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:3.4.24.3 (
collagenase
)
18,340
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Glutamate excitotoxicity has been implicated in intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI). Synaptosome associated protein 23 (SNAP23) and SNAP25 are respectively participate in presynaptic glutamate release and postsynaptic glutamate receptor (NMDA receptor) trafficking, both of which are essential for glutamate-mediated excitatory toxicity. SNAP23 and SNAP25 exhibit high homology and SNAP23 has been shown to interact with
Annexin A7
(
ANXA7
). This study was to examine the role of
ANXA7
in ICH-induced neuronal damage. A
collagenase
ICH model was performed in adult male Sprague Dawley rats. First, a possible relationship between
ANXA7
and ICH pathology was confirmed by an increase in the protein and mRNA level of
ANXA7
in the brain tissue around hematoma of ICH rats and the rescue effects of
ANXA7
knockdown in vivo on neuronal death, blood-brain barrier damage, brain edema, neurobehavioral deficient, and inflammatory response. In addition, the rescue effect of
ANXA7
knockdown on neurobehavioral deficient was also verified in rat autologous blood injection ICH model. Second, we found that ICH significantly increased the phosphorylation ratio of
ANXA7
at the threonine residues mainly in neurons. Finally, based on site-specific mutagenesis, we identified that
ANXA7
phosphorylation at threonine 286 is required for its interaction with SNAP25 at presynaptic axon terminal and SNAP23 at postsynaptic axon terminal. Collectively, our findings suggest that
ANXA7
contributed to SBI at least partially through regulating glutamate toxicity after ICH. Selective inhibition of
ANXA7
phosphorylation may be a novel approach to ameliorate ICH-induced SBI.
...
PMID:Critical role for Annexin A7 in secondary brain injury mediated by its phosphorylation after experimental intracerebral hemorrhage in rats. 2919 15
High
annexin A7
expression is a potential indicator of lymphatic metastasis and poor prognosis in patients with gastric cancer (GC). The mechanism underlying the effects of
annexin A7
on GC cells remains unclear. In patients with GC, primary adenocarcinoma tissues had higher
annexin A7
expression than adjacent non-cancerous tissues (
P
< 0.05). Among three human GC cell lines with high, moderate, and low levels of differentiation, respectively, the cell line with the lowest level of differentiation displayed the highest level of
annexin A7
expression. We transfected cells of the human GC cell line BGC823 with short interfering RNAs (siRNAs) targeting
annexin A7
and investigated the effects on signaling pathways related to cancer progression by quantitative real-time PCR and western blot. The silencing of endogenous
annexin A7
suppressed the proliferation, migration, and invasion abilities of the BGC823 cells. In the cells treated with
annexin A7
siRNA, the expression of p16, p21, and p27 was significantly upregulated while that of proliferating cell nuclear antigen (PCNA), cyclin A, cyclin D1, cyclin E1, matrix metalloproteinase-2 (MMP-2), MMP-9, and intercellular cell-adhesion molecule-1 (ICAM-1) was significantly downregulated compared with that in control cells. Our results suggest that the downregulation of endogenous
annexin A7
inhibits GC cell proliferation, migration, and invasion by impacting cell cycle regulators and the expression of
MMP-1
, MMP-2, and ICAM-1. Targeting
annexin A7
may represent a valuable strategy for the diagnosis and clinical treatment of GC.
...
PMID:Downregulation of annexin A7 decreases proliferation, migration, and invasion of gastric cancer cells by reducing matrix metalloproteinase 1 and 9 expression. 3121 51
