Flower R J, Rothwell N J
Department of Biochemical Pharmacology, Medical College, St Bartholomew's Hospital, London, UK.
Trends Pharmacol Sci. 1994 Mar;15(3):71-6. doi: 10.1016/0165-6147(94)90281-x.
Lipocortin-1, a 37 kDa member of the annexin superfamily of proteins, originally evoked interest as one of the 'second messengers' of the anti-inflammatory actions of the glucocorticoids. Subsequent research has shown that the protein plays a major regulatory role in systems as diverse as cell-growth regulation and differentiation, neutrophil migration, CNS responses to cytokines, neuroendocrine secretion and neurodegeneration. The role of lipocortin-1 in mediating glucocorticoid-induced effects in these systems has been demonstrated using immunoneutralization strategies and by mimicking steroid actions with highly purified or recombinant lipocortin-1 or its biologically active peptide fragments. Originally the mode of action of lipocortin-1 seemed to be largely through inhibition of prostaglandin formation, but it is now clear that it can modify other aspects of cell function, perhaps pointing to a more fundamental mechanism than was originally envisaged. In this article Rod Flower and Nancy Rothwell review the nature, possible mechanisms and clinical relevance of these diverse actions of lipocortin-1.
脂皮质蛋白-1是膜联蛋白超家族中一种分子量为37 kDa的蛋白质，最初作为糖皮质激素抗炎作用的“第二信使”之一引起了人们的关注。随后的研究表明，该蛋白在细胞生长调节与分化、中性粒细胞迁移、中枢神经系统对细胞因子的反应、神经内分泌分泌和神经退行性变等多种系统中发挥着主要调节作用。利用免疫中和策略，以及通过用高度纯化或重组的脂皮质蛋白-1或其生物活性肽片段模拟类固醇作用，已证实脂皮质蛋白-1在介导这些系统中糖皮质激素诱导的效应方面所起的作用。最初，脂皮质蛋白-1的作用方式似乎主要是通过抑制前列腺素的形成，但现在很清楚，它可以改变细胞功能的其他方面，这可能表明其机制比最初设想的更为基本。在本文中，罗德·弗劳尔和南希·罗斯韦尔综述了脂皮质蛋白-1这些多样作用的性质、可能机制及临床相关性。
