engleski

Fast metallothionein and tissue metal response to partial hepatectomy in regenerating liver, thymus and spleen

Introduction: Liver regeneration that follows after partial hepatectomy (pHx) is well-defined process, which involves the concerted action of extra and intracellular factors resulting in induction of cell replication and its inhibition at time when the entire liver mass is restored. Concomitantly, the breakdown of previously maintained tolerance and the exposure of self antigens lead to the activation of pre-immune and immune repertoire, which participate in surveillance against aberrant cells and re-establishment of previous morphostasis. Since, in these events, important biological function might have metallothioneins and tissue minerals which are affecting the structural integrity and enzyme activities, transduction signals, and replication factors during cell proliferation and apoptosis, as well as, the development and maintenance of immune functions, in this study we analyzed early metallothionein I+II (MT) expression and tissue kinetics of zinc, iron, magnesium and calcium in the 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 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). In the spleen a marked overexpression of MT was found in parafollicular areas 24h after pHx, while in the thymus MT staining moderately increased in the subcortical and medullar zones (after 24h). Simultaneously, in the regenerating liver, immediately after the operation, accumulated Zn++, Fe++, Mg++ and Ca++, while their concentrations significantly decreased in the thymus (Zn++) and in the spleen (Zn++, Fe++, Ca++ and Mg++). Conclusions: The data point to early activation of highly interconnected network of growth-factors and cytokine-regulated pathways by pHx, in which metallothioneins in the regenerating liver, thymus and spleen could participate in a DNA synthesis-related processes, and transduction signals through abstraction or donation of metals such as Zn++, Fe++, Mg++ and Ca++. ((Supported by grants from Croatian Ministry of Science, projects No 0062018 and 0062002).

partial hepatectomy; metallothionens I+II; liver; thymus; spleen; tissue concentrations of Zn; Ca; Mg and Fe

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