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: UNIPROT:P17174 (
aspartate aminotransferase
)
14,872
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Vinclozolin and procymidone are antiandrogens that are thought to share a common androgen receptor (AR) mediated mechanism of action. This assessment is based primarily on morphological, AR binding, and in vitro transcriptional activation studies. Studies designed to evaluate the gene expression profiles induced by these compounds have the potential to provide further information to test this hypothesis. We have used targeted gene arrays to examine gene expression in the ventral prostate (VP) of 100-day old Sprague Dawley male rats exposed to either vinclozolin or procymidone. Animals were castrated and administered silastic implants with or without testosterone. A subset of testosterone treated animals was then dosed with 200 mg/kg of either fungicide in corn oil. Four treatment groups were used: castrated (C), testosterone (T), testosterone+vinclozolin (V), and testosterone+procymidone (P). Tissue from the VP was collected from six animals per group (3 animals per block x 2 blocks) at 20 h and at 4 days after the start of treatment. Total RNA was then isolated and gene expression analyzed using Clontech Atlas Rat 1.2 Toxicology arrays. When compared to group T, similar changes in gene expression were observed in groups C, P and V at both the 20 h and 4 day time points. After 20 h of treatment, 20 genes were similarly affected across these three treatment groups. Down-regulated genes included various molecular chaperones, the 11-kDa diazepam binding inhibitor, cyclin D1, and mitochondrial
aspartate aminotransferase
. Genes such as the androgen receptor,
PTEN
, and ERK2 were up-regulated. Three of the down-regulated genes, GRP78 (BiP), Dad1, and mitochondrial
aspartate aminotransferase
have been previously shown to be directly androgen regulated. Fifty-four genes were affected at 20 h, whereas, 311 genes were altered 4 days after the start of treatment. These observations, in part, may reflect regression of the VP at the later time point. These results support the hypothesis that procymidone and vinclozolin share a common mechanism or mode of action, a critical step in a cumulative risk assessment.
...
PMID:Gene expression analysis in the ventral prostate of rats exposed to vinclozolin or procymidone. 1568 71
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
Circular RNAs (circRNAs) have been shown to play critical roles in cancer biology, but their functions in nonalcoholic steatohepatitis (NASH) remain unexplored. Full length of circRNA_002581 was amplified and sequenced, followed by RNA immunoprecipitation, RNA-Fluorescence in Situ Hybridization and dual luciferase reporter gene analysis to confirm the existence of the circRNA_002581-miR-122-CPEB1 regulatory axis in vitro. CircRNA_002581 knockdown was used to study its roles in high concentration of free fatty acids-induced NASH-like cell model and a methionine and choline deficiency (MCD) diet-induced NASH mice model. Autophagy flux and related potential
PTEN
-AMPK-mTOR pathway were tested by western blot. CircRNA_002581 overexpression significantly relieved the inhibitory role of miR-122 on its target CPEB1 by sponging miR-122. CircRNA_002581 knockdown markedly attenuated lipid droplet accumulation, reduced the levels of alanine aminotransferase (ALT),
aspartate aminotransferase
(
AST
), pro-inflammatory cytokines, apoptosis, H
2
O
2
, and increased ATP level in both mice and cellular models of NASH. Mechanistically, circRNA_002581 interference significantly rescue the defective autophagy evidenced by increased autophagosome number, upregulated LC3-II/I level, and decreased p62 level. Further chloroquine-mediated total autophagy inhibition antagonizes the protective effect of circRNA_002581 knockdown. Finally, CPEB1-
PTEN
-AMPK-mTOR pathway is shown to link the autophagy and circRNA_002581 knockdown-mediated NASH alleviation. CircRNA_002581-miR-122-CPEB1 axis actively participates in the pathogenesis of NASH through
PTEN
-AMPK-mTOR pathway-related autophagy suppression. Targeting circRNA_002581 is a potential therapeutic strategy for NASH through partial autophagy restoration.
...
PMID:Antagonizing circRNA_002581-miR-122-CPEB1 axis alleviates NASH through restoring PTEN-AMPK-mTOR pathway regulated autophagy. 3205 40
