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001-es BibID:BIBFORM014283
Első szerző:Bai Péter (biokémikus)
Cím:Partial protection by poly(ADP-ribose) polymerase inhibitors from nitroxyl-induced cytotoxity in thymocytes / Bai Péter, Bakondi Edina, Szabó Éva, Gergely Pál, Szabo Csaba, Virág László
Dátum:2001
ISSN:0891-5849 (Print)
Megjegyzések:Nitroxyl (NO(-)/HNO), has been proposed to be one of the NO(*)-derived cytotoxic species. Although the biological effect of nitroxyl is largely unknown, it has been reported to cause DNA breakage and cytotoxicity. We have therefore investigated whether NO(-)/HNO-induced DNA single-strand breakage activates the nuclear nick sensor enzyme poly(ADP-ribose) polymerase (PARP) and whether PARP activation affects the mode of NO(-)/HNO- induced cell death. NO(-)/HNO generated from Angeli's salt (AS, sodium trioxodinitrate) (0-300 microM) induced DNA single-strand breakage, PARP activation, and a concentration-dependent cytotoxicity in murine thymocytes. AS-induced cell death was also accompanied by decreased mitochondrial membrane potential and increased secondary superoxide production. The cytotoxicity of AS, as measured by propidium iodide uptake, was abolished by electron acceptors potassium ferricyanide, TEMPOL, the intracellular calcium chelator BAPTA-AM, and by PARP inhibitors 3-aminobenzamide (3-AB) and PJ-34. The cytoprotective effect of 3-AB was paralleled by increased output of AS-induced apoptotic parameters such as phosphatidylserine exposure, caspase activation, and DNA fragmentation. No significant increase in tyrosine nitration could be observed in AS-treated thymocytes as opposed to peroxynitrite-treated cells, indicating that tyrosine nitration is not likely to contribute to NO(-)/HNO-induced cytotoxicity. Our results demonstrate that NO(-)/HNO-induced PARP activation shifts the default apoptotic cell death toward necrosis in thymocytes. However, as total PARP inhibition resulted only in 30% cytoprotection, PARP-independent mechanisms dominate NO(-)/HNO-induced cytotoxicity in thymocytes.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Animals
egyetemen (Magyarországon) készült közlemény
Apoptosis
Benzamides/ pharmacology
Caspases/metabolism
Cells, Cultured
DNA Damage/drug effects
DNA Fragmentation/drug effects
Enzyme Activation/drug effects/physiology
Enzyme Inhibitors/ pharmacology
Male
Mice
Mice, Inbred C57BL
Mitochondria/ drug effects
Nitrates
Nitrites/toxicity
Nitrogen Oxides/ toxicity
Poly(ADP-ribose) Polymerases/ antagonists & inhibitors/metabolism
Protective Agents/ pharmacology
Thymus Gland/cytology/ drug effects
Tyrosine
Megjelenés:Free radical biology and medicine. - 31 : 12 (2001), p. 1616-1623. -
További szerzők:Bakondi Edina (1975-) (biokémikus, vegyész) Szabó Éva (1965-) (bőrgyógyász, kozmetológus) Gergely Pál (1947-) (biokémikus) Szabó Csaba Virág László (1965-) (biokémikus, sejtbiológus, farmakológus)
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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