Metabolic correlations of glucocorticoids and polyamines in inflammation and apoptosis |
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Authors: | G Bjelaković I Stojanović T Jevtović Stoimenov D Pavlović G Kocić S Rossi C Tabolacci J Nikolić D Sokolović Lj Bjelakovic |
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Institution: | (1) Faculty of Medicine, Institute of Biochemistry, University of Niš, Nis, Serbia;(2) Department of Biology, University “Tor Vergata”, Via della Ricerca Scientifica, 00133 Rome, Italy |
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Abstract: | 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. |
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