PMID- 1321148 OWN - NLM STAT- MEDLINE DCOM- 19920814 LR - 20210210 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 267 IP - 20 DP - 1992 Jul 15 TI - Mouse mammary tumor virus gene expression is suppressed by oligomeric ellagitannins, novel inhibitors of poly(ADP-ribose) glycohydrolase. PG - 14436-42 AB - Oligomeric ellagitannins (nobotanins B, E, and K) were found to be potent inhibitors of poly(ADP-ribose) glycohydrolase purified from mouse mammary tumor 34I cells. Kinetic analysis revealed that the inhibition of nobotanin B (dimer) was competitive with respect to the substrate poly(ADP-ribose), whereas nobotanin E (trimer) and nobotanin K (tetramer) exhibited mixed-type inhibition. These results suggest that the dimeric structure of ellagitannin may have a functional domain that competes with poly(ADP-ribose) on the poly(ADP-ribose) glycohydrolase molecule. To determine the inhibitory effects of oligomeric ellagitannins on poly(ADP-ribose) glycohydrolase in vivo, we examined their effects on de-poly(ADP-ribosyl)ation of some chromosomal proteins in intact 34I cells that was induced by glucocorticoid treatment. Nobotanin B caused concentration-dependent inhibition of glucocorticoid-induced de-poly(ADP-ribosyl)ation of HMG 14 and 17 and histone H1 in intact 34I cells. Interestingly, this inhibition was associated with suppression of the glucocorticoid-sensitive mouse mammary tumor virus (MMTV) mRNA synthesis. In contrast, nobotanin E and K had little inhibitory effect on either de-poly(ADP-ribosyl)ation of these proteins or induction of MMTV transcription after glucocorticoid treatment. Nobotanin B but not E and K was taken into 34I cells. These results may suggest that the suppression of glucocorticoid-sensitive MMTV transcription results from in vivo inhibition of poly(ADP-ribose) glycohydrolase by nobotanin B. These results also indicate the importance of de-poly(ADP-ribosyl)ation of HMG 14 and 17 and histone H1 in regulation of transcription of the glucocorticoid-sensitive MMTV gene. FAU - Tsai, Y J AU - Tsai YJ AD - Department of Pharmacology, Faculty of Medical Sciences, Taipei Medical College, Taiwan, Republic of China. FAU - Aoki, T AU - Aoki T FAU - Maruta, H AU - Maruta H FAU - Abe, H AU - Abe H FAU - Sakagami, H AU - Sakagami H FAU - Hatano, T AU - Hatano T FAU - Okuda, T AU - Okuda T FAU - Tanuma, S AU - Tanuma S LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Hydrolyzable Tannins) RN - 0 (Tannins) RN - 104696-16-4 (nobotanin B) RN - 113866-94-7 (nobotanin E) RN - 119683-39-5 (nobotanin K) RN - EC 3.2.1.- (Glycoside Hydrolases) RN - EC 3.2.1.143 (poly ADP-ribose glycohydrolase) SB - IM MH - Animals MH - Binding, Competitive MH - Cell Nucleus/enzymology MH - Gene Expression/drug effects MH - Gene Expression Regulation, Viral/drug effects MH - Genes, Viral/drug effects MH - Glycoside Hydrolases/*antagonists & inhibitors/isolation & purification MH - *Hydrolyzable Tannins MH - Kinetics MH - Mammary Neoplasms, Experimental MH - Mammary Tumor Virus, Mouse/drug effects/*genetics MH - Mice MH - Mice, Inbred C3H MH - Molecular Structure MH - Structure-Activity Relationship MH - Tannins/*pharmacology MH - *Transcription, Genetic MH - Tumor Cells, Cultured EDAT- 1992/07/15 00:00 MHDA- 1992/07/15 00:01 CRDT- 1992/07/15 00:00 PHST- 1992/07/15 00:00 [pubmed] PHST- 1992/07/15 00:01 [medline] PHST- 1992/07/15 00:00 [entrez] AID - S0021-9258(19)49731-7 [pii] PST - ppublish SO - J Biol Chem. 1992 Jul 15;267(20):14436-42.