Inhibition of poly(ADP-ribose) formation by 4-hydroxynonenal in primary cultures of rabbit synovial fibroblasts.
The formation of poly(ADP-ribose) in primary cultures of rabbit synovial fibroblasts after treatment with active oxygen released by xanthine/xanthine oxidase is inhibited by addition of 1 and 10 microM 4-hydroxy-2,3-trans-nonenal (HNE). The endogenous formation of HNE by the xanthine/xanthine oxidase system is not responsible for the inhibitory effect of the aldehyde, owing to the low accumulation rate of the lipid peroxidation product in the system used. HNE is able to inhibit the isolated nuclear enzyme ADP-ribosyltransferase, as shown by an in vitro assay with an Ki of 4 mumol/litre. Therefore the molecular basis of HNE-mediated effects on cell proliferation, differentiation and transformation might be due to the inhibitory effect of poly(ADP-ribos)ylation.
Ullrich
O
O
Clinic of Physical Therapy, Medical Faculty (Charité), Humboldt University Berlin, Federal Republic of Germany.
Siems
W G
WG
Lehmann
K
K
Huser
H
H
Ehrlich
W
W
Grune
T
T
D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D011064:Poly Adenosine Diphosphate Ribose / Q000096:biosynthesis*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism; D019820:Xanthine; D014969:Xanthine Oxidase / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D000447:Aldehydes; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D017382:Reactive Oxygen Species; D014970:Xanthines; D019820:Xanthine; D011064:Poly Adenosine Diphosphate Ribose; D014969:Xanthine Oxidase; C027576:4-hydroxy-2-nonenal