BMC Cardiovascular Disorders,
Год журнала:
2024,
Номер
24(1)
Опубликована: Ноя. 16, 2024
Myocardial
ischemia-reperfusion
(I/R)
injury
caused
by
revascularization
treatment
is
the
leading
cause
of
cardiac
damage
aggravation
in
ischemic
heart
disease.
Increasing
evidence
has
unraveled
crucial
role
pyroptosis
myocardial
I/R
injury.
Of
note,
lactylation
been
validated
to
be
participated
modulating
pyroptosis.
Hence,
this
study
was
aimed
elaborate
potential
and
mechanism
damage.
We
established
cell
model
through
inducing
hypoxia/reoxygenation
(H/R)
H9c2
cells.
It
uncovered
that
H/R
stimulation
drove
cardiomyocyte
upregulated
total
level.
Further,
we
demonstrated
promoting
contributed
H/R-evoked
pyroptosis,
whereas
silencing
LDHA
led
opposite
results.
More
than
that,
confirmed
facilitate
NLRP3
at
K245
site
increase
its
protein
stability.
Our
findings
indicated
activation
abolished
function
deficiency
H/R-treated
In
concert
with
aforementioned
outcomes,
knockout
attenuated
infarct
size
mice
upregulation
counteracted
effects
on
I/R-evoked
vivo.
To
summarize,
current
research
provided
persuasive
promoted
via
enhancing
induce
Journal of Translational Medicine,
Год журнала:
2024,
Номер
22(1)
Опубликована: Янв. 10, 2024
As
more
is
learned
about
lactate,
it
acts
as
both
a
product
and
substrate
functions
shuttle
system
between
different
cell
populations
to
provide
the
energy
for
sustaining
tumor
growth
proliferation.
Recent
discoveries
of
protein
lactylation
modification
mediated
by
lactate
play
an
increasingly
significant
role
in
human
health
(e.g.,
neural
osteogenic
differentiation
maturation)
diseases
tumors,
fibrosis
inflammation,
etc.).
These
views
are
critically
first
described
detail
this
review.
Hence,
here,
we
focused
on
new
target,
lactylation,
which
may
be
"double-edged
sword"
diseases.
The
main
purpose
review
was
describe
how
multiple
physiological
pathological
processes
their
potential
mechanisms
through
in-depth
summary
preclinical
vitro
vivo
studies.
Our
work
aims
ideas
treating
accelerate
translation
from
bench
bedside.
Theranostics,
Год журнала:
2024,
Номер
14(11), С. 4297 - 4317
Опубликована: Янв. 1, 2024
Aim:Although
lactate
supplementation
at
the
reperfusion
stage
of
ischemic
stroke
has
been
shown
to
offer
neuroprotection,
whether
role
accumulated
ischemia
phase
is
neuroprotection
or
not
remains
largely
unknown.Thus,
in
this
study,
we
aimed
investigate
roles
and
mechanisms
brain
regulating
injury
stroke.Methods
Results:
Pharmacological
inhibition
production
by
either
inhibiting
LDHA
glycolysis
markedly
attenuated
mouse
stroke.In
contrast,
additional
supplement
further
aggravates
injury,
which
may
be
closely
related
induction
neuronal
death
A1
astrocytes.The
contributing
increased
promotive
formation
protein
lysine
lactylation
(Kla),
while
post-treatment
did
influence
Kla
levels
with
neuroprotection.Increased
were
found
mainly
neurons
HPLC-MS/MS
analysis
immunofluorescent
staining.Then,
pharmacological
blocking
shuttle
showed
decreased
brains.Additionally,
Ldha
specific
knockout
astrocytes
(Aldh1l1
CreERT2
;
fl/fl
mice,
cKO)
mice
MCAO
constructed
results
that
level
was
accompanied
a
decrease
volume
cerebral
infarction
cKO
compared
control
groups.Furthermore,
writer
p300
its
antagonist
A-485
significantly
alleviates
glial
activation
reduction
level,
resulting
extending
window
improving
functional
recovery
for
stroke.Conclusion:
Collectively,
derived
from
promoting
formation,
suggesting
presents
new
therapeutic
targets
treatment
stroke.
Frontiers in Immunology,
Год журнала:
2024,
Номер
14
Опубликована: Янв. 9, 2024
Osteoarthritis
(OA)
has
been
a
leading
cause
of
disability
in
the
elderly
and
there
remains
lack
effective
therapeutic
approaches
as
mechanisms
pathogenesis
progression
have
yet
to
be
elucidated.
