Abstract:Protein S-nitrosation is an important consequence of NO●·metabolism with implications in physiology and pathology. The mechanisms responsible for S-nitrosation in vivo remain debatable and kinetic data on protein S-nitrosation by different agents are limited. 2-Cys peroxiredoxins, in particular Prx1 and Prx2, were detected as being S-nitrosated in multiple mammalian cells under a variety of conditions. Here, we investigated the kinetics of Prx1 S-nitrosation by nitrosoglutathione (GSNO), a recognized biologica… Show more
“…radicals. According to the authors of a recently published work [ 57 ], those radicals could be bound with NO molecules, which, for instance, are released from DNICs with the formation of the corresponding S-nitrosothiols. In other words, excess of thiols could trigger a sequence of reactions shown on Scheme 8 : Scheme 8.…”
Section: Discussionmentioning
confidence: 99%
“…The validity of another viewpoint of our opponents [43][44][45][46][47] will be described below. b) and the EPR spectra of aqueous solutions of DNIC with cysteine containing 14 NO (curves c and d) or 15 NO (curves e and f) or 57 Fe (curves g and h). The EPR spectra were recorded at ambient temperatures (curves a, b, d, f and h) or at 77 K (curves c, e and g).…”
Section: Part 2 Experimental Evidence Of the Ability Of Dnics With Thiol-containing Ligands To Be Donors Of Nitrosonium Cationsmentioning
confidence: 99%
“…2). If the 57 Fe isotope with I = 1/2 is included in the complexes, the doublet HFS emerges (Fig. 2), which indicates that M-DNICS have only one atom of iron.…”
Section: Part 2 Experimental Evidence Of the Ability Of Dnics With Thiol-containing Ligands To Be Donors Of Nitrosonium Cationsmentioning
The present work provides theoretical and experimental foundations for the ability of dinitrosyl iron complexes (DNICs) with thiol
-
containing ligands to be not only the donors of neutral NO molecules, but also the donors of nitrosonium cations (NO
+
) in living organisms ensuring S-nitrosation of various proteins and low-molecular-weight compounds. It is proposed that the emergence of those cations in DNICs is related to disproportionation reaction of NO molecules, initiated by their binding with Fe
2+
ions (two NO molecules per one ion). At the same time, possible hydrolysis of iron-bound nitrosonium cations is prevented by the electron density transition to nitrosonium cations from sulfur atoms of thiol-containing ligands, which are included in the coordination sphere of iron. It allows supposing that iron in iron–nitrosyl complexes of DNICs has a
d
7
electronic configuration. This supposition is underpinned by experimental data revealing that a half of nitrosyl ligands are converted into S-nitrosothiols (RSNOs) when those complexes decompose, with the other half of those ligands released in the form of neutral NO molecules.
“…radicals. According to the authors of a recently published work [ 57 ], those radicals could be bound with NO molecules, which, for instance, are released from DNICs with the formation of the corresponding S-nitrosothiols. In other words, excess of thiols could trigger a sequence of reactions shown on Scheme 8 : Scheme 8.…”
Section: Discussionmentioning
confidence: 99%
“…The validity of another viewpoint of our opponents [43][44][45][46][47] will be described below. b) and the EPR spectra of aqueous solutions of DNIC with cysteine containing 14 NO (curves c and d) or 15 NO (curves e and f) or 57 Fe (curves g and h). The EPR spectra were recorded at ambient temperatures (curves a, b, d, f and h) or at 77 K (curves c, e and g).…”
Section: Part 2 Experimental Evidence Of the Ability Of Dnics With Thiol-containing Ligands To Be Donors Of Nitrosonium Cationsmentioning
confidence: 99%
“…2). If the 57 Fe isotope with I = 1/2 is included in the complexes, the doublet HFS emerges (Fig. 2), which indicates that M-DNICS have only one atom of iron.…”
Section: Part 2 Experimental Evidence Of the Ability Of Dnics With Thiol-containing Ligands To Be Donors Of Nitrosonium Cationsmentioning
The present work provides theoretical and experimental foundations for the ability of dinitrosyl iron complexes (DNICs) with thiol
-
containing ligands to be not only the donors of neutral NO molecules, but also the donors of nitrosonium cations (NO
+
) in living organisms ensuring S-nitrosation of various proteins and low-molecular-weight compounds. It is proposed that the emergence of those cations in DNICs is related to disproportionation reaction of NO molecules, initiated by their binding with Fe
2+
ions (two NO molecules per one ion). At the same time, possible hydrolysis of iron-bound nitrosonium cations is prevented by the electron density transition to nitrosonium cations from sulfur atoms of thiol-containing ligands, which are included in the coordination sphere of iron. It allows supposing that iron in iron–nitrosyl complexes of DNICs has a
d
7
electronic configuration. This supposition is underpinned by experimental data revealing that a half of nitrosyl ligands are converted into S-nitrosothiols (RSNOs) when those complexes decompose, with the other half of those ligands released in the form of neutral NO molecules.
“…The probability of this transformation of thiol-containing proteins can be very high, as upon interaction of cells and tissues with DNIC with the small molecule thiol-containing ligands, iron nitrosyl groups (Fe(NO) 2 ) are transferred from low molecular DNIC to protein thiols forming more stable protein-containing M-DNIC and B-DNIC [39,40]. Nevertheless, superoxide anions can cause complex degradation via the mechanism mentioned above [36].…”
Here we demonstrate that binuclear dinitrosyl iron complexes with thiol-containing ligands (glutathione and mercaptosuccinate, B-DNIC-GSH and B-DNIC-MS, respectively) exert cytotoxic effects on MCF7 human breast cancer cells. We showed that they are mediated by nitrosonium cations released from these complexes (NO + ). This finding is supported by the cytotoxic effect of both B-DNICs on MCF7 cells evidenced to retain or was even promoted in the presence of N-Methyl-D-glucamine dithiocarbamate (MGD). MGD recruits an iron nitrosyl group [Fe(NO)] from the iron-dinitrosyl fragment [Fe(NO) 2 ] of B-DNIC-MS forming stable mononitrosyl complexes of iron with MGD and releasing NO + cations from a [Fe(NO) 2 ] fragment.
“…This reaction is mediated by glutathionyl-DINICs and involves the reactive peroxidatic cysteinyl residue in the active site of Prx1. The reaction affects the reactivity of the protein and thus its enzymatic and signaling functions [ 165 ].…”
Section: Other Glutathione-iron Complexesmentioning
Glutathione (GSH) was initially identified and characterized for its redox properties and later for its contributions to detoxification reactions. Over the past decade, however, the essential contributions of glutathione to cellular iron metabolism have come more and more into focus. GSH is indispensable in mitochondrial iron-sulfur (FeS) cluster biosynthesis, primarily by co-ligating FeS clusters as a cofactor of the CGFS-type (class II) glutaredoxins (Grxs). GSH is required for the export of the yet to be defined FeS precursor from the mitochondria to the cytosol. In the cytosol, it is an essential cofactor, again of the multi-domain CGFS-type Grxs, master players in cellular iron and FeS trafficking. In this review, we summarize the recent advances and progress in this field. The most urgent open questions are discussed, such as the role of GSH in the export of FeS precursors from mitochondria, the physiological roles of the CGFS-type Grx interactions with BolA-like proteins and the cluster transfer between Grxs and recipient proteins.
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