Statins induce the glucocorticoid-induced leucine zipper protein GILZ: mechanisms and functional implications

他汀类药物诱导糖皮质激素诱导的亮氨酸拉链蛋白 GILZ：机制和功能意义

• 批准号: 353717108
• 负责人: Professorin Dr. Alexandra K. Kiemer
• 金额: --
• 依托单位: Institut für Pharmazeutische Biologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/353717108?language=en
• 关键词: Statins; induce; glucocorticoid; induced; leucine

Statins represent the most widely prescribed class of drugs worldwide. They convey a distinct protection from cardiovascular pathologies, which are facilitated via both lipid-lowering and anti-inflammatory actions. Myopathies represent the most common side effects, which range from mild muscle pain to life-threatening rhabdomyolyses. The glucocortioid induced leucine zipper protein GILZ has been reported to exhibit distinct anti-infammatory actions. Aim of the project is to test the hypothesis that the induction of GILZ substantially contributes to the desired actions of statins, but that GILZ also plays a role in their undesired effects. The following questions will be answered in order to test the hypothesis:- In which cell types do statins induce GILZ?- What are the mechanisms for GILZ induction?- Does GILZ contribute to the anti-inflammatory actions of statins?- Does GILZ induction facilitate effects of statins on muscle?Answering these questions can substantially contribute to a better understanding of the mechanisms of action of this important class of drugs, but can also help to better understand adverse side effects.

他汀类药物是全世界处方最广泛的一类药物。它们对心血管病理有明显的保护作用，这是通过降脂和抗炎作用来促进的。肌病是最常见的副作用，从轻微的肌肉疼痛到危及生命的横纹肌溶解症。据报道，糖皮质激素诱导的亮氨酸拉链蛋白 GILZ 具有独特的抗炎作用。该项目的目的是检验以下假设：GILZ 的诱导很大程度上有助于他汀类药物的预期作用，但 GILZ 也在其不良作用中发挥作用。为了检验该假设，将回答以下问题：- 他汀类药物在哪些细胞类型中诱导 GILZ？- GILZ 诱导机制是什么？- GILZ 是否有助于他汀类药物的抗炎作用？- GILZ 诱导是否促进他汀类药物对肌肉的作用？回答这些问题可以大大有助于更好地理解这一类重要药物的作用机制，也可以帮助更好地理解 不良副作用。