AdipoRon ameliorates chronic ethanol induced cardiac necroptosis by reducing ceramide mediated mtROS
Free Radical Biology and Medicine,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 1, 2025
Язык: Английский
Phosphoglycerate mutase 5 exacerbates alcoholic cardiomyopathy in male mice by inducing prohibitin‐2 dephosphorylation and impairing mitochondrial quality control
Clinical and Translational Medicine,
Год журнала:
2024,
Номер
14(8)
Опубликована: Авг. 1, 2024
The
induction
of
mitochondrial
quality
control
(MQC)
mechanisms
is
essential
for
the
re-establishment
homeostasis
and
cellular
bioenergetics
during
periods
stress.
Although
MQC
activation
has
cardioprotective
effects
in
various
cardiovascular
diseases,
its
precise
role
regulatory
alcoholic
cardiomyopathy
(ACM)
remain
incompletely
understood.
Язык: Английский
Astragaloside IV alleviates septic myocardial injury through DUSP1-Prohibitin 2 mediated mitochondrial quality control and ER-autophagy
Journal of Advanced Research,
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 1, 2024
Septic
cardiomyopathy
(SCM)
is
a
complication
of
myocardial
injury
in
patients
with
severe
sepsis.
This
study
highlights
the
potential
Astragaloside
IV(AS)
treatment
septic
and
provides
reference
for
developing
cardioprotective
drugs
targeting
DUSP1-PHB2-related
mitochondria-ER
interaction.
Dual
specificity
phosphatase-1
(DUSP1)/Prohibitin
2
cardiomyocyte-specific
knockout
mice
(DUSP1/PHB2CKO)
/DUSP1
transgenic
(DUSP1/PHB2TG)
were
used
to
generate
LPS-induced
sepsis
models.
The
pathological
mechanism
by
which
AS-IV
improves
heart
was
detected
using
cardiac
ultrasound,
fluorescence
staining,
transmission
electron
microscopy,
western
blotting.
After
siRNA
cardiomyocytes
DUSP-1/PHB2,
changes
mitochondrial
function
morphology
determined
qPCR,
blotting,
ELISA,
laser
confocal
targeted
therapeutic
effects
further
examined.
SCM
leads
dysfunction.
However,
IV
(AS)
normalizes
homeostasis
ER
function.
Notably,
protective
effect
blocked
DUSP1/Prohibitin
but
remained
unaffected
DUSP1
(DUSP1/PHB2TG).
AS
DUSP1-PHB2
related
Язык: Английский
The UCP2/PINK1/LC3B-mediated Mitophagy is involved in the Protection of NRG1 against Myocardial Ischemia/Reperfusion Injury
Redox Biology,
Год журнала:
2025,
Номер
unknown, С. 103511 - 103511
Опубликована: Янв. 1, 2025
Язык: Английский
Targeting mitochondria by lipid-selenium conjugate drug results in malate/fumarate exhaustion and induces mitophagy-mediated necroptosis suppression
International Journal of Biological Sciences,
Год журнала:
2024,
Номер
20(14), С. 5793 - 5811
Опубликована: Окт. 28, 2024
Atherosclerosis
(AS)
is
a
chronic
vascular
disease
primarily
affecting
large
and
medium-sized
arteries
involves
various
complex
pathological
mechanisms
factors.
Previous
studies
have
demonstrated
close
association
between
atherosclerosis
inflammatory
damage,
metabolic
disorders,
gut
microbiota.
It
also
closely
linked
to
several
cellular
processes,
such
as
endothelial
cell
pyroptosis,
ferroptosis,
mitophagy,
mitochondrial
dynamics,
biogenesis.
Mitophagy
has
been
recognized
previously
unexplored
mechanism
contributing
injury
in
atherosclerosis.
Our
study
aims
further
elucidate
the
potential
relationship
AS-induced
mitophagy
dysfunction
interaction
of
TMBIM6
NDUFS4.
Data
from
that
AS
mice
was
associated
with
substantial
activation
oxidative
stress
along
marked
reduction
expression
increased
fission,
leading
homeostasis
disruption.
However,
under
pharmacological
intervention,
levels
significantly
increased,
fission
notably
reduced,
damage
were
suppressed,
while
necroptotic
pathways
cells
blocked.
Interestingly,
deletion
or
NDUFS4
animal
models
lines
markedly
impaired
therapeutic
effects
drug,
disrupting
its
regulation
re-emergence
responses
damage.
Metabolomics
analysis
revealed
autophagy
plays
pivotal
regulatory
role
during
drug
intervention
after
genetic
modification
The
(macroautophagy/mitophagy)
alleviated
negative
induced
by
lipid
cells,
likely
TMBIM6-NDUFS4
axis.
