The FASEB Journal,
Journal Year:
2024,
Volume and Issue:
38(15)
Published: Aug. 2, 2024
Abstract
Atherosclerosis
is
a
leading
cause
of
cardiovascular
diseases
(CVDs),
often
resulting
in
major
adverse
events
(MACEs),
such
as
myocardial
infarction
and
stroke
due
to
the
rupture
or
erosion
vulnerable
plaques.
Ferroptosis,
an
iron‐dependent
form
cell
death,
has
been
implicated
development
atherosclerosis.
Despite
its
involvement
CVDs,
specific
role
ferroptosis
atherosclerotic
plaque
stability
remains
unclear.
In
this
study,
we
confirmed
presence
unstable
plaques
demonstrated
that
inhibitor
ferrostatin‐1
(Fer‐1)
stabilizes
apolipoprotein
E
knockout
(
Apoe
−/−
)
mice.
Using
bioinformatic
analysis
combining
RNA
sequencing
(RNA‐seq)
with
single‐cell
(scRNA‐seq),
identified
Yes‐associated
protein
1
(YAP1)
potential
key
regulator
vascular
smooth
muscle
cells
(VSMCs)
vitro,
found
YAP1
protects
against
oxidized
low‐density
lipoprotein
(oxLDL)‐induced
VSMCs.
Mechanistically,
exerts
anti‐ferroptosis
effects
by
regulating
expression
glutaminase
(GLS1)
promote
synthesis
glutamate
(Glu)
glutathione
(GSH).
These
findings
establish
novel
mechanism
where
inhibition
promotes
stabilization
through
YAP1/GLS1
axis,
attenuating
VSMC
ferroptosis.
Thus,
targeting
axis
suppress
may
represent
strategy
for
preventing
treating
Signal Transduction and Targeted Therapy,
Journal Year:
2023,
Volume and Issue:
8(1)
Published: Dec. 10, 2023
Abstract
Ferroptosis,
a
unique
modality
of
cell
death
with
mechanistic
and
morphological
differences
from
other
modes,
plays
pivotal
role
in
regulating
tumorigenesis
offers
new
opportunity
for
modulating
anticancer
drug
resistance.
Aberrant
epigenetic
modifications
posttranslational
(PTMs)
promote
resistance,
cancer
progression,
metastasis.
Accumulating
studies
indicate
that
can
transcriptionally
translationally
determine
vulnerability
to
ferroptosis
functions
as
driver
nervous
system
diseases
(NSDs),
cardiovascular
(CVDs),
liver
diseases,
lung
kidney
diseases.
In
this
review,
we
first
summarize
the
core
molecular
mechanisms
ferroptosis.
Then,
roles
processes,
including
histone
PTMs,
DNA
methylation,
noncoding
RNA
regulation
such
phosphorylation,
ubiquitination,
SUMOylation,
acetylation,
ADP-ribosylation,
are
concisely
discussed.
The
PTMs
genesis
cancers,
NSD,
CVDs,
well
application
PTM
modulators
therapy
these
then
discussed
detail.
Elucidating
mediated
by
will
facilitate
development
promising
combination
therapeutic
regimens
containing
or
PTM-targeting
agents
inducers
be
used
overcome
chemotherapeutic
resistance
could
prevent
addition,
highlight
potential
approaches
chemoresistance
halt
Autophagy,
Journal Year:
2024,
Volume and Issue:
20(6), P. 1213 - 1246
Published: March 6, 2024
Macroautophagy/autophagy
is
a
complex
degradation
process
with
dual
role
in
cell
death
that
influenced
by
the
types
are
involved
and
stressors
they
exposed
to.
Ferroptosis
an
iron-dependent
oxidative
form
of
characterized
unrestricted
lipid
peroxidation
context
heterogeneous
plastic
mechanisms.
Recent
studies
have
shed
light
on
involvement
specific
autophagy
(e.g.
ferritinophagy,
lipophagy,
clockophagy)
initiating
or
executing
ferroptotic
through
selective
anti-injury
proteins
organelles.
Conversely,
other
forms
reticulophagy
lysophagy)
enhance
cellular
defense
against
damage.
Dysregulated
autophagy-dependent
ferroptosis
has
implications
for
diverse
range
pathological
conditions.
This
review
aims
to
present
updated
definition
ferroptosis,
discuss
influential
substrates
receptors,
outline
experimental
methods,
propose
guidelines
interpreting
results.
International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(6), P. 5093 - 5093
Published: March 7, 2023
Uridine
metabolism
is
extensively
reported
to
be
involved
in
combating
oxidative
stress.
Redox-imbalance-mediated
ferroptosis
plays
a
pivotal
role
sepsis-induced
acute
lung
injury
(ALI).
This
study
aims
explore
the
of
uridine
ALI
and
regulatory
mechanism
ferroptosis.
