Naslov
Metallothioneins as regulators of liver regeneration and fetal organogenesis

Autori
Jakovac, Hrvoje ; Grebić, Damir ; Mrakovčić-Šutić, Ines ; Radošević-Stašić, Biserka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Periodicum biologorum / Vitale B. - Zagreb : Hrvatsko prirodoslovno društvo, 2007, 156-156

Skup
5th Croatian Congress of Pharmacology and 2th Congress of Croatian Physiological Society

Mjesto i datum
Osijek, Hrvatska, 19.09.2007. - 22.09.2007

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
metallothioneins I/II; liver regeneration; syngeneic pregnancy; fetal organogenesis

Sažetak
Introduction: Metallothioneins (MTs), the intracellular, ubiquitous, low molecular cysteine rich proteins are stress-proteins, which participate in cell reactions on different kinds of injuries, as well as in host defense responses, affecting the functions of several immune cells, TLR signaling, expression of MHC proteins and co-stimulatory molecules on dendritic cells and the production and release of pro-inflammatory cytokines. Owing to this the induction MTs dramatically increases in response to tissue injury, infection, inflammation and neoplastic disease. It is however, of particular interest that both nuclear and cytoplasmic localization of MTs might be transiently expressed also in several growing tissues and during fetal development, implying that they might participate in DNA synthesis-and apoptosis-related processes, in regulation of transition from proliferation to the differentiation stage, as well as in several immune-related processes that initiate and coordinate the normal growth. In an attempt to underline the physiological functions of MTs in this study we analyzed the tissue distribution of MT I+II after partial hepatectomy (pHx), as well as in syngeneic pregnancy, looking for the changes in the liver, at the fetoplacental unit and in several fetal tissues. Material and methods: Experiments were done on C57/BL6 mice, which were subjected to 1/3 pHx or matted with syngeneic partner. Mice were sacrified in early postoperative period (1, 2, 6, 12 and 24 hours) after one-third hepatectomy (pHx), or on 16th day of syngeneic pregnancy. MT I/II expression was determined immunohistochemicaly, using monoclonal anti-MT I+II antibody and DAKO EnVision System. Additionally, in the regenerating liver MT-I mRNA and apoptosis were analyzed by RT-PCR and by TUNEL method, respectively. Results: The data have shown that fast liver growth after pHx is followed by marked increases of MT proteins and MT-I mRNA in the regenerating liver, where areas expressing cytoplasmic and nuclear MT immunoreactivity inversely correlated with those containing apoptotic cells. Similar over expression of MT I/II was found in maternal and fetal liver, as well as on the fetoplacental unit, affecting syncytiotrophoblast, cytotrophoblast, stromal and macrophages-like cells within the core of the chorionic vili and some decidual cells. Additionally, a high cytoplasmic and nuclear MT I/II imunoreactivity was noticed in fetal tissues, such as intestine, pancreas, gallbladder, kidneys and skin. Conclusion: The data underline the growth-related properties of MTs, implying that as metal-donors or metal-acceptors they alter the functional state of metal-dependent proteins, such as zinc finger domain-containing transcription factors, DNA synthesis enzymes and signal transduction molecules, regulating cell proliferation and apoptosis, facilitating also the flow of vital nutrient materials to the embryos and providing a barrier to entry of toxic materials from the mother at the fetoplacental unit. (Supported by grant 0621341-1337 from Croatian Ministry of Science).

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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