Journal of Diabetes Research,
Год журнала:
2021,
Номер
2021, С. 1 - 10
Опубликована: Июнь 28, 2021
Ferroptosis
is
a
novel
form
of
nonapoptotic
regulated
cell
death
(RCD).
It
features
iron-dependent
lipid
peroxide
accumulation
accompanied
by
inadequate
redox
enzymes,
especially
glutathione
peroxidase
4
(GPX4).
RAS-selective
lethal
3
(RSL3),
erastin,
and
ferroptosis
inducing
56
(FIN56)
induce
via
different
manners
targeting
GPX4
function.
Acyl-CoA
synthetase
long-chain
family
(ACSL4),
lysophosphatidylcholine
acyltransferase
(LPCAT3),
lipoxygenases
(LOXs)
participate
in
the
production
peroxides.
Heat
shock
protein
B
member
1
(HSPB1)
nuclear
receptor
coactivator
(NCOA4)
regulate
iron
homeostasis
preventing
caused
high
concentration
intracellular
iron.
ubiquitous
our
body
as
it
exists
both
physiologic
pathogenic
processes.
involved
glucose-stimulated
insulin
secretion
(GSIS)
impairment
arsenic-induced
pancreatic
damage
pathogenesis
diabetes.
Moreover,
iron-sulfur
(Fe-S)
cluster
influence
each
other,
causing
mitochondrial
accumulation,
more
reactive
oxygen
species
(ROS)
production,
endoplasmic
reticulum
(ER)
stress,
failure
biosynthesis
insulin,
β-cells.
In
addition,
also
engages
diabetic
complications
such
myocardial
ischemia
cardiomyopathy
(DCM).
this
review,
we
summarize
mechanism
its
association
with
type
2
diabetes
mellitus
(T2DM).
Redox Biology,
Год журнала:
2018,
Номер
15, С. 490 - 503
Опубликована: Фев. 3, 2018
The
human
brain
consumes
20%
of
the
total
basal
oxygen
(O2)
budget
to
support
ATP
intensive
neuronal
activity.
Without
sufficient
O2
demands,
activity
fails,
such
that,
even
transient
ischemia
is
neurodegenerative.
While
essentiality
function
clear,
how
oxidative
stress
causes
neurodegeneration
ambiguous.
Ambiguity
exists
because
many
reasons
why
susceptible
remain
obscure.
Many
are
erroneously
understood
as
deleterious
result
adventitious
derived
free
radical
and
non-radical
species
generation.
To
understand
underpin
stress,
one
must
first
re-cast
in
a
positive
light
their
deliberate
generation
enables
achieve
critical
functions
(e.g.
synaptic
plasticity)
through
redox
signalling
(i.e.
functionality).
Using
radicals
derivatives
signal
sensitises
when
goes
awry
negative
advance
mechanistic
understanding,
we
rationalise
13
stress.
Key
include
inter
alia
unsaturated
lipid
enrichment,
mitochondria,
calcium,
glutamate,
modest
antioxidant
defence,
active
transition
metals
neurotransmitter
auto-oxidation.
We
review
RNA
oxidation
an
underappreciated
cause
complex
interplay
between
each
reason
dictates
susceptibility
dynamic
context
neural
identity
dependent
manner.
Our
discourse
sets
stage
for
investigators
interrogate
biochemical
basis
health
disease.
ACS Central Science,
Год журнала:
2019,
Номер
6(1), С. 41 - 53
Опубликована: Дек. 27, 2019
Ferroptosis
is
an
iron-dependent
form
of
regulated
cell
death
linking
iron,
lipid,
and
glutathione
levels
to
degenerative
processes
tumor
suppression.
By
performing
a
genome-wide
activation
screen,
we
identified
cohort
genes
antagonizing
ferroptotic
death,
including
GTP
cyclohydrolase-1
(GCH1)
its
metabolic
derivatives
tetrahydrobiopterin/dihydrobiopterin
(BH4/BH2).
Synthesis
BH4/BH2
by
GCH1-expressing
cells
caused
lipid
remodeling,
suppressing
ferroptosis
selectively
preventing
depletion
phospholipids
with
two
polyunsaturated
fatty
acyl
tails.
GCH1
expression
level
in
cancer
lines
stratified
susceptibility
ferroptosis,
accordance
human
samples.
The
GCH1-BH4-phospholipid
axis
acts
as
master
regulator
resistance,
controlling
endogenous
production
the
antioxidant
BH4,
abundance
CoQ10,
peroxidation
unusual
This
demonstrates
unique
mechanism
protection
that
independent
GPX4/glutathione
system.
Abstract
Ferroptosis
is
an
intracellular
iron-dependent
form
of
cell
death
that
distinct
from
apoptosis,
necrosis,
and
autophagy.
Extensive
studies
suggest
ferroptosis
plays
a
pivotal
role
in
tumor
suppression,
thus
providing
new
opportunities
for
cancer
therapy.
