The Effect of a Mixture of Pesticides on the Rat Cardiac Proteome

描述(申请人提供)：心血管疾病是当今美国的主要死亡原因，上个世纪一直如此。大约有7000万美国人患有某种形式的心血管疾病，其中许多人需要持续的药物治疗。密西西比州是美国所有州中经年龄调整后的心血管疾病死亡率最高的州。已知的心血管疾病风险因素可能是造成这种差异的主要原因，但其他因素也可能起到作用。越来越多的人认识到环境毒物在心血管疾病中的作用。密西西比州的经济以农业为基础，大部分人口居住在离农作物种植地很近的农村地区。这种接近导致人们接触到当前使用的杀虫剂以及遗留的杀虫剂，这些杀虫剂过去曾使用过，但今天在环境中持续存在。最近的研究表明，在宫内接触有机磷杀虫剂毒死蜱可以影响心肌细胞的腺苷环化酶信号通路。然而，关于农药在心血管疾病的发生、发展和药物治疗中的作用，人们知之甚少。这项拨款建议研究两种与环境有关的杀虫剂狄氏剂和毒死蜱对大鼠心脏蛋白质组的影响。狄氏剂是一种传统杀虫剂，在1950年的S和1960年的S中广泛使用(尽管目前在美国被禁用)。它仍然存在于密西西比河三角洲地区的土壤样本中。毒死蜱是目前使用的一种杀虫剂。这项资助的目标是确定其转录水平和/或翻译后修饰水平因接触这两种杀虫剂而发生变化的蛋白质。由此确定的蛋白质将有助于指导进一步的研究，以确定这些杀虫剂的毒性机制。我们的长期目标是更好地了解常用杀虫剂和其他环境化学品对心脏病及其治疗的影响程度。

DESCRIPTION (provided by applicant): Cardiovascular disease is the leading cause of death in the U.S. today and has been so for the last century. Approximately 70 million Americans suffer from some form of cardiovascular disease and many require ongoing pharmacological therapy. Mississippi has the highest annual age-adjusted death rate from cardiovascular disease of any state in the U.S. Known risk factors for cardiovascular disease probably account for much of this disparity but other factors may be playing a role. Increasingly, the role of environmental toxicants in cardiovascular disease is being recognized. Mississippi has an agricultural based economy and much of the population resides in rural settings close to where crops are grown. This proximity results in the contact of the population with current use pesticides as well as legacy pesticides, those pesticides used in the past but persistent in the environment today. Recent studies have shown exposure to chlorpyrifos, an organophosphate insecticide, in utero can affect the adenylyl cyclase signaling pathway in cardiac myocytes. However, little is known about the effect of pesticides on the development, progression, and pharmacological treatment of cardiovascular disease. This grant proposes to examine the effects of two environmentally relevant pesticides, dieldrin and chlorpyrifos, on the rat cardiac proteome. Dieldrin is a legacy pesticide used extensively in the 1950's and 1960's (though currently banned in the U.S.) which is still present in soil samples from the Mississippi Delta region. Chlorpyrifos is a pesticide in current use. The goal of this grant is to identify proteins whose levels of transcription and/or post-translational modifications are altered by exposure to these two pesticides. The proteins thus identified will serve to direct further studies aimed at identifying the mechanism of toxicity of these pesticides. Our long-term objective is to better understand the extent to which commonly used pesticides and other environmental chemicals influence heart disease and its treatment.