Redox Biology,
Год журнала:
2023,
Номер
63, С. 102760 - 102760
Опубликована: Май 23, 2023
Cancer
cells
and
ischemic
diseases
exhibit
unique
metabolic
responses
adaptations
to
energy
stress.
Forkhead
box
O
3a
(FoxO3a)
is
a
transcription
factor
that
plays
an
important
role
in
cell
metabolism,
mitochondrial
dysfunction
oxidative
stress
response.
Although
the
AMP-activated
protein
kinase
(AMPK)/FoxO3a
signaling
pathway
pivotal
maintaining
homeostasis
under
conditions
of
stress,
AMPK/FoxO3a
mitochondria-associated
ferroptosis
has
not
yet
been
fully
elucidated.
We
show
glucose
starvation
induced
activation
inhibited
by
erastin.
Inhibition
AMPK
or
loss
FoxO3a
cancer
condition
can
sensitize
these
ferroptosis.
Glucose
deprivation
mitochondria-related
gene
expression,
reduced
DNA(mtDNA)
copy
number,
decreased
expression
proteins
lowered
levels
respiratory
complexes
inducing
FoxO3a.
Loss
promoted
membrane
potential
hyperpolarization,
oxygen
consumption,
lipid
peroxide
accumulation
abolished
protective
effects
on
vitro.
In
addition,
we
identified
FDA-approved
antipsychotic
agent,
potent
agonist
trifluoperazine,
which
largely
ferroptosis-associated
cerebral
ischemia-reperfusion
(CIR)
injuries
rats
through
AMPK/FoxO3a/HIF-1α
mitochondria-dependent
mechanisms.
found
binds
promoters
SLC7A11
reduces
CIR-mediated
glutamate
excitotoxicity
inhibiting
SLC7A11.
Collectively,
results
suggest
modulation
regulates
activity
alters
The
regulation
may
play
crucial
controls
balance
confers
resistance
CIR
injuries.
Frontiers in Pharmacology,
Год журнала:
2022,
Номер
12
Опубликована: Фев. 22, 2022
Doxorubicin
(DOX)
is
an
anthracycline
antibiotic
that
used
extensively
for
the
management
of
carcinoma;
however,
its
clinical
application
limited
due
to
serious
cardiotoxic
side
effects.
Ferroptosis
represents
iron-dependent
and
reactive
oxygen
species
(ROS)-related
cell
death
has
been
proven
contribute
progression
DOX-induced
cardiomyopathy.
Fisetin
a
natural
flavonoid
abundantly
present
in
fruits
vegetables.
It
reported
exert
cardioprotective
effects
against
cardiotoxicity
experimental
rats.
However,
underlying
mechanisms
remain
unknown.
The
study
investigated
role
fisetin
molecular
mechanism
through
experiments
cardiomyopathy
rat
H9c2
models.
results
revealed
treatment
could
markedly
abate
by
alleviating
cardiac
dysfunction,
ameliorating
myocardial
fibrosis,
mitigating
hypertrophy
rats,
attenuating
ferroptosis
cardiomyocytes
reversing
decline
GPX4
level.
Mechanistically,
exerted
antioxidant
effect
reducing
MDA
lipid
ROS
levels
increasing
glutathione
(GSH)
Moreover,
protective
SIRT1
expression
Nrf2
mRNA
protein
nuclear
translocation,
which
resulted
activation
downstream
genes
such
as
HO-1
FTH1.
Selective
inhibition
attenuated
cells,
turn
decreased
GSH
levels,
well
Nrf2,
HO-1,
FTH1
expressions.
In
conclusion,
exerts
therapeutic
inhibiting
via
SIRT1/Nrf2
signaling
pathway
activation.
Cell Death and Disease,
Год журнала:
2021,
Номер
12(11)
Опубликована: Окт. 29, 2021
Abstract
Acute
lung
injury
(ALI)
carries
a
mortality
rate
of
~50%
and
is
hot
topic
in
the
world
critical
illness
research.
Nuclear
factor
erythroid
2-related
2
(Nrf2)
modulator
intracellular
oxidative
homeostasis
serves
as
an
antioxidant.
The
Nrf2-related
anti-oxidative
stress
strongly
associated
with
ferroptosis
suppression.
Meanwhile,
telomerase
reverse
transcriptase
(TERT),
catalytic
portion
protein,
reported
to
travel
mitochondria
alleviate
ROS.
In
our
study,
we
found
that
TERT
was
significantly
reduced
tissue
Nrf2
−/−
mice
model
intestinal
ischemia/reperfusion-induced
acute
(IIR-ALI).
addition,
MDA
levels
showed
marked
increase,
whereas
GSH
GPX4
fell
drastically
ALI
models.
