Signaling for cardioprotection against oxidative stress

超出所提供的空间。心脏有内源性的保护机制来抵抗氧化应激引起的损伤。然而，导致心肌损伤预防和保护的细胞机制尚未明确。缺乏这方面的知识妨碍了旨在预防和/或治疗心脏病的新治疗策略的发展。我的长期目标是确定信号转导机制，导致成人心肌细胞的保护。本应用程序的目的是专门评估GATA-4在肝细胞生长因子和内皮素- 1诱导的细胞存活信号传导中的作用。该应用的中心假设是肝细胞生长因子和内皮素-1保护心肌细胞免受氧化应激诱导的细胞死亡，部分原因是通过激活GATA-4上调细胞存活基因。这一假设是基于大量的初步数据提出的，这些数据表明肝细胞生长因子和内皮素-1保护心肌细胞免受氧化应激并激活GATA-4。提出这项研究的基本原理是，一旦获得了保护心肌细胞的机制的知识，它将导致可用于预防和/或治疗心脏病的新策略，从而降低与该病症相关的发病率和死亡率。我有独特的准备来进行拟议的研究，因为我的实验室已经证明肝细胞生长因子和内皮素-1保护成人心肌细胞免受氧化应激，也磷酸化GATA-4，因此许多技术和试剂已经可用。中心假设将通过以下两个具体目标得到验证：1)确定GATA-4激活的机制；2)确定肝细胞生长因子和内皮素-1保护心肌细胞的共同机制。提出的工作是创新的，因为它将结合成人心肌细胞的细胞和动物模型。我希望GATA-4在心肌细胞保护的信号转导中发挥重要作用。这些结果将具有重要意义，因为它们有望为心脏病的预防和治疗干预提供新的药物。此外，预计这一结果将从根本上推动心肌细胞生物学领域的发展。网站性能 ======================================== 节结束 ===========================================

EXCEED THE SPACE PROVIDED. The heart has endogenous protective mechanisms against oxidative stress-induced damage. The cellular mechanisms that lead to the prevention and protection of myocardial damage, however, have not been defined. Lack of such knowledge interferes with the development of new therapeutic strategies that are designed to prevent and/or treat heart disease. My long-range goal is to identify the signal transduction mechanisms, leading to the protection of adult cardiac myocytes. The objective of this application is to evaluate specifically the role of GATA-4 in cell survival signaling induced by hepatocyte growth factor and endothelin-l. The central hypothesis of the application is that hepatocyte growth factor and endothelin-1 protect cardiac myocytes against oxidative stress-induced cell death, in part, by upregulating cell survival genes via the activation of GATA-4. The hypothesis has been formulated on the basis of strong preliminary data, which suggest that hepatocyte growth factor and endothelin-1 protect cardiac myocytes against oxidative stress and activate GATA-4. The rationale for the proposed research is that, once knowledge of the mechanisms that are responsible for the protection of cardiac myocytes has been obtained, it will lead to new strategies that can be used to prevent and/or treat heart disease, thereby reducing the morbidity and mortality that are associated with this condition. I am uniquely prepared to undertake the proposed research because my laboratory has demonstrated that hepatocyte growth factor and endothelin-1 protect adult cardiac myocytes against oxidative stress and also phosphorylate GATA-4, thus many of the techniques and reagents are already available. The central hypothesis will be tested and the objective of the application accomplished by pursuing two specific aims: 1) Determine the mechanism of GATA-4 activation, and 2) Determine the common mechanism by which hepatocyte growth factor and endothelin-1 protect cardiac myocytes. The proposed work is innovative, because it will combine cellular and animal models of adult cardiac myocytes. It is my expectation that GATA-4 plays an important role in signal transduction for cardiac myocyte protection. These results will be significant because they are expected to provide new agents for preventative and therapeutic interventions for heart disease. In addition, it is expected that the results will fundamentally advance the field of cardiac muscle cell biology. PERFORMANCE SITE ========================================Section End===========================================