Effect of Glutamine on HSP-70 Expression in ICU patients

谷氨酰胺对ICU患者HSP-70表达的影响

• 批准号: 7148394
• 负责人: PAUL E WISCHMEYER
• 金额: $ 15.4万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7148394
• 关键词: chemotherapy; clinical research; clinical trials; cytokine; endotoxins; enzyme linked immunosorbent assay; gene expression; glutamine; heat; heat shock proteins; hospital length of stay; human mortality; human subject; human therapy evaluation; inflammation; patient oriented research; phosphorylation; physiologic stressor; postoperative state; western blottings

DESCRIPTION (provided by applicant): It is well known that enhanced heat shock protein-70 (HSP-70) expression can protect cells and tissues from injury. Further, HSP-70 expression can improve survival in experimental models of critical illness. However, clinical application of these findings has not occurred, as known enhancers of HSP-70 are not safe for human administration. Thus, this very powerful tool, that could possibly significantly improve outcome in critically ill patients, has yet to be clinically applied. Our laboratory has shown that the amino acid glutamine (GLN) can enhance HSP-70 expression in tissues of stressed animals. This expression is correlated with improved survival following experimental models of critical illness. In a small initial trial of critically ill patients we demonstrated GLN could enhance serum HSP-70 levels after one-week of therapy. The effect of GLN on tissue HSP-70 expression and its potential to improve outcomes in patients is unknown. We propose three Specific Aims. The first examines GLN's effect on serum and cellular HSP-70 expression in healthy volunteers following a heat stress. This trial will assess if HSP-70 can be pre-induced to improve outcomes prior to a stressful event, such as surgery. The second Specific Aim will be to assess GLN's effect on serum and cellular HSP-70 expression in critical illness. The third Specific Aim will examine the effect of potentially enhanced HSP-70 expression on clinical outcomes. We believe this study will demonstrate that GLN is the first clinically viable enhancer of HSP-70 expression. The potential for such an agent to reduce morbidity/mortality in surgical and critical illness is significant.

描述（由申请人提供）： 众所周知，增强热休克蛋白 70 (HSP-70) 表达可以保护细胞和组织免受损伤。此外，HSP-70 表达可以提高危重疾病实验模型的存活率。然而，这些发现的临床应用尚未发生，因为已知的 HSP-70 增强剂对人体给药并不安全。因此，这种非常强大的工具可能会显着改善危重患者的治疗结果，但尚未应用于临床。我们的实验室已证明氨基酸谷氨酰胺 (GLN) 可以增强应激动物组织中 HSP-70 的表达。这种表达与危重病实验模型后生存率的提高相关。在一项针对危重患者的小型初步试验中，我们证明 GLN 可以在治疗一周后提高血清 HSP-70 水平。 GLN 对组织 HSP-70 表达的影响及其改善患者预后的潜力尚不清楚。我们提出三个具体目标。第一个研究检查了 GLN 对热应激后健康志愿者血清和细胞 HSP-70 表达的影响。该试验将评估是否可以在手术等应激事件之前预先诱导 HSP-70 以改善结果。第二个具体目标是评估 GLN 对危重疾病中血清和细胞 HSP-70 表达的影响。第三个具体目标将检查潜在增强的 HSP-70 表达对临床结果的影响。我们相信这项研究将证明 GLN 是第一个临床上可行的 HSP-70 表达增强剂。这种药物降低手术和危重疾病发病率/死亡率的潜力是巨大的。