Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.4.1.2 (
glutamate dehydrogenase
)
4,380
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
A rat HIRI model was constructed and treated with an intraperitoneal injection of agomir-
miR-494
or agomir-NC (negative control) for 7 days after the surgery. The pathophysiological changes in sham-operated rats, HIRI, HIRI + agomir-
miR-494
, and HIRI + agomir-NC were compared. The effect of
miR-494
was also assessed in an H
2
O
2
-induced apoptosis model. Hepatic AML12 cells were transfected with mimics NC or
miR-494
mimics, followed by 6-h H
2
O
2
treatment. Cell proliferation and apoptosis were detected by CCK8 assay and flow cytometry, respectively. Further, the
miR-494
target gene was identified by luciferase reporter assay, and verified both
in vitro
and
in vivo
experiments. The activity of AKT pathway was further analyzed
in vivo
by Western blot. HIRI + agomir-
miR-494
rats exhibited significantly higher
miR-494
expression, lower serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and
glutamate dehydrogenase
(GLDH) level, lower hepatic MDA, TOA, and OSI, alleviated hepatic necrosis, reduced hepatocyte apoptosis, and decreased expression of apoptosis-related proteins, when compared with HIRI + agomir-NC rats (
P
<0.05 or 0.01). After H
2
O
2
treatment,
AML
-12 cells transfected with
miR-494
mimics had significantly higher proliferation and lower apoptosis rate compared with mimics NC group (
P
<0.01). PTEN was identified as an
miR-494
target gene. PTEN expression was significantly down-regulated in AML12 cells transfected with
miR-494
mimics, and was up-regulated by treatment of
miR-494
inhibitor (
P
<0.01). Moreover, HIRI + agomir-
miR-494
rats exhibited significantly lower PTEN expression, and higher p-AKT, p-mTOR, and p-p70S6K levels compared with HIRI + agomir-NC rats. Therefore,
miR-494
protected rats against hepatic ischemia/reperfusion (I/R) injury through down-regulating its downstream target gene
PTEN
, leading to the activation of PI3K/AKT signaling pathway.
...
PMID:
miR-494
up-regulates the PI3K/Akt pathway via targetting PTEN and attenuates hepatic ischemia/reperfusion injury in a rat model. 2884 16
