Validation studies and multi-omics analysis of Zhx2 as a candidate quantitative trait gene underlying brain oxycodone metabolite (oxymorphone) levels and behavior
Journal of Pharmacology and Experimental Therapeutics,
Год журнала:
2025,
Номер
unknown, С. 103557 - 103557
Опубликована: Март 1, 2025
Sensitivity
to
the
subjective
reinforcing
properties
of
opioids
has
a
genetic
component
and
can
predict
addiction
liability
opioid
compounds.
We
previously
identified
Zhx2
as
candidate
gene
underlying
increased
brain
concentration
oxycodone
(OXY)
metabolite
oxymorphone
(OMOR)
in
BALB/cJ
(J)
versus
BALB/cByJ
(By)
females
that
could
increase
OXY
state-dependent
reward.
A
large
structural
intronic
variant
is
associated
with
robust
reduction
expression
J
mice,
which
we
hypothesized
enhances
OMOR
levels
addiction-like
behaviors.
tested
this
hypothesis
by
restoring
loss-of-function
mice
(mouse
endogenous
retroviral
element
knockout)
modeling
through
knocking
out
coding
exon
(exon
3
knockout
[E3KO])
By
assessing
behavior.
Consistent
our
hypothesis,
E3KO
showed
an
OXY-induced
locomotor
activity.
However,
contrary
conditioned
place
preference
decreased
males.
also
overexpressed
livers
brains
observed
overexpression
select
regions
was
reduced
learning.
Integrative
transcriptomic
proteomic
analysis
astrocyte
function,
cell
adhesion,
extracellular
matrix
properties,
endothelial
functions
pathways
influencing
These
results
support
quantitative
trait
changes
behavior
implicate
potential
mechanisms
together
inform
overall
understanding
function.
SIGNIFICANCE
STATEMENT:
This
study
validated
whose
dysfunction
increases
highly
potent
addictive
oxycodone,
oxymorphone,
female-specific
manner.
result
broad
implications
for
role
metabolism
(the
active
ingredient
OxyContin)
highlights
need
sex
differences
it
relates
use
disorder.
Язык: Английский
Alterations in phosphatidylethanolamine metabolism impacts hepatocellular lipid storage, energy homeostasis, and proliferation
Courtney M Holdaway,
Kelly‐Ann Leonard,
Randal C. Nelson
и другие.
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids,
Год журнала:
2025,
Номер
unknown, С. 159608 - 159608
Опубликована: Март 1, 2025
Язык: Английский
The emerging role of ethanolamine phosphate phospholyase in regulating hepatic phosphatidylethanolamine and plasma lipoprotein metabolism in mice
The FASEB Journal,
Год журнала:
2024,
Номер
38(18)
Опубликована: Сен. 23, 2024
Ethanolamine
phosphate
phospholyase
(ETNPPL)
is
an
enzyme
that
irreversibly
degrades
phospho-ethanolamine
(p-ETN),
intermediate
in
the
Kennedy
pathway
of
phosphatidylethanolamine
(PE)
biosynthesis.
PE
second
most
abundant
phospholipid
mammalian
membranes.
Disturbance
hepatic
homeostasis
has
been
linked
to
development
metabolic
dysfunction-associated
steatotic
liver
disease
(MASLD).
We
generated
whole-body
Etnppl
knockout
mice
investigate
impact
genetic
deletion
on
lipid
metabolism.
Primary
hepatocytes
isolated
from
Язык: Английский
Differential Gene Expression Analysis Supports Dysregulation of Mitochondrial Activity as a New Perspective for Glioblastoma's Aggressiveness
SSRN Electronic Journal,
Год журнала:
2024,
Номер
unknown
Опубликована: Янв. 1, 2024
Brain
cancer
is
considered
one
of
the
most
aggressive
and
lethal
types
cancer,
including
primary
tumors,
subdivided
into
milder
forms
such
as
low-grade
gliomas
glioblastoma,
form
with
metastasis.
Among
hallmarks
deregulation
mitochondrial
metabolism
has
not
yet
been
fully
elucidated.
Therefore,
search
for
biomarkers
that
can
be
used
indicators
progression
this
type
necessary.
The
aim
study
was
to
investigate
difference
in
gene
expression
between
astrocytoma-type
glioblastomas,
how
genes
involved
influence
proliferative
cascade
associated
tumor
invasion.
From
differential
analysis
glioblastoma
when
compared
form,
11
differentially
expressed
were
found
our
study,
six
which
upregulated
(ATP5MGL,
C15orf48,
MCUB,
TERT,
AGXT
CYP27B1)
four
downregulated
(SLC2A4,
GK2,
SLC25A48,
ETNPPL
HMGCS2).
these
genes,
we
highlight
none
them
had
reported
until
research,
suggest
possible
biomarkers,
since
they
are
essential
pathways
tumor,
glucose
metabolization,
gluconeogenesis,
calcium
vitamin
D
metabolism,
activation
metastatic
cascade.
