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2015 ; 4
(5
): ä Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Hydrogen Sulfide Levels and Nuclear Factor-Erythroid 2-Related Factor 2 (NRF2)
Activity Are Attenuated in the Setting of Critical Limb Ischemia (CLI)
#MMPMID25977470
Islam KN
; Polhemus DJ
; Donnarumma E
; Brewster LP
; Lefer DJ
J Am Heart Assoc
2015[May]; 4
(5
): ä PMID25977470
show ga
BACKGROUND: Cystathionine ?-lyase, cystathionine ?-synthase, and
3-mercaptopyruvate sulfurtransferase are endogenous enzymatic sources of hydrogen
sulfide (H2S). Functions of H2S are mediated by several targets including ion
channels and signaling proteins. Nuclear factor-erythroid 2-related factor 2 is
responsible for the expression of antioxidant response element-regulated genes
and is known to be upregulated by H2S. We examined the levels of H2S,
H2S-producing enzymes, and nuclear factor-erythroid 2-related factor 2 activation
status in skeletal muscle obtained from critical limb ischemia (CLI) patients.
METHODS AND RESULTS: Gastrocnemius tissues were attained postamputation from
human CLI and healthy control patients. We found mRNA and protein levels of
cystathionine ?-lyase, cystathionine ?-synthase, and 3-mercaptopyruvate
sulfurtransferase were significantly decreased in skeletal muscle of CLI patients
as compared to control. H2S and sulfane sulfur levels were significantly
decreased in skeletal muscle of CLI patients. We also observed significant
reductions in nuclear factor-erythroid 2-related factor 2 activation as well as
antioxidant proteins, such as Cu, Zn-superoxide dismutase, catalase, and
glutathione peroxidase in skeletal muscle of CLI patients. Biomarkers of
oxidative stress, such as malondialdehyde and protein carbonyl formation, were
significantly increased in skeletal muscle of CLI patients as compared to healthy
controls. CONCLUSIONS: The data demonstrate that H2S bioavailability and nuclear
factor-erythroid 2-related factor 2 activation are both attenuated in CLI tissues
concomitant with significantly increased oxidative stress. Reductions in the
activity of H2S-producing enzymes may contribute to the pathogenesis of CLI.