As
OA
progresses,
cellular
metabolic
profiles
energy
production
are
altered,
emerging
reprogramming
highlights
importance
specific
pathways
disease
progression.
crucial
part
glucose
metabolism,
glycolysis
bridges
inflammatory
dysfunctions.
Moreover,
glycolytic
pathway
is
involved
different
areas
metabolism
inflammation,
associated
with
variety
transcription
factors.
To
date,
it
not
fully
elucidated
whether
changes
its
key
enzymes
onset
or
OA.
This
review
summarizes
important
role
mediating
inducing
tissue
inflammation
injury,
aim
providing
further
insights
into
pathological
functions
proposing
new
targets
for
treatment
Biological reviews/Biological reviews of the Cambridge Philosophical Society,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 16, 2024
ABSTRACT
In
recent
years,
a
significant
breakthrough
has
emerged
in
biology,
the
identification
of
lactylation,
novel
post‐translational
process.
This
intriguing
modification
is
not
limited
to
specific
class
proteins
but
occurs
across
diverse
range,
including
histones,
signalling
molecules,
enzymes,
and
substrates.
It
can
exert
broad
regulatory
role
various
diseases,
ranging
from
developmental
anomalies
neurodegenerative
disorders
inflammation
cancer.
Thus,
it
presents
exciting
opportunities
for
exploring
innovative
treatment
approaches.
As
result,
there
been
surge
research
interest,
leading
deeper
understanding
molecular
mechanisms
functions
underlying
lactylation
within
physiological
pathological
processes.
Here,
we
review
detection
biological
disease
effects,
providing
systematic
overview
this
modification.
Communications Biology,
Год журнала:
2024,
Номер
7(1)
Опубликована: Дек. 26, 2024
Acute
ischemic
stroke
(AIS)
triggers
immune
responses
and
neuroinflammation,
contributing
to
brain
injury.
Histone
lactylation,
a
metabolic
stress-related
histone
modification,
plays
critical
role
in
various
diseases,
but
its
involvement
cerebral
ischemia
remains
unclear.
This
study
utilized
transient
middle
artery
occlusion/reperfusion
(MCAO/R)
model
an
oxygen–glucose
deprivation/reoxygenation
(OGD/R)
investigate
the
of
microglial
lactylation
ischemia–reperfusion
Lactate
overload
post-AIS
increased
while
reduced
SMEK1
expression
microglia
correlated
with
elevated
lactate
neuroinflammation.
Microglia-specific
deficiency
enhanced
production
by
inhibiting
pyruvate
dehydrogenase
kinase
3-pyruvate
(PDK3-PDH)
pathway,
increasing
H3
lysine
9
(H3K9la),
activating
Ldha
Hif-1α
transcription,
promoting
glycolysis.
overexpression
improved
neurological
recovery
mice.
highlights
as
novel
regulator
potential
therapeutic
target
for
mitigating
neuroinflammation
enhancing
after
AIS.
identifies
Journal of Neuroinflammation,
Год журнала:
2025,
Номер
22(1)
Опубликована: Март 12, 2025
Histone
lactylation,
a
newly
glycosis-related
histone
modification,
plays
crucial
role
in
the
regulation
of
gene
expression
various
immune
cells.
However,
lactylation
astrocytes
remains
unclear.
Here,
this
study
showed
that
H3K18
(H3K18la)
levels
were
upregulated
primary
under
unconjugated
bilirubin
(UCB)
stimulation
and
hippocampus
encephalopathy
(BE)
rats.
Inhibition
glycolysis
decreased
H3K18la
attenuated
pyroptosis
both
vitro
vivo.
CUT&
Tag
RNA-seq
results
revealed
was
enriched
at
promoter
nucleotide-binding
oligomerization
domain
2
(NOD2)
promoted
its
transcription.
Moreover,
NOD2
boosted
activation
downstream
mitogen-activated
protein
kinase
(MAPK)
nuclear
factor-kappa
B
(NF-κB)
signaling
pathways,
which
exacerbated
neuroinflammation
BE.
Collectively,
provides
novel
understanding
epigenetic
astrocytes,
interruption
H3K18la/NOD2
axis
may
represent
therapeutic
strategy
for
treating
encephalopathy.
