BBA Advances,
Год журнала:
2023,
Номер
4, С. 100105 - 100105
Опубликована: Янв. 1, 2023
INPP5K
(inositol
polyphosphate
5-phosphatase
K)
is
an
endoplasmic
reticulum
(ER)-resident
enzyme
that
acts
as
a
phosphoinositide
(PI)
5-phosphatase,
capable
of
dephosphorylating
various
PIs
including
PI
4,5-bisphosphate
(PI(4,5)P2),
key
found
in
the
plasma
membrane.
Given
its
ER
localization
and
substrate
specificity,
may
play
role
ER-plasma
membrane
contact
sites.
Furthermore,
PI(4,5)P2
serves
for
phospholipase
C,
activated
downstream
extracellular
agonists
acting
on
Gq-coupled
receptors
or
tyrosine-kinase
receptors,
leading
to
IP3
production
subsequent
release
Ca2+
from
ER,
primary
intracellular
storage
organelle.
In
this
study,
we
investigated
impact
dynamics
using
previously
established
INPP5K-knockdown
U-251
MG
glioblastoma
cell
model.
We
here
describe
loss
impairs
agonist-induced,
receptor
(IP3R)-mediated
mobilization
intact
cells,
while
content
store-operated
influx
remain
unaffected.
To
further
elucidate
underlying
mechanisms,
examined
permeabilized
cells
stimulated
with
exogenous
IP3.
Interestingly,
absence
also
disrupted
IP3-induced
events.
These
results
suggest
directly
influence
IP3R
activity
through
mechanisms
yet
be
resolved.
The
findings
study
point
towards
modulating
calcium
dynamics,
particularly
relation
IP3-mediated
signaling
pathways.
However,
work
needed
establish
general
nature
our
unravel
exact
molecular
interplay
between
INNP5K
function
signaling.
ACS Nano,
Год журнала:
2024,
Номер
18(18), С. 11778 - 11803
Опубликована: Апрель 23, 2024
Severe
acute
pancreatitis
(AP)
is
a
life-threatening
pancreatic
inflammatory
disease
with
high
mortality
rate
(∼40%).
Existing
pharmaceutical
therapies
in
development
or
clinical
trials
showed
insufficient
treatment
efficacy
due
to
their
single
molecular
therapeutic
target,
poor
water
solubility,
short
half-life,
limited
pancreas-targeting
specificity,
etc.
Herein,
acid-responsive
hollow
mesoporous
Prussian
blue
nanoparticles
wrapped
neutrophil
membranes
and
surface
modified
the
N,N-dimethyl-1,3-propanediamine
moiety
were
developed
for
codelivering
membrane-permeable
calcium
chelator
BAPTA-AM
(BA)
trypsin
activity
inhibitor
gabexate
mesylate
(Ga).
In
AP
mouse
model,
formulation
exhibited
efficient
recruitment
at
endothelium,
trans-endothelial
migration,
precise
acinar
cell
targeting,
resulting
rapid
localization
higher
accumulation.
A
low
dose
of
(BA:
200
μg
kg–1,
Ga:
0.75
mg
kg–1)
significantly
reduced
pancreas
function
indicators
close
normal
levels
24
h,
effectively
restored
redox
status,
apoptotic
proportion,
blocked
systemic
amplified
cascade,
dramatic
increase
survival
from
58.3
even
100%.
Mechanistically,
inhibited
endoplasmic
reticulum
stress
(IRE1/XBP1
ATF4/CHOP
axis)
impaired
autophagy
(Beclin-1/p62/LC3
axis),
thereby
preserving
dying
cells
restoring
cellular
"health
status".
This
provides
an
upstream
strategy
translation
prospects
management
through
synergistic
ion
homeostasis
regulation
autodigestion
inhibition.
Biomedicine & Pharmacotherapy,
Год журнала:
2024,
Номер
174, С. 116574 - 116574
Опубликована: Апрель 8, 2024
Gastrointestinal
(GI)
cancer
is
one
of
the
most
severe
types
cancer,
with
a
significant
impact
on
human
health
worldwide.
Due
to
urgent
demand
for
more
effective
therapeutic
strategies
against
GI
cancers,
novel
research
metal
ions
treating
cancers
has
attracted
increasing
attention.
