Aruna Kilaru, Pamela Tamura, Puja Garg, Giorgis Isaac, David Baxter, R Scott Duncan, Ruth Welti, Peter Koulen, Kent D Chapman, Barney J Venables
{"title":"大鼠脑缺血/再灌注模型中n -酰基乙醇胺通路相关代谢物的变化","authors":"Aruna Kilaru, Pamela Tamura, Puja Garg, Giorgis Isaac, David Baxter, R Scott Duncan, Ruth Welti, Peter Koulen, Kent D Chapman, Barney J Venables","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>In mammals, the endocannabinoid signaling pathway provides protective cellular responses to ischemia. Previous work demonstrated increases in long-chain <i>N</i>-acylethanolamines (NAE) in ischemia and suggested a protective role for NAE. Here, a targeted lipidomics approach was used to study comprehensive changes in the molecular composition and quantity of NAE metabolites in a rat model of controlled brain ischemia. Changes of NAE, its precursors, <i>N</i>-acylphosphatidylethanolamines (NAPE), major and minor phospholipids, and free fatty acids (FFA) were quantified in response to ischemia. The effect of intraperitoneal injection of <i>N</i>-palmitoylethanolamine (NAE 16:0) prior to ischemia on NAE metabolite and phospholipid profiles was measured. While ischemia, in general, resulted in elevated levels of <i>N</i>-acyl 16:0 and18:0 NAE, NAPE, and FFA species, pretreatment with NAE 16:0 reduced infarct volume, neurological behavioral deficits in rats, and FFA content in ischemic tissues. Pretreatment with NAE 16:0 did not affect the profiles of other NAE metabolites. These studies demonstrate the utility of a targeted lipidomics approach to measure complex and concomitant metabolic changes in response to ischemia. They suggest that the neuroprotective effects of exogenous NAE 16:0 and the reduction in inflammatory damage may be mediated by factors other than gross changes in brain NAE levels, such as modulation of transcriptional responses.</p>","PeriodicalId":89585,"journal":{"name":"Journal of glycomics & lipidomics","volume":"1 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457465/pdf/nihms690267.pdf","citationCount":"0","resultStr":"{\"title\":\"Changes in N-acylethanolamine Pathway Related Metabolites in a Rat Model of Cerebral Ischemia/Reperfusion.\",\"authors\":\"Aruna Kilaru, Pamela Tamura, Puja Garg, Giorgis Isaac, David Baxter, R Scott Duncan, Ruth Welti, Peter Koulen, Kent D Chapman, Barney J Venables\",\"doi\":\"\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>In mammals, the endocannabinoid signaling pathway provides protective cellular responses to ischemia. Previous work demonstrated increases in long-chain <i>N</i>-acylethanolamines (NAE) in ischemia and suggested a protective role for NAE. Here, a targeted lipidomics approach was used to study comprehensive changes in the molecular composition and quantity of NAE metabolites in a rat model of controlled brain ischemia. Changes of NAE, its precursors, <i>N</i>-acylphosphatidylethanolamines (NAPE), major and minor phospholipids, and free fatty acids (FFA) were quantified in response to ischemia. The effect of intraperitoneal injection of <i>N</i>-palmitoylethanolamine (NAE 16:0) prior to ischemia on NAE metabolite and phospholipid profiles was measured. While ischemia, in general, resulted in elevated levels of <i>N</i>-acyl 16:0 and18:0 NAE, NAPE, and FFA species, pretreatment with NAE 16:0 reduced infarct volume, neurological behavioral deficits in rats, and FFA content in ischemic tissues. Pretreatment with NAE 16:0 did not affect the profiles of other NAE metabolites. These studies demonstrate the utility of a targeted lipidomics approach to measure complex and concomitant metabolic changes in response to ischemia. They suggest that the neuroprotective effects of exogenous NAE 16:0 and the reduction in inflammatory damage may be mediated by factors other than gross changes in brain NAE levels, such as modulation of transcriptional responses.</p>\",\"PeriodicalId\":89585,\"journal\":{\"name\":\"Journal of glycomics & lipidomics\",\"volume\":\"1 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2011-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457465/pdf/nihms690267.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of glycomics & lipidomics\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of glycomics & lipidomics","FirstCategoryId":"1085","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Changes in N-acylethanolamine Pathway Related Metabolites in a Rat Model of Cerebral Ischemia/Reperfusion.
In mammals, the endocannabinoid signaling pathway provides protective cellular responses to ischemia. Previous work demonstrated increases in long-chain N-acylethanolamines (NAE) in ischemia and suggested a protective role for NAE. Here, a targeted lipidomics approach was used to study comprehensive changes in the molecular composition and quantity of NAE metabolites in a rat model of controlled brain ischemia. Changes of NAE, its precursors, N-acylphosphatidylethanolamines (NAPE), major and minor phospholipids, and free fatty acids (FFA) were quantified in response to ischemia. The effect of intraperitoneal injection of N-palmitoylethanolamine (NAE 16:0) prior to ischemia on NAE metabolite and phospholipid profiles was measured. While ischemia, in general, resulted in elevated levels of N-acyl 16:0 and18:0 NAE, NAPE, and FFA species, pretreatment with NAE 16:0 reduced infarct volume, neurological behavioral deficits in rats, and FFA content in ischemic tissues. Pretreatment with NAE 16:0 did not affect the profiles of other NAE metabolites. These studies demonstrate the utility of a targeted lipidomics approach to measure complex and concomitant metabolic changes in response to ischemia. They suggest that the neuroprotective effects of exogenous NAE 16:0 and the reduction in inflammatory damage may be mediated by factors other than gross changes in brain NAE levels, such as modulation of transcriptional responses.