Faculty of Medicine, Institute of Biochemistry, University of Nis, Nis, Serbia.
Amino Acids. 2010 Jun;39(1):29-43. doi: 10.1007/s00726-010-0489-3. Epub 2010 Feb 19.
Glucocorticoid hormones (GC) are essential in all aspects of human health and disease. Their anti-inflammatory and immunosuppressive properties are reasons for therapeutic application in several diseases. GC suppress immune activation and uncontrolled overproduction and release of cytokines. GC inhibit the release of pro-inflammatory cytokines and stimulate the production of anti-inflammatory cytokines. Investigation of GC's mechanism of action, suggested that polyamines (PA) may act as mediators or messengers of their effects. Beside glucocorticoids, spermine (Spm) is one of endogenous inhibitors of cytokine production. There are many similarities in the metabolic actions of GC and PA. The major mechanism of GC effects involves the regulation of gene expression. PA are essential for maintaining higher order organization of chromatin in vivo. Spermidine and Spm stabilize chromatin and nuclear enzymes, due to their ability to form complexes with negatively charged groups on DNA, RNA and proteins. Also, there is an increasing body of evidence that GC and PA change the chromatin structure especially through acetylation and deacetylation of histones. GC display potent immunomodulatory activities, including the ability to induce T and B lymphocyte apoptosis, mediated via production of reactive oxygen species (ROS) in the mitochondrial pathway. The by-products of PA catabolic pathways (hydrogen peroxide, amino aldehydes, acrolein) produce ROS, well-known cytotoxic agents involved in programmed cell death (PCD) or apoptosis. This review is an attempt in the better understanding of relation between GC and PA, naturally occurring compounds of all eukaryotic cells, anti-inflammatory and apoptotic agents in physiological and pathological conditions connected to oxidative stress or PCD.
糖皮质激素（GC）在人类健康和疾病的各个方面都至关重要。其抗炎和免疫抑制特性是在多种疾病中应用于治疗的原因。GC 抑制免疫激活和细胞因子的不受控制的过度产生和释放。GC 抑制促炎细胞因子的释放并刺激抗炎细胞因子的产生。GC 作用机制的研究表明，多胺（PA）可能作为其作用的介质或信使。除了糖皮质激素，亚精胺（Spm）是细胞因子产生的内源性抑制剂之一。GC 和 PA 的代谢作用有许多相似之处。GC 作用的主要机制涉及基因表达的调节。PA 对于维持体内染色质的高级结构是必需的。由于其能够与 DNA、RNA 和蛋白质上的带负电荷的基团形成复合物，因此 spermidine 和 Spm 稳定染色质和核酶。此外，越来越多的证据表明 GC 和 PA 通过组蛋白的乙酰化和去乙酰化来改变染色质结构。GC 表现出强大的免疫调节活性，包括诱导 T 和 B 淋巴细胞凋亡的能力，这是通过在线粒体途径中产生活性氧（ROS）介导的。PA 分解代谢途径的副产物（过氧化氢、氨基酸醛、丙烯醛）产生 ROS，这是参与程序性细胞死亡（PCD）或凋亡的已知细胞毒性剂。这篇综述试图更好地理解 GC 和 PA 之间的关系，PA 是所有真核细胞中自然存在的化合物，在与氧化应激或 PCD 相关的生理和病理条件下具有抗炎和凋亡作用。
