Current Issues in Molecular Biology,
Год журнала:
2023,
Номер
45(5), С. 3848 - 3876
Опубликована: Май 2, 2023
As
evolutionarily
conserved
signaling
cascades,
AhR
and
Wnt
pathways
play
a
critical
role
in
the
control
over
numerous
vital
embryonic
somatic
processes.
performs
many
endogenous
functions
by
integrating
its
pathway
into
organ
homeostasis
maintenance
of
crucial
cellular
biological
The
regulates
cell
proliferation,
differentiation,
other
phenomena,
this
regulation
is
important
for
development
dynamic
balance
adult
tissues.
are
main
participating
fate
function.
They
occupy
central
position
variety
processes
linked
with
various
pathological
conditions.
Given
importance
these
two
it
would
be
interesting
to
elucidate
implications
their
interaction.
Functional
connections
between
signals
take
place
cases
crosstalk
or
interplay,
about
which
quite
lot
information
has
been
accumulated
recent
years.
This
review
focused
on
studies
mutual
interactions
key
mediators
Wnt/β-catenin
assessment
complexity
cascade
canonical
pathway.
Biochemical Pharmacology,
Год журнала:
2023,
Номер
216, С. 115801 - 115801
Опубликована: Сен. 9, 2023
Air
pollution
is
the
leading
cause
of
lung
cancer
after
tobacco
smoking,
contributing
to
20%
all
deaths.
Increased
risk
associated
with
living
near
trafficked
roads,
occupational
exposure
diesel
exhaust,
indoor
coal
combustion
and
cigarette
suggest
that
components
in
ambient
fine
particulate
matter
(PM2.5),
such
as
polycyclic
aromatic
hydrocarbons
(PAHs),
may
be
central
drivers
cancer.
Activation
aryl
hydrocarbon
receptor
(AhR)
induces
expression
xenobiotic-metabolizing
enzymes
(XMEs)
increase
PAH
metabolism,
formation
reactive
metabolites,
oxidative
stress,
DNA
damage
mutagenesis.
Lung
tissues
from
smokers
workers
exposed
high
PM
levels
contain
mutagenic
signatures
derived
PAHs.
However,
recent
findings
air
PM2.5
primarily
development
through
tumor
promotion
cells
harboring
naturally
acquired
oncogenic
mutations,
thus
lacking
typical
PAH-induced
mutations.
On
this
background,
we
discuss
role
AhR
PAHs
caused
by
focusing
on
promoting
properties
including
immune
system,
cell
proliferation
survival,
microenvironment,
cell-to-cell
communication,
growth
metastasis.
We
dichotomy
patterns
observed
between
smoking
outdoor
represent
two
ends
a
dose–response
continuum
exposure,
where
peripheral
appears
driving
factor
at
relatively
low-dose
exposures
PM2.5,
whereas
genotoxicity
airways
becomes
increasingly
more
important
higher
encountered
exposure.
Environment International,
Год журнала:
2024,
Номер
190, С. 108889 - 108889
Опубликована: Июль 18, 2024
Air
pollution
is
one
of
the
most
severe
environmental
health
hazards,
and
airborne
nanoparticles
(diameter
<100
nm)
are
considered
particularly
hazardous
to
human
health.
They
produced
by
various
sources
such
as
internal
combustion
engines,
wood
biomass
burning,
fuel
natural
gas
combustion,
their
origin,
among
other
parameters,
determines
intrinsic
toxicity
for
reasons
that
not
yet
fully
understood.
Many
constituents
toxic
or
at
least
hazardous,
including
polycyclic
aromatic
hydrocarbons
(PAHs)
heavy
metal
compounds,
in
addition
gaseous
pollutants
present
aerosol
fraction,
NOx,
SO2,
ozone.
All
these
compounds
can
cause
oxidative
stress,
mitochondrial
damage,
inflammation
lungs
tissues,
cellular
organelles.
Epidemiological
investigations
concluded
may
affect
respiratory,
cardiovascular,
nervous
systems.
Moreover,
particulate
matter
has
been
linked
an
increased
risk
lung
cancer,
a
carcinogenic
effect
related
DNA
but
inflammatory
response
pollutants,
which
release
cytokines
promotes
proliferation
pre-existing
mutated
cancer
cells.
The
mechanisms
behind
be
investigated
experimentally
using
cell
cultures
animal
models.
Methods
gathering
have
explored,
standardized
protocols
needed
ensure
samples
accurately
represent
chemical
mixtures
environment.
Toxic
studied
models,
designing
realistic
exposure
settings
challenging.
air–liquid
interface
(ALI)
system
directly
exposes
cells,
mimicking
particle
inhalation
into
lungs.
Continuous
research
monitoring
essential
understanding
effects
developing
active
strategies
mitigate
risks
Ecotoxicology and Environmental Safety,
Год журнала:
2024,
Номер
278, С. 116429 - 116429
Опубликована: Май 7, 2024
Air
pollutants
deteriorate
the
survival
environment
and
endanger
human
health
around
world.
A
large
number
of
studies
have
confirmed
that
air
pollution
jeopardizes
multiple
organs,
such
as
cardiovascular,
respiratory,
central
nervous
systems.
Skin
is
largest
organ
first
barrier
protects
us
from
outside
particulate
matter
(PM),
polycyclic
aromatic
hydrocarbons
(PAHs),
volatile
organic
compounds
(VOCs)
will
affect
structure
function
skin
bring
about
development
inflammatory
diseases
(atopic
dermatitis
(AD),
psoriasis),
accessory
(acne,
alopecia),
auto-immune
(cutaneous
lupus
erythematosus(CLE)
scleroderma),
even
tumors
(melanoma,
basal
cell
carcinoma
(BCC),
squamous-cell
(SCC)).
