Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.108 (TAT)
 2,389 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exocytosis of endothelial granules promotes thrombosis and inflammation and may contribute to the pathophysiology of early reperfusion injury following myocardial ischemia. TAT-NSF700 is a novel peptide that reduces endothelial exocytosis by inhibiting the ATPase activity and disassembly activity of N-ethylmaleimide-sensitive factor (NSF), a critical component of the exocytic machinery. We hypothesized that TAT-NSF700 would limit myocardial injury in an in vivo murine model of myocardial ischemia/reperfusion injury. Mice were subjected to 30 minutes of ischemia followed by 24 hours of reperfusion. TAT-NSF700 or the scrambled control peptide TAT-NSF700scr was administered intravenously 20 minutes before the onset of ischemia. Myocardial ischemia/reperfusion caused endothelial exocytosis, myocardial infarction, and left ventricular dysfunction. However, TAT-NSF700 decreased von Willebrand factor levels after myocardial ischemia/reperfusion, attenuated myocardial infarct size by 47%, and preserved left ventricular structure and function. These data suggest that drugs targeting endothelial exocytosis may be useful in the treatment of myocardial injury following ischemia/reperfusion.
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PMID:Inhibition of N-ethylmaleimide-sensitive factor protects against myocardial ischemia/reperfusion injury. 1793 25

Long-term memory formation is believed to involve alterations of synaptic efficacy. It has been shown that GluR1-containing AMPA receptors are inserted into synapses following stimuli leading to plasticity and that GluR2/GluR3-containing receptors replace existing synaptic AMPA receptors continuously and may act to maintain synaptic efficacy. Maintaining GluR2/GluR3 receptors level in synapse requires interactions of N-ethylmaleimide-sensitive factor (NSF) with GluR2. To assess possible roles of NSF-GluR2 interaction in rat lateral amygdala (LA) in fear memory formation we used a specific GluR2-NSF interaction inhibitory peptide (pep-R845A). This inhibitory peptide, composed of a modified NSF binding site of GluR2, was previously shown to interact specifically with NSF and to affect AMPA-mediated synaptic efficacy. The inhibitory peptide was linked to a TAT peptide (TAT-pep-R845A) to facilitate internalization into LA cells. Infusion of the TAT-pep-R845A inhibitory peptide into LA 30 min before fear conditioning led to a significant impairment of long-term fear memory formation. In contrast, the control TAT peptide alone had no effect on fear memory. Injection of TAT-pep-R845A peptide into LA had no effect on short-term fear memory. In addition, the inhibitory peptide had no effect on memory retrieval when injected into LA 30 min before fear memory test. Furthermore, maintenance of memory was not impaired when the peptide was injected 24 h after fear conditioning and fear memory was tested 48 h afterward. These results show that GluR2-NSF interaction in LA is necessary for fear memory consolidation but not retrieval or persistence.
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PMID:Interaction between N-ethylmaleimide-sensitive factor and GluR2 is essential for fear memory formation in lateral amygdala. 2110 36

Many studies have reported a withdrawal-dependent increase in synaptic AMPA receptor (AMPAR) levels in the nucleus accumbens (NAc) of cocaine-sensitized rats; however, the exact relationship between the expression of sensitization and altered AMPAR surface expression in the NAc has not yet been investigated. We demonstrated that the expression of behavioral sensitization was negatively controlled by N-ethylmaleimide-sensitive factor (NSF)-GluR2 interactions in the NAc. The upregulation of NSF-GluR2 interactions, which may be resulted by the increase in NSF S-nitrosylation after withdrawal from cocaine, was associated with the changes in the expression of behavioral sensitization. Disruption of NSF-GluR2 interactions in the NAc with a specific peptide, TAT-pep-R845A, increased the locomotor response of rats to cocaine by decreasing GluR2 surface insertion. In contrast, prevention of GluR2-containing AMPARs removal from synapses with Pep2-EVKI attenuated the expression of behavioral sensitization. Similarly, treatment with the nitric oxide donor, S-Nitroso-N-acetyl-DL-penicillamine (SNAP), attenuated the expression of locomotor sensitization by promoting GluR2 surface expression. This effect was mediated by the binding of S-nitrosylated NSF to GluR2, which promoted the surface expression of AMPARs. Noticeably, exogenous injection of SNAP into NAc also attenuated the expression of cocaine-induced conditioned place preference. Thus, these results indicate that increased NSF-GluR2 interactions in the NAc after withdrawal from cocaine attenuated the expression of behavioral sensitization and serves as a negative regulatory mechanism in drug-exposed individuals.
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PMID:Interactions between N-ethylmaleimide-sensitive factor and GluR2 in the nucleus accumbens contribute to the expression of locomotor sensitization to cocaine. 2459 50