from pathophysiology to experimental therapy.

              The three endogenous gaseous transmitters - nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) - regulate a number of key biological functions. Emerging data have revealed several new mechanisms for each of these three gasotransmitters in tumour biology. It is now appreciated that they show bimodal pharmacological character in cancer, in that not only the inhibition of their biosynthesis but also elevation of their concentration beyond a certain threshold can exert anticancer effects. This Review discusses the role of each gasotransmitter in cancer and the effects of pharmacological agents - some of which are in early-stage clinical studies - that modulate the levels of each gasotransmitter. A clearer understanding of the pharmacological character of these three gases and the mechanisms underlying their biological effects is expected to guide further clinical translation.
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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                13 April 2017
                2017
                : 7
                : 46278
                Affiliations
                [1 ]Department of Clinical Pharmacology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine , Shanghai, China
                [2 ]State Key Laboratory of Quality Research in Chinese Medicine and School of Pharmacy, Macau University of Science and Technology , Macau
                [3 ]Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University , Shanghai, China
                [4 ]Department of Physiology, Hebei Medical University , Hebei, China
                [5 ]Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University , Shanghai, China
                [6 ]Institutes of Biological Sciences, Fudan University , Shanghai, China
                [7 ]State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University , Shanghai, China
                [8 ]Department of Cardiothoracic Surgery, Huashan Hospital of Fudan University , Shanghai, China
                [9 ]Analysis Center, School of Pharmacy, Fudan University , Shanghai, China
                [10 ]Instrumental Analysis Center, Shanghai University of Traditional Chinese Medicine , Shanghai, China
                Author notes
                Article
                srep46278
                10.1038/srep46278
                5390247
                28406238
                3603e8d5-d45d-4a3d-9a12-3507dab05114
                Copyright © 2017, The Author(s)

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 04 January 2017
                : 13 March 2017
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