Mezosi E, Szabo J, Nagy E V, Borbely A, Varga E, Paragh G, Varga Z
Divisions of Endocrinology and Metabolism, First Department of Medicine, University of Debrecen, Hungary.
J Endocrinol. 2005 Apr;185(1):121-9. doi: 10.1677/joe.1.05968.
Over the past few years increasing evidence has suggested the nongenomic effects of thyroid hormone, such as the activation of the signal transduction pathways and the activation of nuclear factor-kappaB by the induction of oxidative stress. The present study was undertaken to investigate the effect of thyroid hormone on human polymorphonuclear leukocytes (PMNLs) which are known as important sources of reactive oxygen species in the circulation. The production of superoxide anion (O2-) and the activity of myeloperoxidase were determined in the presence and absence of several inhibitors of the signalling pathway. L-thyroxine (T4) l-3,5,3'-tri-iodothyronine (T3) and L-3,5-di-iodothyronine (T2) stimulated O2- production in PMNLs in a dose-dependent manner within a few minutes of addition to cells. Thyroid hormone-stimulated O2- production was partially inhibited by pertussis toxin, an inhibitor of GTP-binding G protein, and was completely abolished by the protein kinase C inhibitors calphostin C and Ro-32-0432, and by a calcium chelator (BAPTA; bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid). Thyroid hormone stimulated myeloperoxidase activity and induced 125I- incorporation into PMNLs. Furthermore, thyroid hormone pre-incubation enhanced O2- production for n-formyl-methionyl-leucyl- phenylalanine (FMLP) stimulation. In conclusion, novel nongenomic actions of thyroid hormone, the induction of superoxide anion production and the stimulation of myeloperoxidase activity in PMNLs were demonstrated. The induction of O2- production requires calcium and is mediated by a pertussis toxin-sensitive G protein via stimulation of protein kinase C(s). These results suggest the existence of a membrane-bound binding site for thyroid hormone in PMNLs and a physiological role for thyroid hormone in the cellular defence mechanisms by stimulating free-radical production.
在过去几年中，越来越多的证据表明甲状腺激素具有非基因组效应，比如激活信号转导通路以及通过诱导氧化应激来激活核因子-κB。本研究旨在探究甲状腺激素对人多形核白细胞（PMNLs）的影响，已知PMNLs是循环中活性氧的重要来源。在存在和不存在几种信号通路抑制剂的情况下，测定超氧阴离子（O2-）的产生和髓过氧化物酶的活性。L-甲状腺素（T4）、L-3,5,3'-三碘甲状腺原氨酸（T3）和L-3,5-二碘甲状腺原氨酸（T2）在加入细胞后的几分钟内以剂量依赖的方式刺激PMNLs中O2-的产生。甲状腺激素刺激的O2-产生被百日咳毒素（一种GTP结合G蛋白的抑制剂）部分抑制，并被蛋白激酶C抑制剂钙泊三醇C和Ro-32-0432以及钙螯合剂（BAPTA；双（邻氨基苯氧基）乙烷-N,N,N',N'-四乙酸）完全消除。甲状腺激素刺激髓过氧化物酶活性并诱导125I掺入PMNLs。此外，甲状腺激素预孵育增强了对N-甲酰甲硫氨酰亮氨酰苯丙氨酸（FMLP）刺激的O2-产生。总之，证明了甲状腺激素的新型非基因组作用，即诱导超氧阴离子产生和刺激PMNLs中的髓过氧化物酶活性。O2-产生的诱导需要钙，并通过刺激蛋白激酶C由对百日咳毒素敏感的G蛋白介导。这些结果表明PMNLs中存在甲状腺激素的膜结合位点，以及甲状腺激素通过刺激自由基产生在细胞防御机制中的生理作用。
