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 synovi al fibroblasts after treatment with active oxygen released by xanthine /xanthine oxidase is inhibited by addition of 1 and 10 mu M 4-hydroxy- 2,3-trans-nonenal (HNE). The endogenous formation of HNE by the xanthi ne/xanthine oxidase system is not responsible for the inhibitory effec t of the aldehyde, owing to the low accumulation rate of the lipid per oxidation product in the system used. HNE is able to inhibit the isola ted nuclear enzyme ADP-ribosyltransferase, as shown by an in vitro ass ay with an K-i of 4 mu mol/litre. Therefore the molecular basis of HNE -mediated effects on cell proliferation, differentiation and transform ation might be due to the inhibitory effect of poly(ADP-ribos)ylation.