9 research outputs found
Genotoxikus hatásra bekövetkező funkcionális és strukturális DNS változások = Functional and structural changes in DNA upon genotoxic effects
MorfolĂłgiai Ă©s biokĂ©miai vizsgálataink arra utalnak, hogy a a genotoxikus hatások kategorizálhatĂłk az okozott kromatin változások alapján. A kemotoxikus változások potenciális diagnosztikus jelentĹ‘sĂ©ge miatt vizsgáltuk a nehĂ©zfĂ©mek (elsĹ‘sosrban kadmium) (Banfalvi et al., 2005), a gamma sugárzás (Nagy et al., 2004), az UVB sugárzás (Ujvárosi et al., 2007) Ă©s a carcinogĂ©n (dimetilnitrĂłzamin) hatására bekövetkezĹ‘ kromatin változásokat (TrencsĂ©nyi et al., 2007). Kadmium kezelĂ©s jellegzetes szakadásokat Ă©s nagy lyukakat hozott lĂ©tre a sejtmagban. A gamma sugárzás preapoptotikus hatására: a. a sejtek Ă©s sejtmagok mĂ©rete megnĹ‘tt, b. DNA tartalmuk a sejtciklus minden szakaszában kisebb volt a normál kezeletlen populáciĂłhoz kĂ©pest, c. a sejtciklus a korai S fázisban leállt (2,4 C Ă©rtĂ©knĂ©l), d. a kromatin kondenzálás annak fibrilláris szakaszában akadt el, e. az apoptotikus testek száma Ă©s nagysága a sejtciklus haladásávalfordĂtva arányos: sok aprĂł apoptotikus testtel az S fázis elejĂ©n Ă©s kevĂ©s nagy apoptotikus testtel az S fázis vĂ©gĂ©n. A CHO sejtekben mĂ©rt vizsgálatokat humán K562 sejteken megerĹ‘sĂtettĂĽk. UVB sugárzás hatására a kromoszĂłmák nem voltak láthatĂłk, a sĂ©rĂĽlĂ©s hatására vĂ©kony összefĂĽggĹ‘ kromatin fátyol vonta be mind az interfázisos, mind a metafázisos kromoszĂłmákat. | Morphological and biochemical studies after genotoxic treatments suggest that the consequences of various chromatin injuries can be categorized based on the assessment of injury-specific chromatin changes. Due to its diagnostic significance, we have started to determine and systematize the effects of heavy metals, primarily cadmium treatment (Banfalvi et al., 2005), gamma irradiation (Nagy et al., 2004) and UV irradiation (Ujvarosi et al., 2007). After cadmium treatment and have seen the same large extensive disruptions and holes in the nuclear membrane and sticky incompletely folded chromosomes typical for cadmium treatment (Nagy et al., 2004; Banfalvi et al., 2007). Preapoptotic changes upon Îł-irradiation manifested as: (a) The cellular and nuclear sizes increased. (b) The DNA content was lower in each elutriated subpopulation of cells. (c) The progression of the cell cycle was arrested in the early S phase at 2.4 C value. (d) The chromatin condensation was blocked at its fibrillary stage. (e) The number and size of apoptotic bodies were inversely correlated with the progression of the cell cycle, with many small apoptotic bodies in early S phase and less but larger apoptotic bodies in late S phase (Nagy et al., 2004). Similar observations were made in K562 cells (Banfalvi et al., 2007). UV irradiation blocked chromatin condensation at its fibrillary stage, nuclear structures were blurred and covered with fibrillary chromatin, neither interphase nor metaphase chromosomes were visible
Composition and function of macroencapsulated human embryonic stem cell-derived implants: comparison with clinical human islet cell grafts
Inactivity of Recombinant ELA2B Provides a New Example of Evolutionary Elastase Silencing in Humans
Human mesotrypsin exhibits restricted S1' subsite specificity with a strong preference for small polar side chains
Expression of human cationic trypsinogen with an authentic N terminus using intein-mediated splicing in aminopeptidase P deficient Escherichia coli
A degradation-sensitive anionic trypsinogen (PRSS2) variant protects against chronic pancreatitis.
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51133.pdf (publisher's version ) (Closed access)Chronic pancreatitis is a common inflammatory disease of the pancreas. Mutations in the genes encoding cationic trypsinogen (PRSS1) and the pancreatic secretory trypsin inhibitor (SPINK1) are associated with chronic pancreatitis. Because increased proteolytic activity owing to mutated PRSS1 enhances the risk for chronic pancreatitis, mutations in the gene encoding anionic trypsinogen (PRSS2) may also predispose to disease. Here we analyzed PRSS2 in individuals with chronic pancreatitis and controls and found, to our surprise, that a variant of codon 191 (G191R) is overrepresented in control subjects: G191R was present in 220/6,459 (3.4%) controls but in only 32/2,466 (1.3%) affected individuals (odds ratio 0.37; P = 1.1 x 10(-8)). Upon activation by enterokinase or trypsin, purified recombinant G191R protein showed a complete loss of trypsin activity owing to the introduction of a new tryptic cleavage site that renders the enzyme hypersensitive to autocatalytic proteolysis. In conclusion, the G191R variant of PRSS2 mitigates intrapancreatic trypsin activity and thereby protects against chronic pancreatitis