Diisononyl phthalate down-regulates the expression of antioxidant genes NFE2L2 , TXN , and TXNRD2 , while Diethyl-hexyl terephthalate up-regulates their expression including SOD-1
Xenobiotica,
Journal Year:
2025,
Volume and Issue:
unknown, P. 1 - 18
Published: April 16, 2025
Phthalates,
widely
utilized
as
plasticisers
to
enhance
the
flexibility
of
rigid
materials
like
polyvinyl
chloride,
are
known
for
their
endocrine-disrupting
properties
and
cytotoxic
effects.
This
study
investigated
impact
Diisononyl
phthalate
(DINP)
Diethyl-hexyl
terephthalate
(DEHT)
on
human
endothelial
cells
(EA.hy926).
The
assessment
focused
cell
viability,
reactive
oxygen
species
(ROS)
production,
antioxidant-responsive
genes
expression
(NFE2L2,
SOD1,
TXN,
TXNRD2)
following
exposure
varying
1,
10,
100
µg/mL
DINP
or
DEHT.
Cell
viability
was
determined
using
MTT
lactate
dehydrogenase
(LDH)
release
assays.
ROS
were
measured
DCFDA
assay.
Gene
analysis
conducted
via
qRT-PCR
after
48
h
exposure.
Results
revealed
that
significantly
reduced
at
11
17%
72
h,
respectively;
whereas
increased
LDH
by
69%
48h.
levels
also
rose
19-30%,
accompanied
down-regulation
NFE2L2,
TXNRD2.
Conversely,
DEHT
had
no
adverse
effect
but
elevated
production
(11-14%)
induced
up-regulation
antioxidant
genes,
including
SOD1.
findings
indicate
could
negatively
affect
cellular
response,
leads
without
detrimental
effects
viability.
Language: Английский
The role of IGF2BP2 in macrophage-mediated NLRP3 inflammasome activation in the pathogenesis of dry AMD
Biology Direct,
Journal Year:
2025,
Volume and Issue:
20(1)
Published: April 22, 2025
Dry
age-related
macular
degeneration
(AMD)
is
a
common
chronic
degenerative
eye
disease
for
which
there
currently
no
effective
treatment.
Insulin-like
growth
factor
2
mRNA-binding
protein
(IGF2BP2)
recently
identified
m6A
reader
that
binds
RNA
and
maintains
its
stability,
thereby
participating
in
various
biological
processes.
However,
role
dry
AMD
remains
unclear.
In
this
study,
we
investigated
the
of
IGF2BP2
macrophage
NLRP3
inflammasomes
using
sodium
iodate-induced
model.
Our
results
demonstrated
highly
expressed
retinal-choroidal
tissue
induced
by
iodate,
with
effects
primarily
occurring
macrophages.
The
loss
ameliorating
AMD.
Mechanistically,
methylated
transcripts
were
subsequently
directly
recognized
specific
m
6
A
"reader",
IGF2BP2,
to
prevent
mRNA
degradation.
Furthermore,
vivo
experiments,
maintain
eye's
"immune
privilege",
employed
mesoporous
silica-based
cell
therapy
target
regulate
providing
foundation
evaluation
translation
therapies
targeting
gene.
our
study
reveals
molecular
mechanism
pathogenesis
involves
IGF2BP2-mediated
inflammasome
activation
macrophages,
highlighting
as
promising
biomarker
therapeutic
Language: Английский