Electronic Resource
Comparison of Human and Guinea Pig Acetylcholinesterase Sequences and Rates of Oxime-Assisted Reactivation
| العنوان: | Comparison of Human and Guinea Pig Acetylcholinesterase Sequences and Rates of Oxime-Assisted Reactivation |
|---|---|
| المؤلفون: | ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD, Cadieux, C. L., Broomfield, Clarence A., Kirkpatrick, Melanie G., Kazanski, Meghan E., Lenz, David E., Cerasoli, Douglas M. |
| المصدر: | DTIC |
| بيانات النشر: | 2010 |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Poisoning via organophosphorus (OP) nerve agents occurs when the OP binds and inhibits the enzyme acetylcholinesterase (AChE). This enzyme is responsible for the metabolism of the neurotransmitter acetylcholine (ACh) which transmits signals between nerves and several key somatic regions. When AChE is inhibited, the signal initiated by ACh is not properly terminated. Excessive levels of ACh result in a cholinergic crisis, and in severe cases can lead to death. Current treatments for OP poisoning involve the administration of atropine, which blocks ACh receptors, and oximes, which reactivate AChE after inhibition. Efforts to improve the safety, efficacy, and broad spectrum utility of these treatments are ongoing and usually require the use of appropriate animal model systems. For OP poisoning, the guinea pig (Cavia porcellus) is a commonly used animal model because guinea pigs more closely mirror primate susceptibility to OP poisoning than do other animals such as rats and mice. This is most likely because among rodents and other small mammals, guinea pigs have a very low relative concentration of serum carboxylesterase, an enzyme known to bind OPs in vitro and to act as an endogenous bioscavenger in vivo. Although guinea pigs historically have been used to test OP poisoning therapies, it has been found recently that guinea pig AChE is substantially more resistant to oxime-mediated reactivation than human AChE. To examine the molecular basis for this difference, we reverse transcribed mRNA encoding guinea pig AChE, amplified the resulting cDNA, and sequenced this product. The nucleotide and deduced amino acid sequences of guinea pig AChE were then compared to the human version. Several amino acid differences were noted, and the predicted locations of these differences were mapped onto a structural model of human AChE. To examine directly how these differences affect oxime-mediate reactivation of AChE were determined. Published in Chemico-Biological Interactions ,v187, p229-233, 2010., The original document contains color images. Sponsored in part by Defense Threat Reduction. |
| مصطلحات الفهرس: | Biochemistry, Organic Chemistry, Chemical, Biological and Radiological Warfare, NERVE AGENTS, ORGANOPHOSPHATES, ACETYLCHOLINESTERASE, METABOLISM, ENZYMES, PAIN, BLOOD SERUM, INHIBITION, DEATH, IN VIVO ANALYSIS, ESTERASES, RECEPTOR SITES(PHYSIOLOGY), AMINO ACIDS, CHEMICAL WARFARE AGENTS, ATROPINE, GUINEA PIGS, OXIMES, ACETYLCHOLINE, NUCLEOTIDES, CARBOXYL RADICALS, PRIMATES, POISONING, THERAPY, IN VITRO ANALYSIS, MAMMALS, NEUROTRANSMITTERS, ORGANOPHOSPHORUS POISONING, ORGANOPHOSPHORUS, REACTIVATION, Text |
| URL: | |
| الاتاحة: | Open access content. Open access content Approved for public release; distribution is unlimited. |
| ملاحظة: | text/html English |
| Other Numbers: | DTICE ADA539573 832111575 |
| المصدر المساهم: | From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.ocn832111575 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |