Cell Death and Disease,
Год журнала:
2022,
Номер
13(5)
Опубликована: Май 18, 2022
The
concept
of
cell
death
has
been
expanded
beyond
apoptosis
and
necrosis
to
additional
forms,
including
necroptosis,
pyroptosis,
autophagy,
ferroptosis.
These
modalities
play
a
critical
role
in
all
aspects
life,
which
are
noteworthy
for
their
diverse
roles
diseases.
Atherosclerosis
(AS)
vascular
calcification
(VC)
major
causes
the
high
morbidity
mortality
cardiovascular
disease.
Despite
considerable
advances
understanding
signaling
pathways
associated
with
AS
VC,
exact
molecular
basis
remains
obscure.
In
article,
we
review
mechanisms
that
mediate
its
implications
VC.
A
better
underlying
VC
may
drive
development
promising
therapeutic
strategies.
Frontiers in Pharmacology,
Год журнала:
2022,
Номер
13
Опубликована: Июнь 28, 2022
Skin
cutaneous
melanoma
(SKCM,
hereafter
referred
to
as
melanoma)
is
the
most
lethal
skin
cancer
with
increasing
incidence.
Regulated
cell
death
plays
an
important
role
in
tumorigenesis
and
serves
target
for
almost
all
treatment
strategies.
Cuproptosis
recently
identified
copper-dependent
regulated
form
that
relies
on
mitochondria
respiration.
However,
its
remains
unknown.
The
correlation
of
cuproptosis-related
genes
tumor
prognosis
far
be
understood,
either.
In
present
study,
we
explored
between
by
accessing
analyzing
a
public
database
found
11
out
12
were
upregulated
tissues
three
(LIPT1,
PDHA1,
SLC31A1)
have
predictive
value
prognosis.
subgroup
patients
higher
gene
expression
showed
longer
overall
survival
than
those
lower
expression.
We
chose
LIPT1
further
exploration.
was
increased
biopsies
independent
favorable
prognostic
indicator
patients.
Moreover,
positively
correlated
PD-L1
negatively
associated
Treg
infiltration.
after
receiving
immunotherapy,
indicating
LIPT1.
Finally,
pan-cancer
analysis
indicated
differentially
expressed
diverse
cancers
compared
normal
multiple
immune
checkpoints,
especially
PD-L1.
It
could
serve
some
types.
conclusion,
our
study
demonstrated
genes,
LIPT1,
melanoma,
revealed
infiltration
thus
providing
new
clues
assessment
immunotherapy
melanoma.
Trends in Pharmacological Sciences,
Год журнала:
2021,
Номер
43(3), С. 206 - 220
Опубликована: Ноя. 27, 2021
Bcl-2-associated
X
protein
(BAX)
is
a
critical
executioner
of
mitochondrial
regulated
cell
death
through
its
lethal
activity
permeabilizing
the
outer
membrane
(MOM).
While
physiological
function
BAX
ensures
tissue
homeostasis,
dysregulation
leads
to
aberrant
death.
Despite
being
promising
therapeutic
target
for
human
diseases,
historically
development
drugs
has
focused
on
antiapoptotic
BCL-2
proteins,
due
challenges
in
elucidating
mechanism
activation
and
identifying
druggable
surfaces
BAX.
Here,
we
discuss
recent
studies
that
have
provided
structure-function
insights
identified
regulatory
control
activation.
Moreover,
emphasize
small
molecule
orthosteric,
allosteric,
oligomerization
modulators
provide
novel
opportunities
biological
investigation
progress
towards
drugging
Circulation,
Год журнала:
2023,
Номер
147(19), С. 1444 - 1460
Опубликована: Март 29, 2023
Myocardial
ischemia-reperfusion
(I/R)
injury
causes
cardiac
dysfunction
to
myocardial
cell
loss
and
fibrosis.
Prevention
of
death
is
important
protect
function
after
I/R
injury.
The
process
reperfusion
can
lead
multiple
types
cardiomyocyte
death,
including
necrosis,
apoptosis,
autophagy,
ferroptosis.
However,
the
time
point
at
which
various
modes
occur
mechanisms
underlying
ferroptosis
regulation
in
cardiomyocytes
are
still
unclear.Using
a
left
anterior
descending
coronary
artery
ligation
mouse
model,
we
sought
investigate
To
discover
key
molecules
involved
ferroptosis,
performed
metabolomics
study.