Subsequent
gene
experiments
knocking
out
negates
on
lipid-induced
function.
In
summary,
our
research
reveals
phenotypic
through
influenced
Pharmacological
can
restore
regulating
via
pathway.
This
novel
insight
suggests
may
serve
key
target
for
Язык: Английский
High-Throughput Screening of an FDA-Approved Compound Library Reveals a Novel GAS6 Receptor Agonist for Therapeutic Intervention in Septic Myocardial and microvascular Injury via Modulation of Danger-Associated Molecular Patterns
International Journal of Biological Sciences,
Год журнала:
2024,
Номер
20(15), С. 6222 - 6240
Опубликована: Ноя. 11, 2024
PGAM5
and
VDAC1
have
both
been
reported
to
regulate
mitophagy.
However,
the
mechanisms
by
which
they
sepsis-induced
inflammatory
microvascular
injury
remain
unverified.
In
previous
studies,
we
established
role
of
this
regulatory
axis
in
various
phenotypic
processes,
including
mitophagy,
mitochondrial
biogenesis,
unfolded
protein
response,
dynamics,
while
further
confirming
interactive
proteins
within
axis.
validation
elucidation
these
phenotypes
primarily
focused
on
ischemic
heart
diseases
such
as
myocardial
failure.
Sepsis-related
is
currently
recognized
a
significant
cardiac
impairment,
although
there
are
cardioprotective
nutritional
agents
available
for
supportive
therapy,
fundamental
research
validating
upstream
targets
still
lacking.
Based
our
research,
explored
mitophagy
dysfunction
mediated
its
coronary
injury.
We
also
confirmed
material
basis
metabolic
pathway
regulation
targeting
PGAM5-
mechanism
with
relevant
drugs.
Our
findings
suggest
that
PGAM5-mediated
may
be
crucial
factor
leading
injury,
interacting
VDAC1-mediated
membrane
dysfunction.
Animal
experiments
revealed
cardiac-specific
knockout
could
reverse
LPS-induced
damage,
restoring
ejection
function
functionality.
vitro
studies
PGAM5-VDAC1
interaction
can
normalize
normal
morphology
structure
mitochondria
maintaining
energy
metabolism
levels
respiratory
chain
function.
Further
pharmacological
indicated
active
ingredients
traditional
Chinese
medicine-Puerarin
(TCM,
GAS6
Receptor
Agonist)
target
inhibit
necrotic
apoptosis
cardiomyocytes,
potentially
reversing
pathway-related
TCM
emerge
prospective
therapeutic
agent
Язык: Английский
Neuregulin-1 Attenuates Myocardial Ischemia/Reperfusion Injury by Activating the UCP2/PINK1/LC3B-mediated Mitophagy
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 9, 2024
Abstract
BACKGROUND
Ischemia/reperfusion
(I/R)
injury
may
significantly
affect
the
treatment
outcomes
and
prognosis
of
patients
with
acute
myocardial
infarction
following
coronary
artery
recanalization.
Available
evidence
suggests
that
neuregulin-1
(NRG-1)
can
provide
a
protection
against
I/R
is
involved
in
various
cardioprotective
interventions
by
potential
regulation
mitophagy.
However,
molecular
mechanisms
linking
NRG-1
mitophagy
remain
to
be
clarified.
This
experiment
aimed
determine
whether
postconditioning
attenuated
through
explore
underlying
mechanisms.
METHOD
Both
an
vivo
model
rats
vitro
hypoxia/reoxygenation
(H/R)
H9C2
cardiomyocytes
were
applied.
was
conducted
immediately
after
or
H/R
intervention.
In
experiment,
effects
determined
infarct
size,
cardiac
enzyme
histopathologic
examinations.
The
downstream
pathways
targets
screened
RNA
sequencing
Protein-Protein
Interaction
Networks
(PPI).
expression
levels
mitochondrial
uncoupling
protein
2
(UCP2)
mitophagy-related
both
myocardium
measured
immunofluorescence
staining
Western
blots.
activation
observed
transmission
electron
microscopy
(TEM)
JC-1
staining.
RESULTS
KEGG
GSEA
analyses
showed
enriched
treated
NRG-1,
UCP2
exhibited
significant
correlation
between
interaction
PINK1.
Meanwhile,
inhibitor
Mdivi-1
eliminated
,
challenge
genipin
could
also
attenuate
activating
effect
on
Consistently,
using
showd
up-regulated
proteins,
activated
mitophagy,
whereas
small
interfering
(siRNA)-mediated
knockdown
abolished
NRG-1.
CONCLUSIONS
produce
UCP2/PINK1/LC3B
signaling
pathway.
Язык: Английский