Strategies for Analyzing the Processing of Proopiomelanocortin

阿黑皮质素原加工分析策略

• 批准号: 9412115
• 负责人: Robert Dores
• 金额: $ 16.63万
• 依托单位: University of Denver
• 依托单位国家: 美国
• 项目类别: Continuing grant
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-08-15 至 1997-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9412115&HistoricalAwards=false
• 关键词: Strategies; Analyzing; Processing; Proopiomelanocortin

IBN-9412115 Robert Dores The pituitary gland is the site for synthesis of several polypeptide hormones which are used as chemical messenger to influence a variety of functions such as growth, reproduction, and chronic stress regulation. One characteristic of polypeptide hormones is that the molecule that is first synthesized inside the cell (called a prohormone) is biologically inactive and must undergo a variety of processing steps by enzymes to convert the non-functional prohormone into a biologically active hormone. One of these important prohormones is proopiomelanocortin (POMC) found in the intermediate pituitary. POMC is the common prohormone for adrenocorticotropin, melanocyte-stimulating hormone, and the endogenous opioid, beta-endorphin. After POMC is synthesized, it undergoes a number of processing steps to make these active hormones. The sites inside the cell where the enzymatic reactions take place and the regulation and nature of the enzymes involved are poorly understood. This is a proposal to study in melanotropic cells of the anuran amphibian, Bufo marinus, the subcellular coordination of two important enzymes (prohormone convertase 1 and 2) that are involved in the processing and the location inside the cell where this processing occurs. Since the proper synthesis of pituitary hormones is essential to the survival of all vertebrates, these studies are critical for providing new insights into the cell biology of pituitary cells.

垂体是合成几种多肽激素的场所，这些激素被用作影响多种功能的化学信使，如生长、繁殖和慢性应激调节。多肽激素的一个特点是，最初在细胞内合成的分子（称为原激素）是无生物活性的，必须经过各种酶的处理步骤才能将无功能的原激素转化为具有生物活性的激素。这些重要的原激素之一是在垂体中间发现的促黑色素皮质素（POMC）。POMC是促肾上腺皮质激素、促黑素细胞激素和内源性阿片样物质-内啡肽的常见原激素。在POMC被合成后，它经历了一系列的加工步骤来制造这些活性激素。细胞内酶促反应发生的位置以及所涉及的酶的调节和性质尚不清楚。本研究拟在无性两栖动物Bufo marinus的嗜黑细胞中研究两种重要的酶（激素原转化酶1和2）的亚细胞协调，以及这一加工在细胞内发生的位置。由于垂体激素的适当合成对所有脊椎动物的生存至关重要，因此这些研究对于为垂体细胞的细胞生物学提供新的见解至关重要。