The
development
resistance
to
therapy
remains
major
challenge.
A
number
preclinical
clinical
have
focused
on
overcoming
drug
resistance.
Intriguingly,
has
been
correlated
with
resistance,
inducing
demonstrated
reverse
Herein,
we
provide
detailed
description
the
mechanisms
therapeutic
regulating
reversing
common
therapies,
such
as
chemotherapy,
targeted
immunotherapy.
We
discuss
prospect
challenge
strategy
expect
our
review
could
some
references
further
studies.
Cell Death and Differentiation,
Год журнала:
2019,
Номер
26(11), С. 2284 - 2299
Опубликована: Фев. 8, 2019
Ferroptosis
is
a
recently
identified
form
of
regulated
cell
death
defined
by
the
iron-dependent
accumulation
lipid
reactive
oxygen
species.
has
been
studied
in
various
diseases
such
as
cancer,
Parkinson's
disease,
and
stroke.
However,
exact
function
mechanism
ferroptosis
ischemia/reperfusion
(I/R)
injury,
especially
intestine,
remains
unknown.
Considering
unique
conditions
required
for
ferroptosis,
we
hypothesize
that
ischemia
promotes
immediately
after
intestinal
reperfusion.
In
contrast
to
conventional
strategies
employed
I/R
studies,
focused
on
ischemic
phase.
Here
verified
assessing
proferroptotic
changes
along
with
protein
peroxidation
levels
during
The
inhibition
liproxstatin-1
ameliorated
I/R-induced
injury.
Acyl-CoA
synthetase
long-chain
family
member
4
(ACSL4),
which
key
enzyme
regulates
composition,
shown
contribute
execution
but
its
role
needs
clarification.
present
study,
used
rosiglitazone
(ROSI)
siRNA
inhibit
ischemia/hypoxia-induced
ACSL4
vivo
vitro.
results
demonstrated
before
reperfusion
protected
against
death.
Further
investigation
revealed
special
1
(Sp1)
was
crucial
transcription
factor
increased
binding
promoter
region.
Collectively,
this
study
demonstrates
closely
associated
critical
lethal
process.
Sp1
an
important
promoting
expression.
These
suggest
effective
mechanistic
approach
injury
prevention
treatment.
Redox Biology,
Год журнала:
2019,
Номер
28, С. 101328 - 101328
Опубликована: Сен. 20, 2019
Ferroptosis
is
a
form
of
cell
death
primed
by
iron
and
lipid
hydroperoxides
prevented
GPx4.
Ferrostatin-1
(fer-1)
inhibits
ferroptosis
much
more
efficiently
than
phenolic
antioxidants.
Previous
studies
on
the
antioxidant
efficiency
fer-1
adopted
kinetic
tests
where
diazo
compound
generates
hydroperoxyl
radical
scavenged
antioxidant.
However,
this
reaction,
accounting
for
chain
breaking
effect,
only
minimally
useful
description
inhibition
ferrous
hydroperoxide
dependent
peroxidation.
Scavenging
radicals,
indeed,
from
which
initiates
new
peroxidative
reaction.
We
show
that
when
peroxidation,
initiated
traces
in
liposomes,
pattern
oxidized
species
produced
pre-existing
practically
identical
to
observed
following
exhaustive
peroxidation
absence
This
supported
notion
anti-ferroptotic
activity
actually
due
scavenging
initiating
alkoxyl
radicals
produced,
together
with
other
rearrangement
products,
hydroperoxides.
Notably,
not
consumed
while
inhibiting
The
emerging
concept
it
itself
reduces
radical.
was
electroanalytical
evidence
forms
complex
further
confirmed
cells
fluorescence
calcein,
indicating
decrease
labile
presence
fer-1.
such
as
pseudo-catalytic
cycle
ferrostatin-iron
also
investigated
means
quantum
mechanics
calculations,
reduction
an
model
iron.
In
summary,
GPx4
iron,
produces,
distinct
mechanism,
most
relevant
i.e
disappearance
Journal of Cellular and Molecular Medicine,
Год журнала:
2019,
Номер
23(8), С. 4900 - 4912
Опубликована: Июнь 24, 2019
Abstract
Ferroptosis
is
a
newly
defined
programmed
cell
death
process
with
the
hallmark
of
accumulation
iron‐dependent
lipid
peroxides.
The
term
was
first
coined
in
2012
by
Stockwell
Lab,
who
described
unique
type
induced
small
molecules
erastin
or
RSL3.
distinct
from
other
already
established
and
has
morphological
bioenergetic
features.
physiological
role
ferroptosis
during
development
not
been
well
characterized.
However,
shows
great
potentials
cancer
therapy.
Great
progress
made
exploring
mechanisms
ferroptosis.
In
this
review,
we
focus
on
molecular
ferroptosis,
functioning
initiation
sensitivity
different
cancers.
We
are
also
concerned
new
arising
questions
particular
research
area
that
remains
unanswered.
