Scammell Jonathan G
Departments of Comparative Medicine and Pharmacology, Frederick P. Whiddon College of Medicine, University of South Alabama, Mobile, Alabama, USA.
J Cell Biochem. 2024 Dec;125(12):e30375. doi: 10.1002/jcb.30375. Epub 2023 Jan 30.
Many New World primates are glucocorticoid-resistant secondary to expression of low affinity glucocorticoid receptors. We identified the role of FKBP51 in hormone responsiveness by showing that multiple cell lines derived from New World primates share the same activities: (1) soluble cell extracts conferred low binding affinity to high affinity glucocorticoid receptors; (2) FK506 increased receptor binding in soluble cell extracts; and (3) cellular FKBP51 was elevated and FKBP52 was lower. Details of these cell lines and their availability are described. Subsequently, we showed that New World primate and human FKBP51 decreased glucocorticoid activity in heterologous COS-7 cell cultures. Future studies using the FKBP51 antagonist SAFit2 in New World primates are proposed.
许多新大陆灵长类动物由于低亲和力糖皮质激素受体的表达而对糖皮质激素产生抗性。我们通过表明源自新大陆灵长类动物的多种细胞系具有相同的活性来确定FKBP51在激素反应性中的作用：（1）可溶性细胞提取物赋予高亲和力糖皮质激素受体低结合亲和力；（2）FK506增加可溶性细胞提取物中的受体结合；以及（3）细胞FKBP51升高而FKBP52降低。描述了这些细胞系的详细信息及其可用性。随后，我们表明新大陆灵长类动物和人类的FKBP51在异源COS-7细胞培养物中降低了糖皮质激素活性。建议在新大陆灵长类动物中使用FKBP51拮抗剂SAFit2进行未来研究。