Oxidative
stress,
damage,
microbiome
dysbiosis,
inflammation
are
pathogenesis
stimulation.
In
this
review,
we
summarize
current
evidence
on
effects
possible
mechanisms
to
provide
strategies
for
future
research.
Nature Communications,
Год журнала:
2025,
Номер
16(1)
Опубликована: Фев. 3, 2025
The
aryl
hydrocarbon
receptor
(AHR)
possesses
an
extraordinary
capacity
to
sense
and
respond
a
wide
range
of
small-molecule
ligands,
ranging
from
polycyclic
aromatic
hydrocarbons
endogenous
compounds.
Upon
ligand
binding,
AHR
translocates
the
cytoplasm
nucleus,
forming
transcriptionally
active
complex
with
nuclear
translocator
(ARNT),
for
DNA
binding
initiation
gene
expression
programs
that
include
cellular
detoxification
pathways
immune
responses.
Here,
we
examine
molecular
mechanisms
governing
AHR's
high-affinity
activation
by
diverse
group
ligands.
Crystal
structures
AHR-ARNT-DNA
complexes,
bound
each
six
established
including
Tapinarof,
6-formylindolo[3,2-b]carbazole
(FICZ),
benzo[a]pyrene
(BaP),
β-naphthoflavone
(BNF),
Indigo
Indirubin,
reveal
unconventional
mode
subunit
assembly
intimate
association
between
PAS-B
domains
ARNT.
domain
utilizes
eight
conserved
residues
whose
dynamic
rearrangements
account
ability
bind
ligands
through
hydrophobic
π-π
interactions.
Our
findings
further
structural
underpinnings
ligand-driven
mechanism,
whereby
segment
protein
undergoes
transition
chaperone
engagement
ARNT
heterodimer
stabilization,
generate
competent
assembly.
results
provide
key
information
future
development
AHR-targeting
drugs.
Biochemical Pharmacology,
Год журнала:
2023,
Номер
216, С. 115798 - 115798
Опубликована: Сен. 9, 2023
The
aryl
hydrocarbon
receptor
(AHR)
signaling
pathway
is
a
complex
regulatory
network
that
plays
critical
role
in
various
biological
processes,
including
cellular
metabolism,
development,
and
immune
responses.
complexity
of
AHR
arises
from
multiple
factors,
the
diverse
ligands
activate
receptor,
expression
level
itself,
its
interaction
with
nuclear
translocator
(ARNT).
Additionally,
crosstalks
repressor
(AHRR)
or
other
transcription
factors
pathways
it
can
also
mediate
non-genomic
effects.
Finally,
posttranslational
modifications
partners,
epigenetic
regulation
target
genes,
as
well
AHR-mediated
induction
enzymes
degrade
AHR-activating
may
contribute
to
context-specificity
activation.
Understanding
crucial
for
deciphering
physiological
pathological
roles
developing
therapeutic
strategies
targeting
this
pathway.
Ongoing
research
continues
unravel
intricacies
signaling,
shedding
light
on
mechanisms
controlling
functions.
In
addition
to
the
high
neurotoxicity,
depression,
and
anxiety
are
most
prominent
characteristics
of
methamphetamine
(Meth)
withdrawal.
Studies
date
on
issue
Meth-associated
depression
focused
brain,
however,
whether
peripheral
homeostasis,
especially
"microbiota-gut"
axis
participates
in
these
adverse
outcomes,
remains
poorly
understood.
current
study,
with
fecal
microbiota
transplantation
(FMT)
assay,
mice
received
from
Meth
withdrawal
displayed
marked
behaviors.
The
16S
rRNA
sequencing
results
showed
that
contributed
a
striking
reduction
Akkermansia,
Bacteroides,
Faecalibaculum,
Desulfovibrio,
Anaerostipes,
which
known
be
associated
tryptophan
(TRP)
metabolism.
Noteworthily,
substantial
decreases
indole
derivatives
TRP
metabolic
pathway,
including
IAA,
IPA,
ILA,
IET,
IArA,
IAld,
TRM
were
observed
serum
both
abusing
humans
during
UHPLC-MS/MS
analysis.
Combining
low
diet
mouse
model,
obviously
impeded
behaviors,
further
strengthened
by
evidence
administration
dramatically
ameliorated
induced
aberrant
Importantly,
protective
effects
remarkably
counteracted
aryl
hydrocarbon
receptor
knockout
(AhR
KO)
mice,
underlining
key
roles
microbiota-indoles-AhR
signaling
anxiety.
Collectively,
important
contribution
present
work
is
we
provide
first
gut
homeostasis
disturbance
but
not
limited
plays
role
driving
Meth-induced
periods
withdrawal,
disturbance.
Therefore,
targeting
AhR
may
novel
insight
into
therapeutic
strategies
for
psychological
disorders.
Cell Biochemistry and Function,
Год журнала:
2025,
Номер
43(2)
Опубликована: Янв. 27, 2025
ABSTRACT
The
aryl
hydrocarbon
receptor
(AhR),
a
ligand‐activated
transcription
factor,
is
extensively
expressed
in
diverse
human
organs
and
plays
pivotal
role
mediating
the
onset,
progression,
severity
of
numerous
diseases.
Recent
research
has
explored
substantial
impact
AhR
on
skin
homeostasis
related
pathologies.
As
multi‐layered
organ,
comprises
multiple
cell
populations
that
express
AhR.
In
this
review,
we
introduce
various
cells
its
barrier
function.
Furthermore,
explore
involvement
development
diseases,
highlighting
potential
as
therapeutic
target
for
disorders.
By
targeting
AhR,
may
open
new
avenues
novel
efficient
disease
treatments.