Currently,
accumulating
relationship
between
and
therapy,
several
have
been
discovered
induce
cell
death.
In
particular,
three
modes
death,
including
ferroptosis,
cuproptosis,
calcicoptosis,
become
focal
points
in
field
cancer.
Meanwhile,
other
also
found
trigger
death
through
various
mechanisms.
Accordingly,
this
review
focuses
mechanisms
ion-induced
hoping
provide
theoretical
support
further
therapies.
Pharmacology & Therapeutics,
Год журнала:
2024,
Номер
254, С. 108594 - 108594
Опубликована: Янв. 28, 2024
Cerebral
dopamine
neurotrophic
factor
(CDNF)
is
an
endogenous
protein
in
humans
and
other
vertebrates,
it
has
been
shown
to
have
protective
restorative
effects
on
cells
various
disease
models.
Although
named
as
a
factor,
its
actions
are
drastically
different
from
classical
factors
such
neurotrophins
or
the
glial
cell
line-derived
family
of
proteins.
Like
all
secreted
proteins,
CDNF
signal
sequence
at
N-terminus,
but
unlike
common
growth
KDEL-receptor
retrieval
C-terminus.
Thus,
mainly
located
ER.
In
response
adverse
effects,
ER
stress,
expression
upregulated
can
alleviate
stress.
Also
factors,
reduces
aggregation
inflammation
luminal
protein,
surprisingly
directly
interact
with
alpha-synuclein,
involved
pathogenesis
synucleinopathies
e.g.,
Parkinson's
disease.
Pleiotropic
therapeutic
potential
tested
recombinant
human
gene
therapy.
The
neuroprotective
neurorestorative
described
number
preclinical
studies
disease,
stroke
amyotrophic
lateral
sclerosis.
Currently,
was
successfully
evaluated
for
safety
phase
1/2
clinical
trial
Collectively,
based
recent
findings
mode
action
CDNF,
use
drug
could
be
expanded
stress-related
diseases.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Март 9, 2024
Abstract
Endoplasmic/sarcoplasmic
reticulum
(ER/SR)
sits
at
the
heart
of
calcium
(Ca
2+
)
signaling
machinery,
yet
current
genetically
encoded
Ca
indicators
(GECIs)
lack
ability
to
detect
elementary
release
events
from
ER/SR,
particularly
in
muscle
cells.
Here
we
report
a
set
organellar
GECIs,
termed
NEMOer,
efficiently
capture
ER
dynamics
with
increased
sensitivity
and
responsiveness.
Compared
G-CEPIA1er,
NEMOer
exhibit
dynamic
ranges
that
are
an
order
magnitude
larger,
which
enables
up
5-fold
more
sensitive
detection
oscillation
both
non-excitable
excitable
The
ratiometric
version
further
allows
super-resolution
monitoring
local
homeostasis
dynamics.
Notably,
NEMOer-f
variant
enabled
inaugural
blinks,
releasing
signals
SR
cardiomyocytes,
as
well
vivo
spontaneous
releases
zebrafish.
In
summary,
highly
sensors
expand
repertoire
allow
real-time
intricate
live
cells
high
spatiotemporal
resolution.
Frontiers in Pharmacology,
Год журнала:
2024,
Номер
15
Опубликована: Апрель 17, 2024
Cardiovascular
diseases
(CVDs)
are
currently
the
leading
cause
of
death
worldwide.
In
2022,
CVDs
contributed
to
19.8
million
deaths
globally,
accounting
for
one-third
all
global
deaths.
With
an
aging
population
and
changing
lifestyles,
pose
a
major
threat
human
health.
Mitochondria-associated
endoplasmic
reticulum
membranes
(MAMs)
communication
platforms
between
cellular
organelles
regulate
physiological
functions,
including
apoptosis,
autophagy,
programmed
necrosis.
Further
research
has
shown
that
MAMs
play
critical
role
in
pathogenesis
CVDs,
myocardial
ischemia
reperfusion
injury,
heart
failure,
pulmonary
hypertension,
coronary
atherosclerosis.
This
suggests
could
be
important
therapeutic
target
managing
CVDs.
The
goal
this
study
is
summarize
protein
complex
MAMs,
discuss
its
pathological
mechanisms
terms
functions
such
as
Ca
