Nicotinamide mononucleotide combined with PJ-34 protects microglial cells from lipopolysaccharide-induced mitochondrial impairment through NMNAT3-PARP1 axis
Journal of Translational Medicine,
Год журнала:
2025,
Номер
23(1)
Опубликована: Март 6, 2025
Lipopolysaccharide
(LPS)
is
known
to
induce
cell
injury
and
mitochondrial
dysfunction,
which
are
pivotal
in
neuroinflammation
related
disorders.
Recent
studies
have
demonstrated
the
potential
of
nicotinamide
mononucleotide
(NMN)
poly(ADP-ribose)
polymerase-1
(PARP1)
inhibitors
enhance
function.
However,
underlying
mechanisms
not
been
fully
elucidated.
This
study
investigates
impact
NMN
conjunction
with
PJ-34,
a
PARP1
inhibitor,
on
LPS-induced
damage,
focusing
adenylyl
transferase
3
(NMNAT3)
-PARP1
axis.
The
results
showed
that
LPS
treatment
led
down-regulation
NMNAT3
(decreased
58.72%
at
1
µM),
up-regulation
(enhanced
22.78%
thereby
impairing
mitophagy
negative
effects
can
be
mitigated
through
supplementation
PJ-34.
Specifically,
compared
group,
expression
increased
by
63.29%
decreased
27.94%
concentration
400
µM
NMN.
Additionally,
when
was
combined
5
21.99%.
Mechanistic
reveal
PJ-34
counteracted
detrimental
promoting
binding
FoxO1
PINK1
promoter
activate
PINK1/Parkin
mediated
pathway.
Further
experimental
demonstrate
inhibit
initiation
autophagic
processes.
Consequently,
targeting
NMNAT3-PARP1
signaling
pathway
holds
promise
for
development
novel
therapeutic
strategies
alleviate
damage-related
Язык: Английский
Trends in intestinal aging: From underlying mechanisms to therapeutic strategies
Acta Pharmaceutica Sinica B,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 1, 2025
Язык: Английский
β-Nicotinamide Mononucleotide Reduces Oxidative Stress and Improves Steroidogenesis in Granulosa Cells Associated with Sheep Prolificacy via Activating AMPK Pathway
Antioxidants,
Год журнала:
2024,
Номер
14(1), С. 34 - 34
Опубликована: Дек. 30, 2024
Oxidative
stress
is
a
significant
factor
in
the
death
of
granulosa
cells
(GCs),
leading
to
follicular
atresia
and
consequently
limiting
number
dominant
follicles
that
can
mature
ovulate
within
each
wave.
Follicular
fluid
contains
diverse
array
metabolites
play
crucial
roles
regulating
GCs’
proliferation
oocyte
maturation,
which
are
essential
for
follicle
development
female
fertility.
However,
mechanisms
behind
metabolite
heterogeneity
its
effects
on
function
remain
poorly
understood.
Here,
we
identified
elevated
nicotinamide
levels
high-prolificacy
sheep,
correlated
with
oxidative
GCs,
by
an
integrated
analysis.
In
vitro
experiments
demonstrated
supplementation
β-nicotinamide
mononucleotide
(NMN)
significantly
increased
adenine
dinucleotide
(NAD+)
adenosine
triphosphate
(ATP)
GCs.
NMN
treatment
effectively
reduced
Lipopolysaccharide
(LPS)-induced
apoptosis
mitigated
mitochondrial
dysfunction,
while
also
decreasing
production
reactive
oxygen
species
(ROS),
thereby
enhancing
activity
antioxidant
defense
system.
Importantly,
improved
impairments
steroid
hormone
induced
LPS.
Mechanistically,
protective
against
GCs
were
mediated
via
AMPK/mTOR
pathway.
Collectively,
our
findings
elucidate
metabolic
characteristics
associated
sheep
prolificacy
demonstrate
protects
from
LPS-induced
dysfunction
enhances
ovarian
responsiveness
These
position
as
potential
novel
biomarker
function.
Язык: Английский