Frontiers in Physiology,
Год журнала:
2023,
Номер
14
Опубликована: Апрель 6, 2023
The
prevalence
of
renal
diseases
including
acute
kidney
injury
(AKI)
and
chronic
disease
(CKD)
is
increasing
worldwide.
However,
the
pathogenesis
most
still
unclear
effective
treatments
are
lacking.
DNA
damage
related
response
(DDR)
have
been
confirmed
as
common
disease.
Reactive
oxygen
species
(ROS)
induced
one
types
involved
in
In
recent
years,
several
developments
made
field
damage.
Herein,
we
review
roles
tubular
epithelial
cell
this
review,
conclude
that
focusing
on
may
provide
valuable
diagnostic
biomarkers
treatment
strategies
for
Cardiovascular Diabetology,
Год журнала:
2022,
Номер
21(1)
Опубликована: Июнь 15, 2022
Abstract
Background
Empagliflozin
has
been
reported
to
protect
endothelial
cell
function,
regardless
of
diabetes
status.
However,
the
role
empagliflozin
in
microvascular
protection
during
myocardial
ischemia
reperfusion
injury
(I/R)
not
fully
understood.
Methods
Electron
microscopy,
western
blots,
immunofluorescence,
qPCR,
mutant
plasmid
transfection,
co-immunoprecipitation
were
employed
explore
whether
could
alleviate
damage
and
cardiac
I/R
injury.
Results
In
mice,
attenuated
injury-induced
occlusion
microthrombus
formation.
human
coronary
artery
cells,
led
adhesive
factor
upregulation,
nitric
oxide
synthase
inactivation,
focal
adhesion
kinase
downregulation,
barrier
dysfunction,
cytoskeletal
degradation
cellular
apoptosis;
however,
treatment
diminished
these
effects.
improved
mitochondrial
oxidative
stress,
respiration
adenosine
triphosphate
metabolism
I/R-treated
cells
by
preventing
phosphorylation
dynamin-related
protein
1
(Drp1)
fission
(Fis1),
thus
repressing
fission.
The
protective
effects
on
homeostasis
function
abrogated
re-introduction
phosphorylated
Fis1,
but
Drp1,
suggesting
that
Fis1
dephosphorylation
is
predominant
mechanism
whereby
inhibits
Besides,
induced
primarily
activating
DNA-dependent
catalytic
subunit
(DNA-PKcs)
pathway,
while
inactivated
this
pathway
exerting
anti-oxidative
Conclusions
These
results
demonstrated
can
microvasculature
inhibiting
DNA-PKcs/Fis1/mitochondrial
Cell Death and Disease,
Год журнала:
2023,
Номер
14(7)
Опубликована: Июль 21, 2023
Abstract
The
increase
of
lactate
is
an
independent
risk
factor
for
patients
with
sepsis-induced
acute
kidney
injury
(SAKI).
However,
whether
elevated
directly
promotes
SAKI
and
its
mechanism
remain
unclear.
Here
we
revealed
that
downregulation
the
deacetylase
Sirtuin
3
(SIRT3)
mediated
hyperacetylation
inactivation
pyruvate
dehydrogenase
E1
component
subunit
alpha
(PDHA1),
resulting
in
overproduction
renal
tubular
epithelial
cells.
We
then
found
incidence
replacement
therapy
(RRT)
septic
blood
≥
4
mmol/L
was
increased
significantly,
compared
those
<
2
mmol/L.
Further
vitro
vivo
experiments
showed
additional
administration
could
promote
SAKI.
Mechanistically,
lactylation
mitochondrial
fission
1
protein
(Fis1)
lysine
20
(Fis1
K20la).
Fis1
K20la
promoted
excessive
subsequently
induced
ATP
depletion,
reactive
oxygen
species
(mtROS)
overproduction,
apoptosis.
In
contrast,
PDHA1
activation
sodium
dichloroacetate
(DCA)
or
SIRT3
overexpression
decreased
levels
K20la,
thereby
alleviating
conclusion,
our
results
show
enhance
which
mediates
exacerbates
Reducing
attenuate
Phytotherapy Research,
Год журнала:
2024,
Номер
38(5), С. 2496 - 2517
Опубликована: Март 6, 2024
Abstract
We
investigated
the
mechanism
by
which
quercetin
preserves
mitochondrial
quality
control
(MQC)
in
cardiomyocytes
subjected
to
ischemia–reperfusion
stress.
An
enzyme‐linked
immunosorbent
assay
was
employed
vivo
experiments
assess
myocardial
injury
markers,
measure
transcript
levels
of
SIRT5/DNAPK‐cs/MLKL
during
various
time
intervals
ischemia–reperfusion,
and
observe
structural
changes
using
transmission
electron
microscopy.