Язык: Английский
Differential Gene Expression Analysis Supports Dysregulation of Mitochondrial Activity as a New Perspective for Glioblastoma's Aggressiveness
Опубликована: Янв. 1, 2024
Brain
cancer
is
considered
one
of
the
most
aggressive
and
lethal
types
cancer,
including
primary
tumors,
subdivided
into
milder
forms
such
as
low-grade
gliomas
glioblastoma,
form
with
metastasis.
Among
hallmarks
deregulation
mitochondrial
metabolism
has
not
yet
been
fully
elucidated.
Therefore,
search
for
biomarkers
that
can
be
used
indicators
progression
this
type
necessary.
The
aim
study
was
to
investigate
difference
in
gene
expression
between
astrocytoma-type
glioblastomas,
how
genes
involved
influence
proliferative
cascade
associated
tumor
invasion.
From
differential
analysis
glioblastoma
when
compared
form,
11
differentially
expressed
were
found
our
study,
six
which
upregulated
(ATP5MGL,
C15orf48,
MCUB,
TERT,
AGXT
CYP27B1)
four
downregulated
(SLC2A4,
GK2,
SLC25A48,
ETNPPL
HMGCS2).
these
genes,
we
highlight
none
them
had
reported
until
research,
suggest
possible
biomarkers,
since
they
are
essential
pathways
tumor,
glucose
metabolization,
gluconeogenesis,
calcium
vitamin
D
metabolism,
activation
metastatic
cascade.
Язык: Английский
Validation studies and multi-omics analysis of Zhx2 as a candidate quantitative trait gene underlying brain oxycodone metabolite (oxymorphone) levels and behavior
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 1, 2024
ABSTRACT
Sensitivity
to
the
subjective
reinforcing
properties
of
opioids
has
a
genetic
component
and
can
predict
addiction
liability
opioid
compounds.
We
previously
identified
Zhx2
as
candidate
gene
underlying
increased
brain
concentration
oxycodone
(
OXY
)
metabolite
oxymorphone
OMOR
in
BALB/cJ
J
versus
BALB/cByJ
By
females
that
could
increase
state-dependent
reward.
A
large
structural
intronic
variant
is
associated
with
robust
reduction
expression
mice,
which
we
hypothesized
enhances
levels
addiction-like
behaviors.
tested
this
hypothesis
by
restoring
loss-of-function
Js
MVKO
modeling
through
knocking
out
coding
exon
E3KO
Bys
assessing
behavior.
Consistent
our
hypothesis,
showed
an
OXY-induced
locomotor
activity.
However,
contrary
OXY-CPP
was
decreased
males.
also
overexpressed
livers
brains
observed
overexpression
select
regions
reduced
learning.
Integrative
transcriptomic
proteomic
analysis
mice
astrocyte
function,
cell
adhesion,
extracellular
matrix
properties,
endothelial
functions
pathways
influencing
These
results
support
quantitative
trait
changes
behavior
implicate
potential
mechanisms
together
inform
overall
understanding
function.
Язык: Английский
Differential gene expression analysis supports dysregulation of mitochondrial activity as a new perspective for glioblastoma’s aggressiveness
Heliyon,
Год журнала:
2024,
Номер
10(22), С. e40414 - e40414
Опубликована: Ноя. 1, 2024
Brain
cancer
is
considered
one
of
the
most
aggressive
and
lethal
types
cancer,
including
primary
tumors,
being
subdivided
into
milder
forms
such
as
low-grade
gliomas
glioblastoma,
form
with
higher
invasion.
Among
hallmarks
deregulation
mitochondrial
metabolism
has
not
yet
been
fully
elucidated.
Therefore,
search
for
biomarkers
that
can
be
used
indicators
progression
this
type
necessary.
The
aim
study
was
to
investigate
difference
in
gene
expression
between
astrocytoma-type
glioblastomas,
how
genes
involved
influence
proliferative
cascade
associated
tumor
From
differential
analysis
glioblastoma
when
compared
form,
11
differentially
expressed
(DEGs)
were
found
our
study,
six
which
upregulated
(ATP5MGL,
C15orf48,
MCUB,
TERT,
AGXT
CYP27B1)
four
downregulated
(SLC2A4,
GK2,
SLC25A48,
ETNPPL
HMGCS2).
To
validate
findings,
we
other
independent
bulk
RNA-seq
datasets
evaluated
number
normalized
counts
DEGs
founded.
these
genes,
highlight
none
them
had
reported
until
research,
suggest
possible
further
explored,
since
they
are
essential
pathways
tumor,
glucose
metabolization,
gluconeogenesis,
calcium
vitamin
D
metabolism,
activation
invasion
cascade.
Язык: Английский
Efeitos das interações farmacológicas do composto 2 - amino etil dihidrogeno fosfato (2-AEH2F) em linhagens tumorais de glioblastoma humano
Опубликована: Сен. 14, 2023
interações
farmacológicas
do
2
aminoetil
dihidrogeno
fosfato
em
linhagens
tumorais
de
Gliobastoma
humano
",
protocolado
sob
o
CEUAx
nº
8463260521,