Toxins,
Journal Year:
2024,
Volume and Issue:
16(10), P. 432 - 432
Published: Oct. 9, 2024
The
spleen
is
a
primary
target
of
deoxynivalenol
(DON)
toxicity,
but
its
underlying
molecular
mechanisms
remain
unclear.
This
study
investigates
the
effects
DON
on
inflammation,
splenic
macrophage
polarization,
endoplasmic
reticulum
(ER)
stress,
and
transcriptome
changes
(mRNA
lncRNAs)
in
mouse
spleen.
We
found
that
exposure
at
doses
2.5
or
5
mg/kg
BW
significantly
induced
inflammation
polarized
macrophages
towards
M1
phenotype.
Additionally,
activated
PERK-eIF2α-ATF4-mediated
ER
stress
upregulated
apoptosis-related
proteins
(caspase-12,
caspase-3).
inhibitor,
4-Phenylbutyric
acid,
alleviated
DON-induced
apoptosis,
polarization
macrophages.
Transcriptome
analysis
identified
1968
differentially
expressed
(DE)
lncRNAs
2664
DE
mRNAs
following
exposure.
Functional
enrichment
indicated
genes
were
involved
pathways
associated
with
immunity,
including
Th17
cell
differentiation,
TNF
signaling,
IL-17
while
downregulated
linked
to
survival
growth
pathways.
Furthermore,
370
predicted
255
immune
processes,
innate
response,
interferon-beta
cytokine
production
regulation,
leukocyte
NF-κB
signaling
genes.
provides
new
insights
into
toxicity
system.
Research Square (Research Square),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 14, 2024
Abstract
Iron
overload
and
ferroptosis
are
associated
with
intestinal
ischemia
reperfusion
(II/R)-induced
acute
lung
injury
(ALI).
However,
the
mechanisms
underlying
regulation
of
iron
homeostasis
remain
unclear.
Nrf2
regulates
cellular
homeostasis;
however,
its
impact
on
ALI
pathology
mechanism
action
requires
further
investigation.
Ubiquitin
ligase
E3B
(UBE3B)
plays
a
critical
role
in
proteasome
pathway,
which
is
essential
for
protein
turnover
ubiquitin-mediated
signaling.
A
recent
study
found
that
UBE3B
oxidative
stress;
it
remains
unknown
whether
related
to
Nrf2.
Furthermore,
exact
largely
uncharacterized.
In
present
study,
immunohistochemical
analysis
expression
type
II
alveolar
epithelial
cells
(AECII)
was
conducted
be
increased
II/R-ALI.
Western
blot
indicated
hyperactivation
may
alleviate
stress,
thereby
protecting
against
ALI.
Moreover,
involved
metabolism
dysfunction
ferroptosis.
deficiency
enhanced
process
nuclear
receptor
coactivator
4
(NCOA4)-mediated
ferritinophagy
ferrous
ion
content,
whereas
overexpression
reversed
harmful
effects
knockdown
AECⅡ,
promote
AECⅡ
This
highlights
Nrf2/UBE3B/NCOA4
axis
II/R-ALI
pathogenesis,
suggesting
activation
promising
strategy
treatment.