The
Gene
Expression
Omnibus
(GEO)
datasets
including
tissues
lipopolysaccharides
(LPS)
-induced
model
or
human
blood
sample
sepsis
were
collected.
In
vivo
vitro,
LPS
was
injected
into
mice
administered
THP-1
cells
generate
inflammatory
models.
We
identified
that
phosphorylase
1
(UPP1)
upregulated
septic
samples
significantly
alleviated
injury,
inflammation,
tissue
iron
level
lipid
peroxidation.
Nonetheless,
expression
biomarkers,
SLC7A11,
GPX4
HO-1,
upregulated,
while
synthesis
gene
(ACSL4)
greatly
restricted
by
supplementation.
Moreover,
pretreatment
inducer
(Erastin
Era)
weakened
inhibitor
(Ferrostatin-1
Fer-1)
strengthened
protective
effects
uridine.
Mechanistically,
inhibited
macrophage
activating
Nrf2
signaling
pathway.
conclusion,
dysregulation
novel
accelerator
for
supplementation
may
offer
potential
avenue
ameliorating
suppressing
Redox Biology,
Journal Year:
2024,
Volume and Issue:
74, P. 103194 - 103194
Published: May 16, 2024
Elevated
lactate
levels
are
a
significant
biomarker
of
sepsis
and
positively
associated
with
sepsis-related
mortality.
Sepsis-associated
lung
injury
(ALI)
is
leading
cause
poor
prognosis
in
clinical
patients.
However,
the
underlying
mechanisms
lactate's
involvement
sepsis-associated
ALI
remain
unclear.
In
this
study,
we
demonstrate
that
regulates
N6-methyladenosine
(m6A)
modification
by
facilitating
p300-mediated
H3K18la
binding
to
METTL3
promoter
site.
The
METTL3-mediated
m6A
enriched
ACSL4,
its
mRNA
stability
regulated
through
YTHDC1-dependent
pathway.
Furthermore,
short-term
stimulation
upregulates
which
promotes
mitochondria-associated
ferroptosis.
Inhibition
knockdown
or
targeted
inhibition
effectively
suppresses
septic
hyper-lactate-induced
ferroptosis
alveolar
epithelial
cells
mitigates
mice.
Our
findings
suggest
induces
via
GPR81/H3K18la/METTL3/ACSL4
axis
during
ALI.
These
results
reveal
histone
lactylation-driven
mechanism
inducing
modification.
Targeting
represents
promising
therapeutic
strategy
for
patients
Molecular Cancer,
Journal Year:
2025,
Volume and Issue:
24(1)
Published: Jan. 17, 2025
Drug
resistance
is
a
common
challenge
in
clinical
tumor
treatment.
A
reduction
drug
sensitivity
of
cells
often
accompanied
by
an
increase
autophagy
levels,
leading
to
autophagy-related
resistance.
The
effectiveness
combining
chemotherapy
drugs
with
inducers/inhibitors
has
been
widely
confirmed,
but
the
mechanisms
are
still
unclear.
Ferroptosis
and
pyroptosis
can
be
affected
various
types
autophagy.
Therefore,
ferroptosis
have
crosstalk
via
autophagy,
potentially
switch
cell
death
under
certain
conditions.
As
two
forms
inflammatory
programmed
death,
different
effects
on
inflammation,
cGAS-STING
signaling
pathway
also
involved.
it
plays
important
role
progression
some
chronic
diseases.
This
review
discusses
relationship
between
pyroptosis,
attempts
uncover
reasons
behind
evasion
nature
MedComm,
Journal Year:
2025,
Volume and Issue:
6(3)
Published: Feb. 23, 2025
Ferroptosis
is
a
distinct
form
of
iron-dependent
programmed
cell
death
characterized
primarily
by
intracellular
iron
accumulation
and
lipid
peroxidation.
Multiple
cellular
processes,
including
amino
acid
metabolism,
various
signaling
pathways,
autophagy,
have
been
demonstrated
to
influence
the
induction
progression
ferroptosis.
Recent
investigations
elucidated
that
ferroptosis
plays
crucial
role
in
pathogenesis
pulmonary
disorders,
lung
injury,
chronic
obstructive
disease,
fibrosis,
asthma.
increasingly
recognized
as
promising
novel
strategy
for
cancer
treatment.
Various
immune
cells
within
tumor
microenvironment,
CD8+
T
cells,
macrophages,
regulatory
natural
killer
dendritic
shown
induce
modulate
process
through
regulation
metabolism
pathways.
Conversely,
can
reciprocally
alter
metabolic
environment,
leading
activation
or
inhibition
functions,
thereby
modulating
responses.
This
paper
reviews
molecular
mechanism
describes
discusses
connection
between
microenvironment
diseases,
development
prospect
their
interaction
treatment
diseases.