In
vitro
investigations,
adenovirus
transfection
establish
a
gene‐modified
model
DNA‐PKcs,
primary
were
obtained
from
mouse
with
modified
SIRT5
gene.
Reverse
transcription
polymerase
chain
reaction,
laser
confocal
microscopy,
immunofluorescence
localization,
JC‐1
fluorescence
assay,
Seahorse
energy
analysis,
other
assays
applied
corroborate
regulatory
influence
on
MQC
network
after
ischemia–reperfusion.
demonstrated
that
caused
structure
myocardium.
It
seen
had
beneficial
effect
tissue,
providing
protection.
As
process
continued,
DNA‐PKcs/SIRT5/MLKL
transcripts
also
found
change.
investigations
revealed
mitigated
cardiomyocyte
oxidative
stress
through
regulated
mitophagy
kinetics
sustain
optimal
metabolism
levels.
Quercetin,
desuccinylation,
modulated
stability
together
they
“mitophagy‐unfolded
protein
response.”
This
preserved
integrity
membrane
genome,
dynamics,
metabolism.
Quercetin
may
operate
synergistically
oversee
regulation
unfolded
response
DNA‐PKcs‐SIRT5
interaction.
International Journal of Biological Sciences,
Год журнала:
2024,
Номер
20(11), С. 4458 - 4475
Опубликована: Янв. 1, 2024
This
study
investigated
the
mechanism
by
which
NR4A1
regulates
mitochondrial
fission
factor
(Mff)-related
and
FUN14
domain
1
(FUNDC1)-mediated
mitophagy
following
cardiac
ischemia-reperfusion
injury(I/R).
Our
findings
showed
that
damage
regulation
was
positively
correlated
with
pathological
pan-apoptosis
of
myocardial
cell
mitochondria.
Compared
wild-type
mice
(WT),
NR4A1-knockout
exhibited
resistance
to
injury
fission,
characterized
activation.
Results
increased
expression
level,
activating
mediated
Mff
restoring
phenotype
FUNDC1.
The
inactivation
FUNDC1
phosphorylation
could
not
mediate
normalization
in
a
timely
manner,
leading
an
excessive
stress
response
unfolded
proteins
imbalance
homeostasis.
process
disrupted
quality
control
network,
accumulation
damaged
mitochondria
activation
pan-apoptotic
programs.
data
indicate
is
novel
critical
target
I/R
exertsand
negative
regulatory
effects
Mff-mediated
mito-fission
inhibiting
FUNDC1-mediated
mitophagy.
Targeting
crosstalk
balance
between
NR4A1-Mff-FUNDC1
potential
approach
for
treating
I/R.
International Immunopharmacology,
Год журнала:
2023,
Номер
115, С. 109716 - 109716
Опубликована: Янв. 16, 2023
Sepsis-induced
cardiomyopathy
(SIC)
is
the
main
complication
and
a
leading
cause
of
death
in
intensive
care
units.
S100a8/a9
calcium-binding
protein
that
participates
various
inflammatory
diseases;
however,
its
role
sepsis-induced
underlying
mechanism
remains
to
be
explored.
Here,
septic
was
induced
with
cecal
ligation
puncture
(CLP)
S100a9-knockout
(KO)
mice
lacking
heterodimer
or
wild-type
(WT)
administered
an
S100a9-specific
inhibitor
Paquinimod
(Paq),
which
prevents
binding
S100a9
toTLR4.
Our
results
showed
expression
heart
peaked
24
h
following
CLP
operation,
declined
at
48
returned
baseline
72
h.
Loss
by
knockout
protected
against
CLP-induced
mortality,
cardiac
dysfunction,
myocyte
apoptosis,
recruitment
Mac-2+
macrophages,
superoxide
production,
pro-inflammatory
cytokines
genes
compared
WT
mice.
Moreover,
S100a9-KO
significantly
attenuated
activation
ERK1/2-Drp1
(S616)
pathway,
excessive
mitochondrial
fission,
respiration
dysfunction.
In
contrast,
ERK1/2
agonist
tBHQ
reversed
inhibitory
effects
on
Finally,
administration
Paq
markedly
prevented
fission
dysfunction
vehicle
control.
summary,
our
data
reveal,
for
first
time,
plays
critical
mediating
SIC,
presumably
activating
TLR4-ERK1/2-Drp1-dependent
highlight
blockage
may
promising
therapeutic
strategy
prevent
SIC
patients
sepsis.
