3 research outputs found
Chemical Characterization of the Smallest <i>S</i>-Nitrosothiol, HSNO; Cellular Cross-talk of H<sub>2</sub>S and <i>S</i>-Nitrosothiols
Dihydrogen sulfide recently emerged as a biological signaling
molecule
with important physiological roles and significant pharmacological
potential. Chemically plausible explanations for its mechanisms of
action have remained elusive, however. Here, we report that H<sub>2</sub>S reacts with <i>S</i>-nitrosothiols to form thionitrous
acid (HSNO), the smallest <i>S</i>-nitrosothiol. These results
demonstrate that, at the cellular level, HSNO can be metabolized to
afford NO<sup>+</sup>, NO, and NO<sup>–</sup> species, all
of which have distinct physiological consequences of their own. We
further show that HSNO can freely diffuse through membranes, facilitating
transnitrosation of proteins such as hemoglobin. The data presented
in this study explain some of the physiological effects ascribed to
H<sub>2</sub>S, but, more broadly, introduce a new signaling molecule,
HSNO, and suggest that it may play a key role in cellular redox regulation
Cytochrome <i>c</i> Reduction by H<sub>2</sub>S Potentiates Sulfide Signaling
Hydrogen
sulfide (H<sub>2</sub>S) is an endogenously produced gas that is toxic
at high concentrations. It is eliminated by a dedicated mitochondrial
sulfide oxidation pathway, which connects to the electron transfer
chain at the level of complex III. Direct reduction of cytochrome <i>c</i> (Cyt C) by H<sub>2</sub>S has been reported previously
but not characterized. In this study, we demonstrate that reduction
of ferric Cyt C by H<sub>2</sub>S exhibits hysteretic behavior, which
suggests the involvement of reactive sulfur species in the reduction
process and is consistent with a reaction stoichiometry of 1.5 mol
of Cyt C reduced/mol of H<sub>2</sub>S oxidized. H<sub>2</sub>S increases
O<sub>2</sub> consumption by human cells (HT29 and HepG2) treated
with the complex III inhibitor antimycin A, which is consistent with
the entry of sulfide-derived electrons at the level of complex IV.
Cyt C-dependent H<sub>2</sub>S oxidation stimulated protein persulfidation
in vitro, while silencing of Cyt C expression decreased mitochondrial
protein persulfidation in a cell culture. Cyt C released during apoptosis
was correlated with persulfidation of procaspase 9 and with loss of
its activity. These results reveal a potential role for the electron
transfer chain in general, and Cyt C in particular, for potentiating
sulfide-based signaling
Nitric Oxide Is Reduced to HNO by Proton-Coupled Nucleophilic Attack by Ascorbate, Tyrosine, and Other Alcohols. A New Route to HNO in Biological Media?
The role of NO in biology is well
established. However, an increasing
body of evidence suggests that azanone (HNO), could also be involved
in biological processes, some of which are attributed to NO. In this
context, one of the most important and yet unanswered questions is
whether and how HNO is produced in vivo. A possible route concerns
the chemical or enzymatic reduction of NO. In the present work, we
have taken advantage of a selective HNO sensing method, to show that
NO is reduced to HNO by biologically relevant alcohols with moderate
reducing capacity, such as ascorbate or tyrosine. The proposed mechanism
involves a nucleophilic attack to NO by the alcohol, coupled to a
proton transfer (PCNA: proton-coupled nucleophilic attack) and a subsequent
decomposition of the so-produced radical to yield HNO and an alkoxyl
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