Loss/gain-of-function
approaches
were
used
understand
role
15-lipoxygenase
(Alox15)
peroxisome
proliferator-activated
receptor
gamma
coactivator
1-alpha
(Pgc1α)
injury.We
found
that
apoptosis
necrosis
occurred
early
phase
injury,
was
predominant
form
during
prolonged
reperfusion.
Metabolomic
profiling
eicosanoids
revealed
Alox15
metabolites
accumulated
ferroptotic
cardiomyocytes.
We
demonstrated
expression
specifically
increased
injured
area
ventricle
below
suture
colocalized
with
Furthermore,
myocardial-specific
knockout
mice
alleviated
restored
function.
15-Hydroperoxyeicosatetraenoic
acid
(15-HpETE),
an
intermediate
metabolite
derived
from
arachidonic
by
Alox15,
identified
as
trigger
for
explored
mechanism
its
effects
15-HpETE
promoted
binding
Pgc1α
ubiquitin
ligase
ring
finger
protein
34,
leading
ubiquitin-dependent
degradation.
Consequently,
attenuated
mitochondrial
biogenesis
abnormal
morphology
observed.
ML351,
specific
inhibitor
level
Pgc1α,
inhibited
protected
myocardium,
caused
recovery.Together,
our
results
established
Alox15/15-HpETE-mediated
plays
Cell Death and Disease,
Год журнала:
2021,
Номер
12(4)
Опубликована: Март 17, 2021
Ferroptosis
is
a
newly
recognised
type
of
regulated
cell
death
(RCD)
characterised
by
iron-dependent
accumulation
lipid
peroxidation.
It
significantly
distinct
from
other
RCDs
at
the
morphological,
biochemical,
and
genetic
levels.
Recent
reports
have
implicated
ferroptosis
in
multiple
diseases,
including
neurological
disorders,
kidney
injury,
liver
cancer.
Ferroptotic
has
also
been
associated
with
dysfunction
intestinal
epithelium,
which
contributes
to
several
diseases.
Research
on
may
provide
new
understanding
disease
pathogenesis
that
benefits
clinical
treatment.
In
this
review,
we
an
overview
its
underlying
mechanisms,
then
describe
emerging
role
ischaemia/reperfusion
(I/R)
inflammatory
bowel
(IBD),
colorectal
cancer
(CRC).
Redox Biology,
Год журнала:
2021,
Номер
45, С. 102021 - 102021
Опубликована: Июнь 1, 2021
Ferroptosis
is
a
programmed
iron-dependent
cell
death
associated
with
peroxidation
of
lipids
particularly,
phospholipids.
Several
studies
suggested
possible
contribution
mitochondria
to
ferroptosis
although
the
mechanisms
underlying
mitochondria-mediated
ferroptotic
pathways
remain
elusive.
Reduced
glutathione
(GSH)
central
player
in
that
required
for
peroxidase
4
eliminate
oxidized
Mitochondria
do
not
produce
GSH,
and
transport
GSH
fully
understood,
two
carrier
proteins,
dicarboxylate
(DIC,
SLC25A10)
oxoglutarate
(OGC,
SLC25A11)
have
been
participate
transport.
Here,
we
elucidated
role
DIC
OGC
as
well
mitochondrial
bioenergetics
H9c2
cardioblasts.
Results
showed
are
highly
sensitive
stimuli
displaying
fragmentation,
lipid
shortly
after
onset
stimulus.
Inhibition
electron
chain
complexes
oxidative
phosphorylation
worsened
RSL3-induced
ferroptosis.
LC-MS/MS
analysis
revealed
dramatic
increase
levels
pro-ferroptotic
oxygenated
phosphatidylethanolamine
species
response
RSL3
(ferroptosis
inducer)
cardiac
ischemia-reperfusion.
aggravated
increased
ROS,
membrane
depolarization,
depletion.
Dihydrolipoic
acid,
an
essential
cofactor
several
multienzyme
complexes,
attenuated
induced
direct
reduction
peroxidized
phospholipids
hydroxy-phospholipids
vitro.
In
conclusion,
suggest
diminishes
stimulates
depletion
inactivation
leading
Journal of Clinical Investigation,
Год журнала:
2021,
Номер
131(5)
Опубликована: Фев. 28, 2021
Immune
checkpoint
inhibitors
(ICIs)
have
transformed
the
treatment
of
various
cancers,
including
malignancies
once
considered
untreatable.
These
agents,
however,
are
associated
with
inflammation
and
tissue
damage
in
multiple
organs.
