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001-es BibID:	BIBFORM001037
Első szerző:	Bai Péter (biokémikus)
Cím:	Protein tyrosine nitration and poly(ADP-ribose) polymerase activation in N-methyl-N-nitrosoguanidine-treated thymocytes : implication for cytotoxicity / Bai P., Hegedűs C., Erdélyi K., Szabó E., Bakondi E., Gergely S., Szabó C., Virág L.
Dátum:	2007
Megjegyzések:	1-Methyl-3-nitro-1-nitrosoguanidine (MNNG) is a DNA alkylating agent. DNA alkylation by MNNG is known to trigger accelerated poly(ADP-ribose) metabolism. Various nitroso compounds release nitric oxide (NO). Therefore, we set out to investigate whether MNNG functions as NO donor and whether MNNG-derived NO or secondary NO metabolites such as peroxynitrite contribute to MNNG-induced cytotoxicity. MNNG in aqueous solutions resulted in time- and concentration-dependent NO release and nitrite/nitrate formation. Moreover, various proteins in MNNG-treated thymocytes were found to be nitrated, indicating that MNNG-derived NO may combine with cellular superoxide to form peroxynitrite, a nitrating agent. MNNG also caused DNA breakage and increased poly(ADP-ribose) polymerase activity and cytotoxicity in thymocytes. MNNG-induced DNA damage (measured by the comet assay) and thymocyte death (measured by propidium iodide uptake) was prevented by the PARP inhibitor PJ-34 and by glutathione (GSH) or N-acetylcysteine (NAC). The cytoprotection provided by PJ-34 against necrotic parameters was paralleled by increased outputs in apoptotic parameters (caspase activity, DNA laddering) indicating that PARP activation diverts apoptotic death toward necrosis. As MNNG-induced cytotoxicity showed many similarities to peroxynitrite-induced cell death, we tested whether peroxynitrite was responsible for at least part of the cytotoxicity induced by MNNG. Cell-permeable enzymic antioxidants (superoxide dismutase and catalase), the NO scavenger cPTIO or the peroxynitrite decomposition catalyst FP15 failed to inhibit MNNG-induced DNA breakage and cytotoxicity. In conclusion, MNNG induces tyrosine nitration in thymocytes. Furthermore, MNNG damages DNA by a radical mechanism that does not involve NO or peroxynitrite.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban 1-methyl-3-nitro-1-nitrosoguanidine peroxynitrite egyetemen (Magyarországon) készült közlemény poly(ADP-ribose) polymerase necrosis apoptosis nitric oxide
Megjelenés:	Toxicology Letters. - 170 : 3 (2007), p. 203-213. -
További szerzők:	Hegedűs Csaba (1980-) (biokémikus, molekuláris biológus) Erdélyi Katalin (1978-) (molekuláris biológus, biokémikus) Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Bakondi Edina (1975-) (biokémikus, vegyész) Gergely Szabolcs (1977-) (kardiológus) Szabó Csaba Virág László (1965-) (biokémikus, sejtbiológus, farmakológus)
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