REGULATION OF INDUCIBLE RAT SALIVARY CYSTATIN

胱抑素超家族的半胱氨酸蛋白酶抑制剂分为 根据分子结构分为三个科。族1 半胱氨酸类主要存在于细胞内，并以成分性存在 许多大鼠组织的成分。家族2主要存在于 细胞外液。激肽原是3族半胱氨酸氨基转移酶，主要存在于 电浆。家族1和3已经被很好地描述了 在大鼠模型系统中，但关于家族2的信息非常有限 大鼠的半胱氨酸菌素。一个家族2的半胱氨酸氨基转移酶最近被提纯， 我们对异丙肾上腺素唾液和颌下腺的测序 治疗过的老鼠。与家族1不同，后者是构成成分的 大鼠组织成分，家族2在正常大鼠中未检测到 纸巾。尽管家族3半胱氨酸氨基转移酶(激肽原)也起急性期的作用 大鼠血浆中的反应物，它们也存在于正常大鼠的血浆中。 这些观察表明，三者的生物合成和分泌 半胱氨酸类药物可能不同，每种都可能具有重要的生理作用 去打球。据推测，这些分子可能作为一种 内源性半胱氨酸浓度升高的防护措施 炎症期间的蛋白水解酶。自家系2大鼠在大鼠体内的胱抑素 颌下腺不是构成成分，而是 在异丙肾上腺素治疗后诱导，这提供了一个新的模型系统 研究炎症状态下该分子的生物合成和分泌 条件。这项初步研究的目的是研究 不同分泌物和试剂对2家族半胱氨酸氨基转移酶的诱导 已知会对唾液腺造成伤害。建议的目的是 研究目的是研究产生伤害的试剂对人体健康的影响 诱导家族2半胱氨酸氨基转移酶的转录和翻译调控 取自大鼠的颌下腺。免疫化学技术将被用于 大鼠颌下腺和唾液中胱抑素变化的研究 在体内和体外对颌下腺进行刺激。Cdna 将分离与家族2半胱氨酸氨基转移酶对应的克隆 研究转录调控。为了准确地理解 半胱氨酸氨基转移酶的重要性，重要的是了解它们的结构- 功能关系，并理解控制它们的机制 合成和分泌。根据在该试点中获得的信息 研究，我们希望将研究扩展到其他唾液腺模型 腺泡和导管细胞的损伤及其调控机制 更详细地说。这项工作的长期目标是使用 在大鼠模型中获得的信息作为研究阿糖胞苷的作用的基础 在正常和病理生理条件下的半胱氨酸类。

Cysteine proteinase inhibitors of the cystatin superfamily are grouped into three families on the basis of their molecular structure. Family 1 cystatins are found mainly intracellularly and are present as constituative components of many rat tissues. Family 2 cystatins are mainly present in extracellular fluids. Kininogens are family 3 cystatins, present mainly in the plasma. Family 1 and 3 cystatins have been fairly well characterized in rat model system but very limited information is available on family 2 cystatins of rat. A family 2 cystatin has been very recently purified and sequenced by us from the saliva and submandibular glands of isoproterenol treated rats. As opposed to family 1 cystatins, which are constituative component of rat tissues, family 2 cystatin is not detected in normal rat tissues. Although family 3 cystatins (kininogens) also act as acute-phase reactants in rat plasma, they are also present in the normal rat plasma. These observations suggest that biosynthesis and secretion of the three cystatins may be different and each may have important physiological role to play. It is speculated that these molecules may be involved as a protective measure against increased concentration of endogenous cysteine proteinases during inflammation. Since family 2 rat cystatin in rat submandibular gland is not present as a constituative component, but is induced following isoproterenol treatment, this offers a novel model system to study the biosynthesis and secretion of this molecule under inflammatory conditions. This pilot study is designed to study the feasibility of induction of family 2 cystatins by different secretogogues and agents, known to produce injury to the salivary glands. The aim of the proposed research is to study the effects of the injury producing reagents on the transcriptional and translational regulation of inducible family 2 cystatin from rat submandibular glands. Immunochemical techniques will be used to study the changes in the salivary and submandibular cystatin in rats following in vivo and in vitro stimulation of submandibular glands. cDNA clones corresponding to family 2 cystatin will be isolated and used to study the transcriptional control. In order to understand precisely the importance of cystatins, it is important to understand their structure- function relationship and to understand the mechanism which control their synthesis and secretion. Based on the information achieved in this pilot study, we would like to extend the study to other models of salivary gland injury of acinar and ductal cells and to understand these control mechanism in greater details. The long term goal of this work is to use the information gained in the rat model as a basis for the study of role of cystatins in normal and pathophysiological conditions.