Chinese Medicine,
Journal Year:
2025,
Volume and Issue:
20(1)
Published: Jan. 15, 2025
Abstract
Background
Sepsis-induced
acute
lung
injury
(ALI)
is
a
severe
clinical
condition
accompanied
with
high
mortality.
Tangeretin,
which
widely
found
in
citrus
fruits,
has
been
reported
to
exert
antioxidant
and
anti-inflammatory
properties.
However,
whether
tangeretin
protects
against
sepsis-induced
ALI
the
potential
mechanisms
remain
unclear.
Methods
We
established
an
model
via
intraperitoneally
injected
5
mg/kg
lipopolysaccharides
(LPS)
for
12
h.
Tangeretin
was
applied
30
min
before
LPS
treatment.
Dexamethasone
(Dex)
used
as
positive
control.
Hematoxylin
eosin
(HE)
staining
protein
content
bronchoalveolar
lavage
fluid
(BALF)
were
determined
detect
degree
of
injury.
RNA-seq
also
explore
effect
on
ALI.
In
vitro,
RAW264.7
treated
Nrf2
siRNA,
expression
ferroptosis-associated
biomarkers,
including
glutathione
peroxidase
4
(GPX4)
prostaglandin-endoperoxide
synthase
2
(PTGS2)
assessed.
Glutathione
(GSH),
malondialdehyde
(MDA)
levels,
reactive
oxygen
species
(ROS)
inflammatory
factors
both
vivo
vitro.
Furthermore,
mice
inhibitor
(ML385)
verify
mechanism
inhibiting
ferroptosis.
Data
analyzed
using
one
way
analysis
variance
or
two-tailed
unpaired
t
tests.
Results
Our
study
demonstrated
that
significantly
alleviated
injury,
reversed
LPS-induced
reduction
GPX4
GSH,
mitigates
elevation
PTGS2
MDA
levels.
reduced
4-HNE
iron
Besides,
levels
LPS-stimulated
IL-6,
IL-1β
TNF-α
decreased
by
tangeretin.
bioinformatics
inhibited
response.
Mechanistically,
we
identified
GPX4-dependent
lipid
peroxidation
through
activation
Nrf2.
The
silence
abolished
inhibitory
oxidative
stress,
response
ferroptosis
cells.
Additionally,
all
protective
effects
inhibitor-treated
mice.
Conclusion
critical
contributing
promising
therapeutic
candidate,
effectively
upregulating
signaling
pathway.
BMC Biology,
Journal Year:
2025,
Volume and Issue:
23(1)
Published: Feb. 4, 2025
Lung
ischemia–reperfusion
(I/R)
injury
is
a
common
clinical
pathology
associated
with
high
mortality.
The
pathophysiology
of
lung
I/R
involves
ferroptosis
and
elevated
protein
O-GlcNAcylation
levels,
while
the
effect
on
remains
unclear.
This
research
aimed
to
explore
reducing
in
pulmonary
epithelial
cells
caused
by
I/R.
First,
we
identified
O-GlcNAc
transferase
1
(Ogt1)
as
differentially
expressed
gene
acute
injury/acute
respiratory
distress
syndrome
(ALI/ARDS)
patients,
using
single-cell
sequencing,
Gene
Ontology
analysis
(GO
analysis)
revealed
enrichment
process.
We
found
time-dependent
dynamic
alteration
during
injury.
Proteomics
proteins
enriched
multiple
redox-related
pathways
based
KEGG
annotation.
Thus,
generated
Ogt1-conditional
knockout
mice
that
Ogt1
deficiency
aggravated
ferroptosis,
evidenced
lipid
reactive
oxygen
species
(lipid
ROS),
malondialdehyde
(MDA),
Fe2+,
well
alterations
critical
expression
glutathione
peroxidase
4
(GPX4)
solute
carrier
family
7
member
11
(SLC7A11).
Consistently,
inhibited
sensitivity
hypoxia/reoxygenation
(H/R)
injury-induced
TC-1
via
O-GlcNAcylated
NF-E2-related
factor-2
(Nrf2).
Furthermore,
both
chromatin
immunoprecipitation
(ChIP)
assay
dual-luciferase
reporter
indicated
Nrf2
could
bind
translation
start
site
(TSS)
glucose-6-phosphate
dehydrogenase
(G6PDH)
promote
its
transcriptional
activity.
As
an
important
rate-limiting
enzyme
pentose
phosphate
pathway
(PPP),
G6PDH
provided
mass
nicotinamide
adenine
dinucleotide
(NADPH)
improve
redox
state
(GSH)
eventually
led
resistance.
Rescue
experiments
proved
knockdown
or
Nrf2-T334A
(O-GlcNAcylation
site)
mutation
abolished
protective
In
summary,
protect
against
Nrf2/G6PDH
pathway.
Our
work
will
provide
new
basis
for
therapeutic
strategies
ischemia–reperfusion-induced