Myocarditis
has
emerged
as
a
serious
ICI-associated
toxicity,
because,
while
seemingly
infrequent,
it
is
often
fulminant
lethal.
The
underlying
basis
myocarditis
not
completely
understood.
While
importance
T
cells
clear,
inciting
antigens,
why
they
recognized,
mechanisms
leading
to
cardiac
cell
injury
remain
poorly
characterized.
issues
underscore
need
for
basic
clinical
studies
define
pathogenesis,
identify
predictive
biomarkers,
improve
diagnostic
strategies,
develop
effective
treatments.
An
improved
understanding
will
provide
insights
into
equilibrium
between
immune
cardiovascular
systems.
Experimental and Therapeutic Medicine,
Год журнала:
2022,
Номер
23(6)
Опубликована: Май 6, 2022
Myocardial
infarction
is
one
of
the
primary
causes
mortality
in
patients
with
coronary
heart
disease
worldwide.
Early
treatment
acute
myocardial
restores
blood
supply
ischemic
myocardium
and
decreases
risk.
However,
when
interrupted
recovered
within
a
certain
period
time,
it
more
serious
damage
to
original
myocardium;
this
known
as
ischemia/reperfusion
injury
(MIRI).
The
pathophysiological
mechanisms
leading
MIRI
are
associated
oxidative
stress,
intracellular
calcium
overload,
energy
metabolism
disorder,
apoptosis,
endoplasmic
reticulum
autophagy,
pyroptosis,
necroptosis
ferroptosis.
These
interplay
another
directly
or
indirectly
lead
aggravation
effect.
In
past,
apoptosis
autophagy
have
attracted
attention
but
ferroptosis
also
serve
key
roles.
mechanism
has
not
been
fully
elucidated.
present
study
reviews
underlying
MIRI.
Based
on
current
understanding
MIRI,
association
between
cell
death‑associated
signaling
pathways
were
elaborated,
providing
direction
for
investigation
novel
targets
clinical
treatment.
Signal Transduction and Targeted Therapy,
Год журнала:
2022,
Номер
7(1)
Опубликована: Авг. 15, 2022
Abstract
Myocardial
ischemia/reperfusion
(I/R)
injury
is
a
classic
type
of
cardiovascular
disease
characterized
by
to
cardiomyocytes
leading
various
forms
cell
death.
It
believed
that
irreversible
myocardial
damage
resulted
from
I/R
occurs
due
oxidative
stress
evoked
during
the
reperfusion
phase.
Here
we
demonstrate
ischemia
triggers
specific
redox
reaction
polyunsaturated
fatty
acids
(PUFA)-phospholipids
in
cells,
which
acts
as
priming
signaling
initiates
outbreak
robust
Using
animal
and
vitro
models,
crucial
lipid
species
were
identified
be
oxidized
PUFAs
enriched
phosphatidylethanolamines.
multi-omics,
arachidonic
acid
15-lipoxygenase-1
(ALOX15)
was
primary
mediator
ischemia-provoked
phospholipid
peroxidation,
further
confirmed
using
chemogenetic
approaches.
Collectively,
our
results
reveal
ALOX15
induction
phase
“burning
point”
ignite
oxidization
into
ferroptotic
signals.
This
finding
characterizes
novel
molecular
mechanism
for
offers
potential
therapeutic
target
early
intervention
injury.
Frontiers in Oncology,
Год журнала:
2020,
Номер
10
Опубликована: Сен. 25, 2020
Ferroptosis
is
a
newly
described
type
of
programmed
cell
death
and
intensively
related
to
both
maintaining
homeostasis
the
development
diseases,
especially
cancers.
Inducing
ferroptosis
leads
mitochondrial
dysfunction
toxic
lipid
peroxidation
in
cells,
which
plays
pivotal
role
suppressing
cancer
growth
progression.
Here,
we
reviewed
existing
studies
about
molecular
mechanisms
involved
different
antitumor
treatments,
such
as
chemotherapy,
targeted
therapy,
radiotherapy,
immunotherapy.
We
focused
particular
on
distinct
combinatorial
therapeutic
effects
synergistic
sensitization
effect
drug-resistance
reversal
achieved
when
using
inducers
with
conventional
therapy.
Finally,
discussed
challenges
opportunities
clinical
applications
ferroptosis.
The
application
nanotechnolgy
other
novel
technologies
may
provide
new
direction
ferroptosis-driven
therapies.