engleski

Metallothionein expression and tissue metal kinetics after partial hepatectomy in mice

Introduction: Metallothioneins (MTs) are the stress response proteins that have the profound growth-regulatory effects in rapidly dividing tissues, as well as the modulatory effects on neuro-immune response, induced by various stressors, including inflammatory agents, heavy metal cations, free radicals and organic compounds. In adults, they might be markedly upregulated by partial hepatectomy (pHx), which induces the highly orchestrated changes in growth factors and cytokine-related network, resulting in liver regeneration. Since MT regulate the cellular activities through binding and release of metals, in this study we attempted to analyze the interrelationship between the expression of MT- proteins and mRNA and metal tissue kinetics of zinc, iron, magnesium and calcium kinetics in the regeneration liver, thymus and spleen after pHx. Material & Method: Analysis were done on 1st, 2nd, 6th, 12th, 24th and 48th hour after 1/3 pHx in C57Bl mice, using immunohistological staining, RT-PCR and inductivity coupled plasma spectrometry for determination of MTs and tissue metals kinetics, respectively. Results: Hepatectomy was followed by fast upregulation of MT expression in the remnant liver, but also in the spleen and the thymus. In the liver it started in sinusoids (1h after pHx) and became impressive in hepatocytes (between the 6th and 72nd hour), where cytoplasmic and nuclear staining was seen (between the 6th and 72nd hour). Additionally, in hepatic and splenic tissue increased the MT-I mRNA, while on several splenic and thymic mononuclear lymphatic cells the increased expression of MT proteins was found in the cytoplasm and nuclei. Simultaneously, two hours after pHx the regenerating liver accumulated Zn2+, Ca2+, Mg2+ and Fe2+ ions while simultaneously decreased the concentration of all these metals in the spleen, and of Zn2+ in the thymus. On the 24th hour a new high accumulation of Zn2+ and Ca2+ was seen in the regenerating liver, and of Zn2+, Ca2+ and Fe2+ in the spleen. Moreover, in regenerating liver the areas expressing MTs inversely correlated with those containing apoptotic cells. Conclusions: The data emphasize that MTs and tissue metals may regulate the multiple pathways activated by pHx in mice, participating in reestablishment of morphostasis. (Supported by grants from Croatian Ministry of Science, project No 0062018).

metallothionein I+II; partial hepatectomy; metal tissue kinetics

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