ACOX1 activates autophagy via the ROS/mTOR pathway to suppress proliferation and migration of colorectal cancer
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Янв. 23, 2025
Acyl-CoA
oxidase
1
(ACOX1),
a
member
of
the
acyl-coenzyme
A
family,
is
considered
crucial
regulator
whose
dysregulation
implicated
in
occurrence
and
progression
various
cancers.
This
study
aims
to
elucidate
impact
ACOX1
CRC,
shedding
light
on
its
potential
as
therapeutic
target.
Through
analysis
GEO
dataset,
it
was
found
that
significantly
downregulated
colorectal
cancer
(CRC),
this
lower
expression
level
associated
with
worse
prognosis.
Additionally,
vitro
well
vivo,
overexpression
dramatically
reduced
proliferation
metastasis
CRC
cells.
Mass
spectrometry
revealed
role
fatty
acid
β-oxidation,
led
substantial
increase
reactive
oxygen
species
(ROS)
derived
from
β-oxidation.
Further
experiments
demonstrated
overexpression,
through
modulation
metabolism,
increased
ROS
levels,
phosphorylation
activation
key
autophagy
mTOR,
enhanced
autophagy,
ultimately
suppressed
growth
CRC.
In
conclusions,
decreased
may
regulate
by
reprogramming
lipid
metabolism
modulate
ROS/mTOR
signaling
pathway,
consequently
inhibiting
migration
Язык: Английский
Impaired peroxisomal beta-oxidation in microglia triggers oxidative stress and impacts neurons and oligodendrocytes
Ali Tawbeh,
Catherine Gondcaille,
Fatima-Ezzahra Saih
и другие.
Frontiers in Molecular Neuroscience,
Год журнала:
2025,
Номер
18
Опубликована: Янв. 30, 2025
Microglia,
the
immune
cells
of
central
nervous
system,
activate
neuroinflammatory
pathways
in
response
to
homeostatic
disturbances,
a
process
implicated
pathogenesis
various
neurodegenerative
diseases.
Emerging
evidence
identifies
abnormal
microglial
activation
as
causal
factor
at
onset
peroxisomal
leukodystrophies,
including
X-linked
adrenoleukodystrophy
(X-ALD).
This
study
investigates
how
primary
deficiencies
influence
oxidative
properties
microglia
and
examines
subsequent
impact
on
neurons
oligodendrocytes.
Using
BV-2
lacking
ABCD1,
ABCD2,
or
ACOX1,
proteins
that
play
key
roles
very-long-chain
fatty
acid
beta-oxidation,
we
analyzed
their
under
basal
condition
after
stimulation
by
lipopolysaccharide
(LPS).
Transcriptomic
analysis
mutant
revealed
numerous
differentially
expressed
genes,
particularly
redox-related
following
LPS
exposure.
These
changes
are
consistent
with
increased
production
reactive
oxygen
species
(ROS)
nitric
oxide
(NO).
Conditioned
media
(CM)
from
were
then
applied
cultures
neuron
oligodendrocyte
cell
lines.
Exposure
CM
LPS-stimulated
significantly
apoptosis
both
types.
Furthermore,
treated
exhibited
reduction
complexity
an
ability
secrete
neuropeptides.
findings
demonstrate
impairments
exacerbate
inflammatory
ROS/NO
production,
affecting
survival
oligodendrocytes,
well
neuronal
morphology
function.
dysfunction
might
contribute
early
events
X-ALD
triggering
sustaining
cascades.
Therapeutic
strategies
target
secretion
profiles
could
hold
promise
managing
disorders
such
X-ALD.
Язык: Английский
Analytical subcellular fractionation of microglial BV-2 cells with peroxisomal beta-oxidation defect
Histochemistry and Cell Biology,
Год журнала:
2025,
Номер
163(1)
Опубликована: Апрель 14, 2025
Язык: Английский
Interação dos receptores P2X7 e TRPV1 na ativação do inflamassoma NLRP3 e na liberação de vesículas extracelulares na linhagem murina de micróglia BV2
Опубликована: Май 13, 2024
Microglia
cells
are
the
resident
macrophages
of
central
nervous
system,
acting
as
primary
defense
line
and
highly
responsive
to
stress
stimuli.There
several
receptors
intracellular
pathways
involved
in
microglial
activation
process,
with
a
focus
on
P2X7
TRPV1
receptors,
two
sensors
activated
stressful
situations.P2X7
by
high
concentrations
ATP
LISTA
DE
ABREVIATURAS
2-AG2-araquidonoilglicerol
Язык: Английский
Anti-neuroinflammatory effects of conjugated linoleic acid isomers, c9,t11 and t10,c12, on activated BV-2 microglial cells
Frontiers in Cellular Neuroscience,
Год журнала:
2024,
Номер
18
Опубликована: Сен. 27, 2024
Conjugated
linoleic
acid
(CLA)
isomers
exhibit
anti-inflammatory
properties
within
the
central
nervous
system
(CNS).
This
study
investigated
effects
of
CLA
c9,t11
and
t10,c12
on
fatty
(FA)
N-
acylethanolamine
(NAE)
profiles
their
association
with
pro-inflammatory
molecule
expression
in
BV-2
microglia
cell
line,
CNS's
resident
immune
cells
responsible
for
maintaining
neuronal
activity
homeostasis.
were
treated
25
μM
c9,t11-CLA,
t10,c12-CLA,
or
oleic
(OA)
24
h,
followed
by
lipopolysaccharide
(LPS)
stimulation.
After
treatment,
cell's
FA
NAE
analyzed.
Our
results
demonstrated
that
mitigate
LPS-induced
morphological
changes
reduce
gene
protein
levels
inflammatory
markers.
effect
was
linked
to
an
upregulation
acyl-CoA
oxidase
1,
a
key
enzyme
peroxisomal
beta-oxidation
pathway
efficiently
metabolizes
isomers.
Notably,
t10,c12-CLA
significantly
suppressed
stearoyl-CoA
desaturase
impacting
monounsaturated
synthesis.
The
NAEs
profile
remarkably
altered
isomers,
significant
release
anti-neuroinflammatory
mediator
docosahexaenoic
(DHA)-derived
(DHAEA).
In
conclusion,
our
findings
suggest
are
due
unique
influences
metabolism
modulation
bioactive
FA-derived
NAEs,
highlighting
potential
strategy
nutritional
intervention
conditions
characterized
neuroinflammation.
Язык: Английский