کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2581616 | 1561653 | 2008 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Organophosphate-sensitive lipases modulate brain lysophospholipids, ether lipids and endocannabinoids
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
Organophosphorus - ارگانوفسفورAcetylcholinesterase - استیل کولین استرازFatty acid amide hydrolase - اسید آمینه هیدرولاز اسید چربInsecticide - حشرهکشSerine hydrolase - سریال هیدرولازChemical warfare agent - عامل جنگ شیمیاییmonoacylglycerol lipase - لیپاز monoacylglycerol لیپازhormone-sensitive lipase - لیپاز حساس به هورمونBrain - مغزneuropathy target esterase - نوراستیک هدف استراز
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Lipases play key roles in nearly all cells and organisms. Potent and selective inhibitors help to elucidate their physiological functions and associated metabolic pathways. Organophosphorus (OP) compounds are best known for their anticholinesterase properties but selectivity for lipases and other targets can also be achieved through structural optimization. This review considers several lipid systems in brain modulated by highly OP-sensitive lipases. Neuropathy target esterase (NTE) hydrolyzes lysophosphatidylcholine (lysoPC) as a preferred substrate. Gene deletion of NTE in mice is embryo lethal and the heterozygotes are hyperactive. NTE is very sensitive in vitro and in vivo to direct-acting OP delayed neurotoxicants and the related NTE-related esterase (NTE-R) is also inhibited in vivo. KIAA1363 hydrolyzes acetyl monoalkylglycerol ether (AcMAGE) of the platelet-activating factor (PAF) de novo biosynthetic pathway and is a marker of cancer cell invasiveness. It is also a detoxifying enzyme that hydrolyzes chlorpyrifos oxon (CPO) and some other potent insecticide metabolites. Monoacylglycerol lipase and fatty acid amide hydrolase regulate endocannabinoid levels with roles in motility, pain and memory. Inhibition of these enzymes in mice by OPs, such as isopropyl dodecylfluorophosphonate (IDFP), leads to dramatic elevation of brain endocannabinoids and distinct cannabinoid-dependent behavior. Hormone-sensitive lipase that hydrolyzes cholesteryl esters and diacylglycerols is a newly recognized in vivo CPO- and IDFP-target in brain. The OP chemotype can therefore be used in proteomic and metabolomic studies to further elucidate the biological function and toxicological significance of lipases in lipid metabolism. Only the first steps have been taken to achieve appropriate selective action for OP therapeutic agents.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemico-Biological Interactions - Volume 175, Issues 1â3, 25 September 2008, Pages 355-364
Journal: Chemico-Biological Interactions - Volume 175, Issues 1â3, 25 September 2008, Pages 355-364
نویسندگان
John E. Casida, Daniel K. Nomura, Sarah C. Vose, Kazutoshi Fujioka,