medRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Oct. 22, 2023
Abstract
Background
After
myocardial
infarction
(MI),
there
is
a
notable
disruption
in
cellular
calcium
ion
homeostasis
and
mitochondrial
function.
These
alterations
are
believed
to
be
linked
endoplasmic
reticulum
(ER)
stress,
though
the
specific
mechanisms
not
fully
understood.
This
research
endeavors
elucidate
involvement
of
glucose
regulated
protein
75
(GRP75)
post-MI
Results
Excessive
oxidative
stress
was
activated
humans’
post-myocardial
infarction,
with
most
differentially
expressed
genes
being
enriched
metabolic
pathways,
especially
signaling
pathway.
In
MI
rats,
symptoms
injury
were
accompanied
by
an
increase
activation
PERK,
ATF6,
IRE1,
as
well
elevated
Binding
immunoglobulin
(Bip)
expression.
Moreover,
oxygen-glucose
deprivation
(OGD)-induced
cardiomyocytes,
it
confirmed
that
inhibiting
PERK
exacerbated
intracellular
Ca
2+
cell
apoptosis.
More
importantly,
cardiomyocytes
undergoing
Tunicamycin-induced
ER
accumulated
both
mitochondria.
Concurrently,
co-localization
GRP75
IP3R
VDAC1
increased
under
cardiomyocytes.
OGD-induced
knockdown
only
reduced
levels
mitochondria
improved
ultrastructure
but
also
number
contact
points
between
mitochondria,
reducing
MAM
formation,
decreased
Significantly,
did
affect
expression
hypoxia-inducible
factor
1α
(HIF-1α).
Transcriptome
analysis
revealed
mainly
influenced
molecular
functions
sialyltransferase
IP3R,
biosynthesis
glycosphingolipids
lactate
metabolism.
lowered
transporter-1
(Glut1),
pyruvate
kinase
M2
(PKM2),
dehydrogenase
A
(LDHA),
products
glycolysis.
Conclusion
The
complex
interaction
driven
its
associated
IP3R1-GRP75-VDAC1
complex,
crucial
for
cardiomyocyte’s
adaptive
response
stress.
Modulating
could
offer
strategy
regulate
dynamics,
diminish
glycolysis,
thereby
mitigate
cardiomyocyte
Animals,
Journal Year:
2023,
Volume and Issue:
13(14), P. 2291 - 2291
Published: July 13, 2023
Widely
used
as
a
flame
retardant,
2,2'4,4'-tetrabromodiphenyl
ether
(BDE-47)
is
persistent
environmental
pollutant
with
toxicological
effects,
including
hepatotoxicity,
neurotoxicity,
reproductive
toxicity,
and
endocrine
disruption.
To
investigate
the
effects
of
BDE-47
on
early
porcine
embryogenesis
in
vitro,
cultured
embryos
were
exposed
to
during
development.
Exposure
100
μM
decreased
blastocyst
rate
mRNA
level
pluripotency
genes
but
increased
LC3
expression
autophagy-related
genes.
After
exposure,
embryos'
antioxidant
capability
decreased;
ROS
levels
increased,
while
glutathione
(GSH)
antioxidant-related
decreased.
In
addition,
exposure
reduced
mitochondrial
abundance
membrane
potential
levels,
downregulated
biogenesis-associated
genes,
endoplasmic
reticulum
(ER)
abundance,
GRP78,
marker
ER
stress
(ERS),
upregulated
ERS-related
However,
damage
low
embryo
quality
induced
by
reversed
ERS
inhibitor,
4-phenylbutyric
acid.
conclusion,
inhibits
development
vitro
inducing
dysfunction
ERS.
This
study
sheds
light
mechanisms
BDE-47-induced
embryonic
toxicity.
Chemistry,
Journal Year:
2024,
Volume and Issue:
6(3), P. 345 - 360
Published: April 25, 2024
The
conjugate
of
rhein
and
artesunate
have
shown
promising
effects
in
inducing
immunogenic
cell
death
(ICD)
inhibiting
tumor
growth.
Rhein,
a
natural
anthraquinone
derivative
found
various
medicinal
plants
such
as
Rheum
palmatum,
possesses
diverse
pharmacological
properties
including
anti-inflammatory
anticancer
activities.
Artesunate,
sesquiterpene
lactone
extracted
from
Artemisia
annua,
exhibits
potent
antimalarial
efficacy
has
garnered
attention
for
its
potential
properties.
Through
rational
drug
design,
the
conjugation
with
yielded
compounds
capable
selectively
targeting
mitochondria
cancer
cells,
oxidative
stress-mediated
ICD,
enhancing
immunogenicity
cells.
leverages
inherent
cytotoxicity
while
incorporating
capability
to
target
rhein,
thereby
fostering
special
approach
immunotherapy
cancer.
Upon
accumulation
mitochondria,
these
induce
generation
reactive
oxygen
species
(ROS),
leading
mitochondrial
membrane
(ΔΨm)
reduction
endoplasmic
reticulum
(ER)
stress.
Notably,
far
more
ICD-inducing
than
their
parent
compounds.
In
vivo
studies
demonstrated
that
vaccine,
when
treated
conjugate,
effectively
suppresses
medRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Oct. 22, 2023
Abstract
Background
After
myocardial
infarction
(MI),
there
is
a
notable
disruption
in
cellular
calcium
ion
homeostasis
and
mitochondrial
function.
These
alterations
are
believed
to
be
linked
endoplasmic
reticulum
(ER)
stress,
though
the
specific
mechanisms
not
fully
understood.
This
research
endeavors
elucidate
involvement
of
glucose
regulated
protein
75
(GRP75)
post-MI
Results
Excessive
oxidative
stress
was
activated
humans’
post-myocardial
infarction,
with
most
differentially
expressed
genes
being
enriched
metabolic
pathways,
especially
signaling
pathway.
In
MI
rats,
symptoms
injury
were
accompanied
by
an
increase
activation
PERK,
ATF6,
IRE1,
as
well
elevated
Binding
immunoglobulin
(Bip)
expression.
Moreover,
oxygen-glucose
deprivation
(OGD)-induced
cardiomyocytes,
it
confirmed
that
inhibiting
PERK
exacerbated
intracellular
Ca
2+
cell
apoptosis.
More
importantly,
cardiomyocytes
undergoing
Tunicamycin-induced
ER
accumulated
both
mitochondria.
Concurrently,
co-localization
GRP75
IP3R
VDAC1
increased
under
cardiomyocytes.
OGD-induced
knockdown
only
reduced
levels
mitochondria
improved
ultrastructure
but
also
number
contact
points
between
mitochondria,
reducing
MAM
formation,
decreased
Significantly,
did
affect
expression
hypoxia-inducible
factor
1α
(HIF-1α).
Transcriptome
analysis
revealed
mainly
influenced
molecular
functions
sialyltransferase
IP3R,
biosynthesis
glycosphingolipids
lactate
metabolism.
lowered
transporter-1
(Glut1),
pyruvate
kinase
M2
(PKM2),
dehydrogenase
A
(LDHA),
products
glycolysis.
Conclusion
The
complex
interaction
driven
its
associated
IP3R1-GRP75-VDAC1
complex,
crucial
for
cardiomyocyte’s
adaptive
response
stress.
Modulating
could
offer
strategy
regulate
dynamics,
diminish
glycolysis,
thereby
mitigate
cardiomyocyte
