Modulation of PARP-1 and PARP-2 expression by L-carnosine and trehalose after LPS and INFγ-induced oxidative stress.
Poly(ADP-ribose) polymerases (PARPs) play a crucial role in DNA damage surveillance through their nick sensor functions. Since PARPs' over activation leads to an excessive consumption of NAD(+) and ATP depletion, these enzymes also are involved in the early events of programmed cell death as well as in necrosis. In order to verify the protective action of L: -carnosine and trehalose against NO induced cell death, in the present study we examined their effects on the expression of PARP-1, PARP-2 and iNOS in primary rat astrocyte and oligodendrocyte cells, treated with lipopolysaccharide (LPS) and interferon gamma (INFγ), through semi-quantitative PCR and western analysis. To further characterize the molecular mechanisms underlying L-carnosine and trehalose action, we measured cell viability, nitrite production and LDH release. The data obtained clearly demonstrate that in the stress model employed L-carnosine and trehalose down regulate PARP-1 and PARP-2 expression in both cell phenotypes, thus suggesting their possible application in clinical trials.
Department of Chemical Sciences, Section of Biochemistry and Molecular Biology, Medical Faculty, University of Catania, Viale A Doria 6, 95125 Catania, Italy. spinavit@unict.it
Vittoria
V
Spina-Purrello
Salvatrice
S
Giliberto
Vincenza
V
Barresi
Vincenzo G
VG
Nicoletti
Anna Maria
AM
Giuffrida Stella
Enrico
E
Rizzarelli
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001483:Base Sequence; D015153:Blotting, Western; D002336:Carnosine / Q000494:pharmacology*; D002478:Cells, Cultured; D017931:DNA Primers; D007371:Interferon-gamma / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D051381:Rats; D014199:Trehalose / Q000494:pharmacology*
D017931:DNA Primers; D008070:Lipopolysaccharides; D007371:Interferon-gamma; D002336:Carnosine; D014199:Trehalose; C499322:Parp1 protein, rat; C557783:Parp2 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases