EPR Oximetry to Study Diabetic Endothelial Dysfunction

EPR 血氧测定法研究糖尿病内皮功能障碍

• 批准号: 7155969
• 负责人: Tennille D Presley
• 金额: $ 3.3万
• 依托单位: OHIO STATE UNIVERSITY
• 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 2007-08-26
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7155969
• 关键词: cell line; cellular respiration; diabetes mellitus; electrochemistry; electron spin resonance spectroscopy; gene induction /repression; glucose; heat shock proteins; hyperglycemia; nitric oxide synthase; oxygen transport; phthalocyanin; predoctoral investigator; superoxides; transfection; vascular endothelium

DESCRIPTION (provided by applicant): The overall aim of this proposal is to determine whether the endothelial cells of diabetic patients consume less oxygen than in normal cases. To achieve this goal, a novel technique, namely "electron paramagnetic resonance (EPR) oximetry" will be used. EPR oximetry has been developed and successfully utilized in many biological conditions to understand the regulation of respiration in isolated cells. A higher concentration of glucose, known as hyperglycemia, impairs the association of a scaffold protein, heat shock protein 90 (Hsp90) with endothelial nitric oxide syntheses (eNOS). This results in a reduced generation of nitric oxide (NO) and an increased generation of superoxide (O2-). On the other hand, both NO and O2- are known to regulate respiration in the endothelium and hence, excess glucose is expected to alter the respiration of endothelial cells. The aims of this proposal are to measure the respiration at hyperglycemic conditions, as well as hyperglycemic conditions when Hsp90 is over expressed in endothelial cells. The expected outcome of this study is to be able to determine whether hyperglycemic dysfunction of the diabetic endothelium is contributed by an alteration in the respiration.

描述（由申请人提供）：本提案的总体目标是确定糖尿病患者的内皮细胞是否比正常情况下消耗更少的氧气。 为了实现这一目标，将使用一种新的技术，即“电子顺磁共振（EPR）血氧测定法”。 EPR血氧测定法已被开发并成功地用于许多生物条件下，以了解在分离的细胞呼吸的调节。 较高浓度的葡萄糖，称为高血糖症，损害支架蛋白热休克蛋白90（Hsp 90）与内皮一氧化氮合成酶（eNOS）的关联。 这导致一氧化氮（NO）的生成减少和超氧化物（O2-）的生成增加。另一方面，已知NO和O2-都调节内皮细胞的呼吸，因此，预期过量的葡萄糖会改变内皮细胞的呼吸。 该提议的目的是测量高血糖条件下的呼吸，以及当Hsp 90在内皮细胞中过表达时的高血糖条件。 本研究的预期结果是能够确定糖尿病内皮的高血糖功能障碍是否由呼吸的改变引起。