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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Free+Radic+Biol+Med
2015 ; 88
(Pt B
): 391-403
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gab.com Text
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English Wikipedia
Respiratory syncytial virus infection down-regulates antioxidant enzyme
expression by triggering deacetylation-proteasomal degradation of Nrf2
#MMPMID26073125
Komaravelli N
; Tian B
; Ivanciuc T
; Mautemps N
; Brasier AR
; Garofalo RP
; Casola A
Free Radic Biol Med
2015[Nov]; 88
(Pt B
): 391-403
PMID26073125
show ga
Respiratory syncytial virus (RSV) is the most important cause of viral acute
respiratory tract infections and hospitalizations in children, for which no
vaccine or treatment is available. RSV infection in cells, mice, and children
leads to rapid generation of reactive oxygen species, which are associated with
oxidative stress and lung damage, due to a significant decrease in the expression
of airway antioxidant enzymes (AOEs). Oxidative stress plays an important role in
the pathogenesis of RSV-induced lung disease, as antioxidants ameliorate clinical
disease and inflammation in vivo. The aim of this study is to investigate the
unknown mechanism(s) of virus-induced inhibition of AOE expression. RSV infection
is shown to induce a progressive reduction in nuclear and total cellular levels
of the transcription factor NF-E2-related factor 2 (Nrf2), resulting in decreased
binding to endogenous AOE gene promoters and decreased AOE expression. RSV
induces Nrf2 deacetylation and degradation via the proteasome pathway in vitro
and in vivo. Histone deacetylase and proteasome inhibitors block Nrf2 degradation
and increase Nrf2 binding to AOE endogenous promoters, resulting in increased AOE
expression. Known inducers of Nrf2 are able to increase Nrf2 activation and
subsequent AOE expression during RSV infection in vitro and in vivo, with
significant amelioration of oxidative stress. This is the first study to
investigate the mechanism(s) of virus-induced inhibition of AOE expression.
RSV-induced inhibition of Nrf2 activation, due to deacetylation and proteasomal
degradation, could be targeted for therapeutic intervention aimed to increase
airway antioxidant capacity during infection.