DNA-Dependent Protein Kinase Catalytic Subunit Prevents Ferroptosis in Retinal Pigment Epithelial Cells
Investigative Ophthalmology & Visual Science,
Год журнала:
2025,
Номер
66(1), С. 50 - 50
Опубликована: Янв. 22, 2025
Purpose:
The
purpose
of
this
study
was
to
investigate
the
activated
core
kinases
involved
in
DNA
damage
responses
(DDR)
during
ferroptosis
retinal
pigment
epithelial
(RPE)
cells
vitro
and
their
regulatory
effects
on
ferroptosis.
Methods:
Ferroptosis
induced
by
erastin
RPE
(iRPE)
derived
from
human
umbilical
cord
mesenchymal
stem
(hUCMSCs),
hUCMSCs,
pluripotent
cell-derived
(iPSC-RPE)
cells.
CCK8
employed
measure
cell
viability.
Calcein/PI
staining
used
detect
ferroptotic
γ-H2AX,
8-oxoG,
phosphorylated
DNA-dependent
protein
kinase
catalytic
subunit
(DNA-PKcs)
were
determined
through
immunostaining.
phosphorylation
DNA-PKcs
ERK1/2
Western
blotting.
Lipid
peroxides
detected
BODIPY581/591-C11
staining.
Results:
iRPE
exhibited
a
stronger
ability
resist
compared
hUCMSCs.
cells,
rapidly
treatment
erastin.
In
addition,
inhibition
promoted
suggesting
that
prevents
Meanwhile,
inhibited
only
at
early
stage
induction,
whereas
played
protective
role
Furthermore,
inducing
its
promoting
also
verified
iPSC-RPE
Conclusions:
present
elucidates
key
DDR
is
plays
vitro,
which
will
provide
new
research
targets
strategies
for
inhibiting
Язык: Английский
Unveiling protective mechanisms of wild olive (acebuche) oil in retinal pigment epithelial cells with hypertensive phenotype
The Journal of Physiology,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 24, 2025
Abstract
Arterial
hypertension
leads
to
oxidative
and
inflammatory
imbalances,
triggering
hypertensive
organ
damage
through
several
pathways.
We
have
previously
described
the
antioxidant
anti‐inflammatory
properties
of
olive
oil
extracted
from
wild
tree
(
Olea
europaea
var.
sylvestris
,
acebuche,
ACE)
against
ocular
damage.
The
aim
this
study
was
clarify
molecular
mechanisms
involved
in
beneficial
effect
ACE
on
eyes,
focusing
nitric
oxide
(NO)/arginine
metabolism.
To
end,
we
used
retinal
pigment
epithelial
cells
(ARPE19)
treated
with
angiotensin
II
as
a
hypertensive‐like
model.
These
were
also
incubated
extracellular
vesicles
(EVs)
isolated
animals
fed
diets
enriched
either
or
extra
virgin
(EVOO),
latter
serving
reference
for
comparison.
Our
results
showed
that
circulating
oil‐
EVOO‐derived
EVs
can
modulate
production
reactive
oxygen
species
by
both
NADPH
oxidase
mitochondria,
activity
expression
l
‐arginine
transporter
CAT‐1,
AT1
AT2
receptors,
arginases,
well
levels
NO
asymmetric
dimethylarginine.
findings
demonstrate
that:
(1)
changes
metabolism
are
protective
effects
hypertension‐related
stress,
(2)
these
modifications
appear
be
mediated
EVs.
image
Key
points
‐Arginine
transport
contributes
eyes
mice.
Extravesicular
(ACE‐EVs)
prevent
(metabolism
cells.
Reactive
produced
mitochondria
mitigated
ACE‐EV
treatment.
Язык: Английский