SIRT4-mediated deacetylation of PRDX3 attenuates liver ischemia reperfusion injury by suppressing ferroptosis
Abstract
Liver
ischemia-reperfusion
injury
(LIRI)
is
an
important
cause
of
the
clinical
prognosis
liver
transplantation.
Despite
diverse
roles
that
Sirtuin
4
(SIRT4)
plays
in
posttranslational
modifications,
its
specific
involvement
onset
and
progression
LIRI
remains
unclear.
The
aim
this
research
was
to
investigate
influence
SIRT4
on
pathogenesis
LIRI.
In
study,
knockout
liver-specific
overexpression
mice
AML12
cells
were
used
possible
role
Here,
we
showed
expression
downregulated
with
or
exposed
H/R
tissue
transplant
patients.
deletion
led
exacerbation
ferroptosis;
conversely,
produced
opposite
results.
Furthermore,
ferroptosis
inhibitor
ferrostatin-1
counteracted
caused
by
knockout.
Mechanistically,
interacted
Peroxiredoxins
(PRDX3)
deacetylated
it
at
lysine
92,
leading
inhibition
PRDX3
hyper-oxidation
ferroptosis.
protective
effect
dependent
deacetylation
K92.
Finally,
developed
a
liver-targeted
Lipid
nanoparticles
(LNP)-sirt4
mRNA
alleviated
I/R
mice.
Taken
together,
these
results
indicate
SIRT4‒PRDX3
axis
key
may
be
therapeutic
target
for
treatment
Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 15, 2024
Language: Английский