TY - JOUR
T1 - Polysulfide stabilization by tyrosine and hydroxyphenyl-containing derivatives that is important for a reactive sulfur metabolomics analysis
AU - Hamid, Hisyam Abdul
AU - Tanaka, Akira
AU - Ida, Tomoaki
AU - Nishimura, Akira
AU - Matsunaga, Tetsuro
AU - Fujii, Shigemoto
AU - Morita, Masanobu
AU - Sawa, Tomohiro
AU - Fukuto, Jon M.
AU - Nagy, Péter
AU - Tsutsumi, Ryohei
AU - Motohashi, Hozumi
AU - Ihara, Hideshi
AU - Akaike, Takaaki
N1 - Funding Information:
This work was supported in part by a Grant-in-Aid for Scientific Research ( 18H05277 to T.A.) and a Grant-in-Aid for Scientific Research on Innovative Areas ( 26111008 to T.A.) from the Ministry of Education, Sciences, Sports and Technology ( MEXT ), Japan; and The Hungarian National Research, Development and Innovation Office (Nr. KH17 126766 and K129286 to P.N.).
Publisher Copyright:
© 2019 The Authors
PY - 2019/2
Y1 - 2019/2
N2 - The physiological importance of reactive sulfur species (RSS) such as cysteine hydropersulfide (CysSSH) has been increasingly recognized in recent years. We have established a reactive sulfur metabolomics analysis by using RSS metabolic profiling, which revealed appreciable amounts of RSS generated endogenously and ubiquitously in both prokaryotic and eukaryotic organisms. The chemical nature of these polysulfides is not fully understood, however, because of their reactive or complicated redox-active properties. In our study here, we determined that tyrosine and a hydroxyphenyl-containing derivative, β-(4-hydroxyphenyl)ethyl iodoacetamide (HPE-IAM), had potent stabilizing effects on diverse polysulfide residues formed in CysSSH-related low-molecular-weight species, e.g., glutathione polysulfides (oxidized glutathione trisulfide and oxidized glutathione tetrasulfide). The protective effect against degradation was likely caused by the inhibitory activity of hydroxyphenyl residues of tyrosine and HPE-IAM against alkaline hydrolysis of polysulfides. This hydrolysis occurred via heterolytic scission triggered by the hydroxyl anion acting on polysulfides that are cleaved into thiolates and sulfenic acids, with the hydrolysis being enhanced by alkylating reagents (e.g. IAM) and dimedone. Moreover, tyrosine prevented electrophilic degradation occurring in alkaline pH. The polysulfide stabilization induced by tyrosine or the hydroxyphenyl moiety of HPE-IAM will greatly improve our understanding of the chemical properties of polysulfides and may benefit the sulfur metabolomics analysis if it can be applied successfully to any kind of biological samples, including clinical specimens.
AB - The physiological importance of reactive sulfur species (RSS) such as cysteine hydropersulfide (CysSSH) has been increasingly recognized in recent years. We have established a reactive sulfur metabolomics analysis by using RSS metabolic profiling, which revealed appreciable amounts of RSS generated endogenously and ubiquitously in both prokaryotic and eukaryotic organisms. The chemical nature of these polysulfides is not fully understood, however, because of their reactive or complicated redox-active properties. In our study here, we determined that tyrosine and a hydroxyphenyl-containing derivative, β-(4-hydroxyphenyl)ethyl iodoacetamide (HPE-IAM), had potent stabilizing effects on diverse polysulfide residues formed in CysSSH-related low-molecular-weight species, e.g., glutathione polysulfides (oxidized glutathione trisulfide and oxidized glutathione tetrasulfide). The protective effect against degradation was likely caused by the inhibitory activity of hydroxyphenyl residues of tyrosine and HPE-IAM against alkaline hydrolysis of polysulfides. This hydrolysis occurred via heterolytic scission triggered by the hydroxyl anion acting on polysulfides that are cleaved into thiolates and sulfenic acids, with the hydrolysis being enhanced by alkylating reagents (e.g. IAM) and dimedone. Moreover, tyrosine prevented electrophilic degradation occurring in alkaline pH. The polysulfide stabilization induced by tyrosine or the hydroxyphenyl moiety of HPE-IAM will greatly improve our understanding of the chemical properties of polysulfides and may benefit the sulfur metabolomics analysis if it can be applied successfully to any kind of biological samples, including clinical specimens.
KW - Reactive sulfur metabolomics analysis
KW - Reactive sulfur signaling
KW - Reactive sulfur species
KW - Redox signaling
KW - Tyrosine
KW - β-(4-Hydroxyphenyl)ethyl iodoacetamide
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U2 - 10.1016/j.redox.2019.101096
DO - 10.1016/j.redox.2019.101096
M3 - Article
C2 - 30634125
AN - SCOPUS:85059565629
VL - 21
JO - Redox Biology
JF - Redox Biology
SN - 2213-2317
M1 - 101096
ER -