Cell Reports,
Год журнала:
2019,
Номер
29(5), С. 1261 - 1273.e6
Опубликована: Окт. 1, 2019
Acute
kidney
injury
(AKI)
is
characterized
by
mitochondrial
dysfunction
and
activation
of
the
innate
immune
system.
The
cyclic
GMP-AMP
synthase
(cGAS)
stimulator
interferon
genes
(STING)
pathway
detects
cytosolic
DNA
induces
immunity.
Here,
we
investigate
role
damage
subsequent
cGAS-STING
using
a
genetically
engineered
animal
model
cisplatin-induced
AKI
cultured
tubular
cells.
Cisplatin
induced
mtDNA
leakage
into
cytosol-probably
through
BCL-2-like
protein
4
(BAX)
pores
in
outer
membrane-in
tubules,
with
pathway,
thereby
triggering
inflammation
progression,
which
improved
STING-deficient
mice.
STING
knockdown
cells
ameliorates
inflammatory
responses
cisplatin.
depletion
repletion
studies
support
via
signal
mtDNA.
Therefore,
conclude
that
mtDNA-cGAS-STING
critical
regulator
injury.
Frontiers in Cell and Developmental Biology,
Год журнала:
2021,
Номер
9
Опубликована: Март 29, 2021
Cellular
senescence
is
a
stable
cell
cycle
arrest
that
can
be
triggered
in
normal
cells
response
to
various
intrinsic
and
extrinsic
stimuli,
as
well
developmental
signals.
Senescence
considered
highly
dynamic,
multi-step
process,
during
which
the
properties
of
senescent
continuously
evolve
diversify
context
dependent
manner.
It
associated
with
multiple
cellular
molecular
changes
distinct
phenotypic
alterations,
including
proliferation
unresponsive
mitogenic
stimuli.
Senescent
remain
viable,
have
alterations
metabolic
activity
undergo
dramatic
gene
expression
develop
complex
senescence-associated
secretory
phenotype.
compromise
tissue
repair
regeneration,
thereby
contributing
toward
aging.
Removal
attenuate
age-related
dysfunction
extend
health
span.
also
act
potent
anti-tumor
mechanism,
by
preventing
potentially
cancerous
cells.
program
acts
double-edged
sword,
both
beneficial
detrimental
effects
on
organism,
an
example
evolutionary
antagonistic
pleiotropy.
Activation
p53/p21
WAF1/CIP1
p16
INK4A
/pRB
tumor
suppressor
pathways
play
central
role
regulating
senescence.
Several
other
recently
been
implicated
mediating
Herein
we
review
mechanisms
underlie
growth
particular
focus
why
stop
dividing,
stability
arrest,
hypersecretory
phenotype
how
different
are
all
integrated.
The Journal of Cell Biology,
Год журнала:
2017,
Номер
217(1), С. 65 - 77
Опубликована: Ноя. 7, 2017
Aging
is
the
major
risk
factor
for
cancer,
cardiovascular
disease,
diabetes,
and
neurodegenerative
disorders.
Although
we
are
far
from
understanding
biological
basis
of
aging,
research
suggests
that
targeting
aging
process
itself
could
ameliorate
many
age-related
pathologies.
Senescence
a
cellular
response
characterized
by
stable
growth
arrest
other
phenotypic
alterations
include
proinflammatory
secretome.
plays
roles
in
normal
development,
maintains
tissue
homeostasis,
limits
tumor
progression.
However,
senescence
has
also
been
implicated
as
cause
disease.
In
this
regard,
recent
experimental
evidence
shown
genetic
or
pharmacological
ablation
senescent
cells
extends
life
span
improves
health
span.
Here,
review
molecular
links
between
discuss
novel
therapeutic
avenues
connection
opens.
The Journal of Experimental Medicine,
Год журнала:
2018,
Номер
215(5), С. 1287 - 1299
Опубликована: Апрель 5, 2018
Detection
of
microbial
DNA
is
an
evolutionarily
conserved
mechanism
that
alerts
the
host
immune
system
to
mount
a
defense
response
infections.
However,
this
detection
also
poses
challenge
as
how
distinguish
foreign
from
abundant
self-DNA.
Cyclic
guanosine
monophosphate
(GMP)-adenosine
(AMP)
synthase
(cGAS)
sensor
triggers
innate
responses
through
production
second
messenger
cyclic
GMP-AMP
(cGAMP),
which
binds
and
activates
adaptor
protein
STING.
cGAS
can
be
activated
by
double-stranded
irrespective
sequence,
including
Although
normally
kept
inactive
in
cells
still
not
well
understood,
recent
research
has
provided
strong
evidence
genomic
damage
leads
activation
stimulate
inflammatory
responses.
This
review
summarizes
findings
on
instability
trigger
serves
link
inflammation,
cellular
senescence,
cancer.
Physiological Reviews,
Год журнала:
2019,
Номер
99(2), С. 1047 - 1078
Опубликована: Янв. 16, 2019
Cellular
senescence
is
a
permanent
state
of
cell
cycle
arrest
that
occurs
in
proliferating
cells
subjected
to
different
stresses.
Senescence
is,
therefore,
cellular
defense
mechanism
prevents
the
acquire
an
unnecessary
damage.
The
senescent
accompanied
by
failure
re-enter
response
mitogenic
stimuli,
enhanced
secretory
phenotype
and
resistance
death.
takes
place
several
tissues
during
physiological
pathological
processes
such
as
tissue
remodeling,
injury,
cancer,
aging.
Although
one
causative
aging
it
responsible
aging-related
disorders,
can
also
play
positive
role.
In
embryogenesis
are
required
for
proper
development
embryo
repair.
works
potent
barrier
prevent
tumorigenesis.
Therefore,
identification
characterization
key
features
senescence,
induction
cancer
cells,
or
elimination
pharmacological
interventions
gaining
consideration
fields
research.
Here,
we
describe
known
cell-autonomous,
noncell-autonomous
regulators
attempt
discuss
functional
role
this
fundamental
process
contexts
light
novel
therapeutic
targets.
