title: Influence of histone acetylation on the modification of cytoplasmic and nuclear proteins by ADP-ribosylation in response to free radicals.
abstract: Inhibition of histone deacetylase by addition of 5 mM n-sodium butyrate to the growth medium increases the utilization of [32P]NAD+ and ADP-ribosylation (ADPR) of total cellular proteins of V79, HeLa, mouse B16, mouse Fib/T and human T1 kidney cells by a factor of 1.2-2.3. When the ADP-ribosylase is challenged by exposing cells to damage by .OH radicals (25 microM CuSO4 2.8 mM H2O2) ADPR increases by factors of 5.7-6.0 and 3.2-4.0 in normal and butyrated cells, respectively. Operation of the free radical generator is supported by the response to EDTA and radical scavengers. Densitometric analysis of autoradiographs from SDS-gels show that butyrate exposure increases basal ADPR-modification of histones from T1 cells by factors of 1.1-1.9. Addition of .OH radicals increases the ADPR modifications of histones 4.4-8.7-fold in normal cells and 3.2-6.7-fold in butyrate exposed cells. Butyrate exposure elevates base level ADPR-modification and reduces subsequent ADPR-modification initiated by DNA damage. The results are consistent with the view that ADPR-modification and histone acetylation have overlapping functions and probably induce similar structural changes in chromatin.
authors.affiliation: Department of Radiotherapy, Faculty of Medicine, University of Stellenbosch, Tygerberg, South Africa. elb@maties.sun.ac.za
authors.forename: L
authors.initials: L
authors.lastname: Böhm
authors.forename: F A
authors.initials: FA
authors.lastname: Schneeweiss
authors.forename: R N
authors.initials: RN
authors.lastname: Sharan
authors.forename: L E
authors.initials: LE
authors.lastname: Feinendegen
mesh_terms: D000107:Acetylation; D002087:Butyrates; D020148:Butyric Acid; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D005609:Free Radicals / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*
chemical_list: D002087:Butyrates; D005609:Free Radicals; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D009687:Nuclear Proteins; D020148:Butyric Acid; D011065:Poly(ADP-ribose) Polymerases