Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The acute neurotoxicity and effects upon cholinergic axons of an intracerebrally injected synthetic peptide corresponding to the first 1-40 amino acids of beta-amyloid protein (beta AP1-40) was studied in rats. A synthetic peptide with the reverse sequence (beta AP40-1) or the vehicle alone were injected in the contralateral hemisphere as control. The size of the resulting lesions was quantified in serial sections using an image analyzer. Counts of cholinergic and noradrenergic fibers were also obtained around the lesion area. The results revealed that beta AP1-40 was significantly more toxic than both reverse peptide and the vehicle. The latter two, however, also caused considerable neurotoxicity. beta AP1-40 was toxic to both cholinergic and noradrenergic fibers to the same extent, and this toxicity was limited to the immediate vicinity of the lesion. This study confirms and extends the results of previous studies reporting neurotoxic effects of intracerebrally injected beta-amyloid in the rat. Our results also show that beta AP1-40 itself is not the source of the altered acetylcholinesterase enzyme activity that has been described in the plaques and tangles of Alzheimer's disease.
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PMID:The acute neurotoxicity and effects upon cholinergic axons of intracerebrally injected beta-amyloid in the rat brain. 146 43

The 5' region of the acetylcholinesterase gene from the electric ray Torpedo californica has been cloned and its cap site identified. The 5' untranslated region is divided into two exons where a small exon extending between bp -22 to -60 is alternatively spliced. Cap sites are defined at two positions, bp -138 and -143. Twenty-one base pairs 5' of the -143 cap site a repeating TATA sequence is found. Further upstream in the gene consensus sequences for Sp1, AP1, and AP2 factors are evident. The promoter region of the acetylcholinesterase gene enhances transcription of a luciferase reporter gene transfected into C2 myoblasts. However, increased transcription was not evident after C2 myoblasts were induced to form myotubes. Cotransfection of this construct with c-Jun (AP1) and AP2 expression vectors shows marked increases of transcription rates in HepG2 and C2 cells. Protein kinase A elicited regulation of expression is also evident in quail fibroblasts. In gel retardation experiments both recombinant c-Jun (AP1) and AP2 proteins bind to the appropriate Torpedo sequences. Cellular extracts from the Torpedo electric organ exhibit AP2 binding activity. Thus, although all facets of specific regulation expected upon differentiation of mammalian muscle cells were not evident, the 5'-flanking region from the Torpedo AChE gene contains consensus sequences and functional promoter elements typical of mammalian nerve and muscle systems.
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PMID:Promoter elements and transcriptional regulation of the acetylcholinesterase gene. 842 73

Eosinophils are observed to localize to cholinergic nerves in a variety of inflammatory conditions such as asthma, rhinitis, eosinophilic gastroenteritis, and inflammatory bowel disease, where they are also responsible for the induction of cell signaling. We hypothesized that a consequence of eosinophil localization to cholinergic nerves would involve a neural remodeling process. Eosinophil co-culture with cholinergic IMR32 cells led to increased expression of the M2 muscarinic receptor, with this induction being mediated via an adhesion-dependent release of eosinophil proteins, including major basic protein and nerve growth factor. Studies on the promoter sequence of the M2 receptor indicated that this induction was initiated at a transcription start site 145 kb upstream of the gene-coding region. This promoter site contains binding sites for a variety of transcription factors including SP1, AP1, and AP2. Eosinophils also induced the expression of several cholinergic genes involved in the synthesis, storage, and metabolism of acetylcholine, including the enzymes choline acetyltransferase, vesicular acetylcholine transferase, and acetylcholinesterase. The observed eosinophil-induced changes in enzyme content were associated with a reduction in intracellular neural acetylcholine but an increase in choline content, suggesting increased acetylcholine turnover and a reduction in acetylcholinesterase activity, in turn suggesting reduced catabolism of acetylcholine. Together these data suggest that eosinophil localization to cholinergic nerves induces neural remodeling, promoting a cholinergic phenotype.
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PMID:Eosinophil-mediated cholinergic nerve remodeling. 1645 88

We show that H2O2 increases acetylcholinesterase (AChE) expression via transcriptional activation through c-Jun N-terminal kinase (JNK), since the JNK inhibitor SP600125, but not the extracellular signal-regulated kinase (ERK) pathway inhibitor PD98059 or p38 kinase inhibitor SB203580, attenuated H2O2-induced AChE expression and its promoter activity. Overexpression of hemagglutinin (HA)-JNK increases H2O2-induced AChE expression and its promoter activity, whereas the dominant negative mutant form of JNK suppressed H2O2-induced AChE expression and promoter activity. Mutation analysis indicates that the major response elements for JNK in the AChE promoter are the AP1-like element (TGAGTCT) site, located within the -1565/-1569 region of the AChE promoter, and the ATF2 element (CCACGTCA), within the -2185/-2177 region. The AP1-like element binds to the transcription factors, c-jun and ATF2, while the ATF2 element binds mainly ATF2. Taken together, our results strongly suggest that H2O2 induces AChE expression via the JNK/AP1/ ATF2 signaling pathway.
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PMID:The JNK/AP1/ATF2 pathway is involved in H2O2-induced acetylcholinesterase expression during apoptosis. 1838 43