Moreover,
typical-related
structural
changes
were
observed
type
II
alveolar
epithelial
cells
IIR
model.
We
further
employed
scanning
transmission
X-ray
microscopy
(STXM)
examine
Fe
distribution
within
cells.
Based
on
observations,
massive
aggregates
MLE-12
upon
OGD/R
(oxygen
glucose
deprivation/reperfusion)
induction.
Additionally,
silencing
dramatically
SLC7A11
levels,
exacerbated
cellular
injuries.
contrast,
TERT-overexpressing
exhibited
elevation
thereby
inhibited
ferroptosis.
Collectively,
these
data
suggest
can
negatively
regulate
via
modulation
levels.
conclusion
from
this
study
brings
insight
into
new
candidates
be
targeted
future
IIR-ALI
therapy.
Annals of Translational Medicine,
Год журнала:
2022,
Номер
10(6), С. 368 - 368
Опубликована: Март 1, 2022
Background
and
Objective:
Ferroptosis
is
a
recently
discovered
form
of
cell
death
which
differs
from
other
forms
in
terms
morphology,
biochemistry,
regulatory
mechanisms.
regulated
by
complex
system
the
precise
molecular
mechanisms
are
still
being
elucidated.
Over
past
few
years,
extensive
research
has
revealed
that
essence
ferroptosis
iron-dependent
accumulation
lipid
hydroperoxides
induced
oxidative
stress,
System
Xc-glutathione
(GSH)-glutathione
peroxidase
4
(GPX4)
pathway
main
prevention
system.
Meanwhile,
antioxidant
systems
have
also
been
implicated
regulating
ferroptosis,
including
transsulfuration
pathway,
mevalonate
inhibitory
protein
1
(FSP1)-Coenzyme
Q10
(CoQ10)
dihydroorotate
dehydrogenase
(DHODH)-dihydroubiquione
(CoQH2)
GTP
cyclohydrolase-1
(GCH1)-tetrahydrobiopterin
(BH4)
pathway.
This
article
reviews
its
critical
role
systems,
aiming
to
reveal
antioxidation
an
important
method
inhibiting
provide
new
direction
for
treatment
ferroptosis-related
diseases.
Methods:
We
searched
all
original
papers
about
using
PubMed
November
2021.
The
search
used
included:
‘ferroptosis’,
‘ferroptosis
inducers’,
inhibitors’,
GSH’,
GPX4’,
Xc-’,
‘SLC7A11’,
‘P53’,
‘NRF2
ferroptosis’,
‘iron
metabolism’,
‘lipid
peroxidation’,
‘antioxidant
systems’,
‘transsulfuration
pathway’,
‘mevalonate
‘FSP1-CoQ10’,
‘DHODH-CoQH2’,
‘GCH1-BH4’.
Key
Content
Findings:
first
introduced
origin
common
inhibitors
inducers.
Next,
we
discussed
existing
studies.
Finally,
briefly
summarized
relationship
between
It
reveals
ferroptosis.
Conclusions:
review
discusses
recent
rapid
progress
understanding
several
systems.
Nanoscale,
Год журнала:
2021,
Номер
13(4), С. 2266 - 2285
Опубликована: Янв. 1, 2021
Although
ferroptosis
is
an
iron-dependent
cell
death
mechanism
involved
in
the
development
of
some
severe
diseases
(e.g.,
Parkinsonian
syndrome,
stroke
and
tumours),
combination
nanotechnology
with
for
treatment
these
has
attracted
substantial
research
interest.
However,
it
challenging
to
differentiate
nanoparticle-induced
from
other
types
deaths
apoptosis,
pyroptosis,
necrosis),
elucidate
detailed
mechanisms
identify
key
property
nanoparticles
responsible
ferroptotic
deaths.
Therefore,
a
summary
aspects
current
on
nano-ferroptosis
important
timely.
In
this
review,
we
endeavour
summarize
convincing
techniques
that
can
be
employed
specifically
examine
Then,
discuss
molecular
initiating
events
nanosized
inducers
cascade
signals
cells,
therefore
elaborate
mechanisms.
Besides,
physicochemical
properties
nano-inducers
are
also
discussed
acquire
fundamental
understanding
nano-structure-activity
relationships
(nano-SARs)
ferroptosis,
which
may
facilitate
design
nanomaterials
deliberately
tune
ferroptosis.
Finally,
future
perspectives
its
applications
provided.
Bioengineered,
Год журнала:
2021,
Номер
12(1), С. 5279 - 5288
Опубликована: Янв. 1, 2021
Asthma
occurs
accompanied
by
the
ferroptosis
in
bronchial
epithelial
cells,
during
which
Interleukin-6
(IL-6)
plays
a
key
role.
