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2015 ; 172
(6
): 1516-32
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Interactions of hydrogen sulfide with myeloperoxidase
#MMPMID24824874
Pálinkás Z
; Furtmüller PG
; Nagy A
; Jakopitsch C
; Pirker KF
; Magierowski M
; Jasnos K
; Wallace JL
; Obinger C
; Nagy P
Br J Pharmacol
2015[Mar]; 172
(6
): 1516-32
PMID24824874
show ga
BACKGROUND AND PURPOSE: The actions of hydrogen sulfide in human physiology have
been extensively studied and, although it is an essential mediator of many
biological functions, the underlying molecular mechanisms of its actions are
ill-defined. To elucidate the roles of sulfide in inflammation, we have
investigated its interactions with human myeloperoxidase (MPO), a major
contributor to inflammatory oxidative stress. EXPERIMENTAL APPROACH: The
interactions of sulfide and MPO were investigated using electron paramagnetic
resonance, electronic circular dichroism, UV-vis and stopped-flow spectroscopies.
KEY RESULTS: We found favourable reactions between sulfide and the native-ferric
enzyme as well as the MPO redox intermediates, ferrous MPO, compound I and
compound II. Sulfide was a potent reversible inhibitor of MPO enzymic activity
with an IC50 of 1?µM. In addition, the measured second-order rate constants for
the reactions of sulfide with compound I [k = (1.1 ± 0.06) × 10(6) ?M(-1) ?s(-1)]
and compound II [k = (2.0 ± 0.03) × 10(5) ?M(-1) ?s(-1)] suggest that sulfide is
a potential substrate for MPO?in vivo. CONCLUSION AND IMPLICATIONS: Endogenous
levels of sulfide are likely to inhibit the activity of circulating and
endothelium-bound MPO. The fully reversible inhibition suggests a mediatory role
of sulfide on the oxidant-producing function of the enzyme. Furthermore, the
efficient HOCl oxidation of sulfide to give polysulfides (recently recognized as
important components of sulfide biology) together with MPO-catalysed sulfide
oxidation and the lack of interaction between MPO and sulfide oxidation products,
predict a modulatory role of MPO in sulfide signalling.
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