CALCIUM ION TRANSPORT ATPASE AND ALTERED CALCIUM ION HOMEOSTASIS

钙离子转运ATP酶和改变的钙离子稳态

• 批准号: 6349161
• 负责人: Arif Hussain
• 金额: $ 22.3万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6349161
• 关键词: calcium flux; calcium metabolism; calcium transporting ATPase; cell line; enzyme activity; enzyme inhibitors; enzyme mechanism; enzyme structure; gene expression; homeostasis; hydroquinones; protein structure function; sarcoplasmic reticulum; thapsigargin

Intracellular Ca2+ plays a fundamental role in many cellular processes including proliferation, differentiation, and muscle contraction/relation. he sarcoplasmic/endoplasmic reticulum Ca2+ transport ATPase (SERCAs) are key enzymes involved in the regulation of cytoplasmic Ca2+ and intracellular Ca2_ stores. Alterations in SERCA expression and/or function can occur under certain physiological or pathophysiological conditions including hypertension and heart failure. Specific inhibitors of the SERCA pump are increasingly being used to study: (1) intracellular Ca2+ homeostasis, (2) regulation of SERCA gene expression, and (3) structure-function relationships within SERCA. We have developed a novel model system based on these SERCA pump inhibitors, which forms the basis for the current application. In particular, we have developed, under various selection strategies, mammalian cell lines that are highly resistant to the inhibitor effects of the specific SERCA pump blockers thapsigargin (TG) and 2,5- di(tert-butyl)-1, 4 hydroquinone (DBHQ). This results in certain biochemical and functional adaptations with respect to cellular Ca2+ homeostasis and SERCA pumps in the resistant cell lines. In this application, we propose a series of detailed molecular biological studies o the SERCA pumps present in the resistant cell lines in order to dissect the potential range of adaptations that can occur within them with respect to expression and function under such specific selective pressure. These studies will yield novel information regarding mechanisms controlling altered (and potentially pathologic) Ca2+ homeostasis, which are relevant and important to understanding disease states associated with abnormalities in Ca2+ homeostasis.

细胞内Ca2+在许多细胞过程中起着重要作用