NR1 and NR3B Composed Intranuclear N-methyl-d-aspartate Receptor Complexes in Human Melanoma Cells

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PP2B and ERK1/2 regulate hyaluronan synthesis of HT168 and WM35 human melanoma cell lines

Hyaluronan (HA) is the major glycosaminoglycan component of the extracellular matrix in either normal or malignant tissues and it may affect proliferation, motility and differentiation of various cell types. Three isoforms of plasma membrane-bound hyaluronan synthases (HAS 1, 2 and 3) secrete and simultaneously bind pericellular HA. HAS enzymes are subjects of post-translational protein phosphorylation which is believed to regulate their enzymatic activity. In this study, we investigated the HA homeostasis of normal human epidermal melanocytes, HT168 and WM35 human melanoma cell lines and melanoma metastases. HAS2 and HAS3 were detected in all the samples, while the expression of HAS1 was not detectable in any case. Malignant tissue samples and melanoma cell lines contained extra- and intracellular HA abundantly but not normal melanocytes. Applying HA as a chemoattractant facilitated the migration of melanoma cells in Boyden chamber. The amount of HA was reduced upon the inhibition of calcineurin with cyclosporine A (CsA), while the inhibition of ERK1/2 with PD098059 elevated it in both cell lines. The signals of Ser/Thr phosphoproteins at 57 kD were stronger after CsA treatment, while a markedly weaker signal was detected upon inhibition of the MAPK pathway. Our results suggest opposing effects of the two investigated enzymes on the HA homeostasis of melanoma cells. We propose that the dephosphorylation of HAS enzymes targeted by PP2B augments HA production, while their phosphorylation by the activity of MAPK pathway reduces HA synthesis. As the expression of the HA receptor RHAMM was also significantly enhanced by PD098059, the MAPK pathway exerted a complex attenuating effect on HA signalling in the investigated melanoma cells. This observation suggests that the application of MAPK-ERK pathway inhibitors requires a careful therapeutic design in melanoma treatment

Régészeti kutatások Somogy megyében 2016–2017 között = Archaeological research in Somogy county between 2016-2017

Abstract: In the first half of the study excavation projects financed with the support of local governments and NKA (Bárdudvarnok, Iharos, Zamárdi) are described, in the second half the archeological results of the excavation connected to a development of Route No 67 and Route No 76 are related

A Drosophila melanogaster sejtes immunitása = The cellular immunity of Drosophila melanogaster

A Drosophila sejtközvetítette immunválaszának szabályozását vizsgáltuk valamint molekuláris immunológiai és genetikai ismeretek elsajátítását és projekt építését tettük lehetővé a tudomány iránt érdeklődő diákok és kutatók számára.Adult Drosophila vérsejtjeire, makrofágokra és a lamellocitákra jellemző markereket azonosítottunk.Az L5 antigén a lamellociták differenciálódásának a szuppresszora.A P1 antigénről (Nimród) megállapítottuk, hogy részt vesz a fagocitózisban.A P1 molekula jellegzetes motívumot hordoz (Nim-repeat),mely egy szupercsaládot határoz meg:tagjai a kódoló gén közvetlen környezetében helyezkednek el. Javaslatot tettünk a Nim repeat kialakulásának a modelljére,leírtuk a Nimród szuprcsalád lehetséges evolúcióját.A vérképzést és a vérsejtek funkcióit szabályozó géneket és molekulákat azonosítottunk.Egy epigenetikus regulátorról megállapítottuk,hogy a vérsejtek osztódását,egy mestergénről pedig,hogy a lamellociták differenciálódását szabályozza.RNSi mutánsgyűjteményben a szesszilis szövet kialakulásában résztvevő génterméket azonosítottunk.Megállapítottuk, hogy a lamellociták a szesszilis szövetből származnak,effektorsejtekké történő differenciálódásuk lépései immunológiai markerekkel nyomonkövethetők.Eddig nem ismert sejteket találtunk Drosophila fajokban és a jellemzésükre alkalmas immunológiai markereket azonosítottunk.Az általunk felismert markereket a Drosophila vérsejt-differenciálódását és funkcióit vizsgáló laboratóriumokban rutinszerűen használják. | We studied the regulation cellular immunity of Drosophila and developed a training-unit based on the research and teaching experience of our multidisciplinary team, with a broad interest in molecular immunology. Results: We identified markers for embryonic macrophages, lamellocytes and blood cells of the adult fly. We described the L5 antigen as a suppressor of lamellocyte development. We defined P1 antigen (Nimrod) as a phagocytosis receptor with a structurally and phylogenetically conserved characteristic unit, the Nim repeat. The repeat defines a superfamily with members located in the close proximity of the p1 gene. We suggested a model for the origin of the Nim repeat, and described the possible evolution of the superfamily. We defined an epigenetic regulator of blood cell differentiation and a master gene regulating the development of lamellocytes. We defined the sessile hematopoietic tissue as the source of lamellocytee precursors. We characterized sequential events in lamellocyte development from sessile stem cells to mature lamellocytes by sequential expression of lamellocyte antigens. We found so far undefined cell types in Drosophila species and developed immunological markers for them. The hemocyte markers defined in our laboratory are used worldwide routinely in studies of blood cell development and function in Drosophila