However,
associations
between
IL-6,
and
asthma
have
not
been
reported.
Bronchial
cells
BEAS-2B
were
induced
different
concentrations
of
IL-6
cell
viability
was
detected
MTT
assay.
The
TBARS
production
rate
corresponding
kit.
expression
oxidative
stress-related
indexes
ELISA.
Iron
Assay
Kits
total
iron
levels
ferrous
ion
(Fe2+)
levels.
Labile
pool
assay
used
to
detect
unstable
pool.
ferroptosis-related
proteins
Western
blot.
To
further
examine
mechanism
action,
inhibitor
Ferrostatin
1
(Fer-1),
antioxidant
NAC,
supplement
Fe
added.
We
found
that
decreased
activity,
promoted
lipid
peroxidation,
disrupted
homeostasis
death
cells.
pretreatment
with
Ferrostatin-1
(Fer-1)
NAC
partially
reversed
effect
on
peroxidation
while
augmented
effect.
Overall,
promotes
inducing
reactive
oxygen
species
(ROS)-dependent
disrupting
homeostasis.
FEBS Journal,
Год журнала:
2022,
Номер
290(7), С. 1688 - 1704
Опубликована: Фев. 2, 2022
Ferroptosis
is
triggered
by
a
chain
of
intracellular
labile
iron-dependent
peroxidation
cell
membrane
phospholipids.
important
not
only
as
cause
ischaemic
and
neurodegenerative
diseases
but
also
mechanism
cancer
suppression,
better
understanding
its
regulatory
required.
It
has
become
clear
that
ferroptosis
finely
controlled
two
oxidative
stress-responsive
transcription
factors,
NRF2
(NF-E2-related
factor
2)
BACH1
(BTB
CNC
homology
1).
inhibit
promote
ferroptosis,
respectively,
activating
or
suppressing
the
expression
genes
in
major
pathways
ferroptosis:
iron
metabolism,
GSH
(glutathione)
-GPX4
(glutathione
peroxidase
4)
pathway
FSP1
(ferroptosis
suppressor
protein
1)-CoQ
(coenzyme
Q)
pathway.
In
addition
to
this,
control
through
regulation
lipid
metabolism
differentiation.
This
multifaceted
considered
have
been
acquired
during
evolution
multicellular
organisms,
allowing
utilization
for
maintaining
homeostasis,
including
suppression.
terms
cell-cell
interaction,
it
revealed
property
propagating
surrounding
cells
along
with
peroxidation.
The
propagation
phenomenon
could
be
used
realize
anticancer
therapy
future.
this
review,
these
points
will
summarized
discussed.
Cellular & Molecular Biology Letters,
Год журнала:
2022,
Номер
27(1)
Опубликована: Март 19, 2022
Acute
lung
injury
(ALI)
has
received
considerable
attention
in
the
field
of
intensive
care
as
it
is
associated
with
a
high
mortality
rate.
Obacunone
(OB),
widely
found
citrus
fruits,
natural
bioactive
compound
anti-inflammatory
and
antioxidant
activities.
However,
not
clear
whether
OB
protects
against
lipopolysaccharide
(LPS)-induced
ALI.
Therefore,
this
study,
we
aimed
to
evaluate
protective
effects
potential
mechanisms
LPS-induced
ALI
BEAS-2B
cell
injury.We
established
model
mouse
by
treating
LPS.
Samples
vitro
were
subjected
death,
Cell
Counting
Kit-8,
lactate
dehydrogenase
(LDH)
release
assays.
The
total
number
cells
neutrophils,
protein
content,
levels
IL-6,
TNF-α,
IL-1β
determined
bronchoalveolar
lavage
fluid
(BALF).
Glutathione,
reactive
oxygen
species,
malondialdehyde
tissue.
Additionally,
immunohistochemical
analysis,
immunofluorescence,
western
blot,
quantitative
real-time
PCR,
enzyme-linked
immunosorbent
assay
conducted
examine
OB.
Furthermore,
mice
treated
an
Nrf2
inhibitor
(ML385)
verify
its
role
ferroptosis.
Data
analyzed
using
one-way
analysis
variance
or
paired
t-tests.Compared
LPS
group,
effectively
alleviated
decreasing
wet/dry
weight
ratio,
species
production,
superoxide
dismutase
glutathione
consumption
vivo.
In
addition,
significantly
histopathological
injury,
reduced
inflammatory
cytokine
secretion
Fe2+
4-HNE
levels,
upregulated
GPX4,
SLC7A11,
expression.
Mechanistically,
activated
inhibiting
ubiquitinated
proteasome
degradation.
ML385
reversed
ALI.Overall,
alleviates
ALI,
making
novel
agent
