Mouse mammary tumor virus gene expression is suppressed by oligomeric ellagitannins, novel inhibitors of poly(ADP-ribose) glycohydrolase

Yan Jyu Tsai, Tsutomu Aoki, Hideharu Maruta, Hideaki Abe, Hiroshi Sakagami, Tsutomu Hatano, Takuo Okuda, Sei Ichi Tanuma

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

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 341 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 341 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 depoly(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.

Original languageEnglish
Pages (from-to)14436-14442
Number of pages7
JournalJournal of Biological Chemistry
Volume267
Issue number20
Publication statusPublished - Jul 15 1992

Fingerprint

Hydrolyzable Tannins
Mouse mammary tumor virus
Viruses
Gene expression
Glucocorticoids
Tumors
Gene Expression
Adenosine Diphosphate
HMGN2 Protein
HMGN1 Protein
Transcription
Poly Adenosine Diphosphate Ribose
Histones
Dimers
poly ADP-ribose glycohydrolase
Proteins
Genes
Breast Neoplasms
Messenger RNA
Molecules

ASJC Scopus subject areas

  • Biochemistry

Cite this

Mouse mammary tumor virus gene expression is suppressed by oligomeric ellagitannins, novel inhibitors of poly(ADP-ribose) glycohydrolase. / Tsai, Yan Jyu; Aoki, Tsutomu; Maruta, Hideharu; Abe, Hideaki; Sakagami, Hiroshi; Hatano, Tsutomu; Okuda, Takuo; Tanuma, Sei Ichi.

In: Journal of Biological Chemistry, Vol. 267, No. 20, 15.07.1992, p. 14436-14442.

Research output: Contribution to journalArticle

Tsai, YJ, Aoki, T, Maruta, H, Abe, H, Sakagami, H, Hatano, T, Okuda, T & Tanuma, SI 1992, 'Mouse mammary tumor virus gene expression is suppressed by oligomeric ellagitannins, novel inhibitors of poly(ADP-ribose) glycohydrolase', Journal of Biological Chemistry, vol. 267, no. 20, pp. 14436-14442.
Tsai, Yan Jyu ; Aoki, Tsutomu ; Maruta, Hideharu ; Abe, Hideaki ; Sakagami, Hiroshi ; Hatano, Tsutomu ; Okuda, Takuo ; Tanuma, Sei Ichi. / Mouse mammary tumor virus gene expression is suppressed by oligomeric ellagitannins, novel inhibitors of poly(ADP-ribose) glycohydrolase. In: Journal of Biological Chemistry. 1992 ; Vol. 267, No. 20. pp. 14436-14442.
@article{67460bbb9cbf400d9420812dca71425a,
title = "Mouse mammary tumor virus gene expression is suppressed by oligomeric ellagitannins, novel inhibitors of poly(ADP-ribose) glycohydrolase",
abstract = "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 341 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 341 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 depoly(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.",
author = "Tsai, {Yan Jyu} and Tsutomu Aoki and Hideharu Maruta and Hideaki Abe and Hiroshi Sakagami and Tsutomu Hatano and Takuo Okuda and Tanuma, {Sei Ichi}",
year = "1992",
month = "7",
day = "15",
language = "English",
volume = "267",
pages = "14436--14442",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "20",

}

TY - JOUR

T1 - Mouse mammary tumor virus gene expression is suppressed by oligomeric ellagitannins, novel inhibitors of poly(ADP-ribose) glycohydrolase

AU - Tsai, Yan Jyu

AU - Aoki, Tsutomu

AU - Maruta, Hideharu

AU - Abe, Hideaki

AU - Sakagami, Hiroshi

AU - Hatano, Tsutomu

AU - Okuda, Takuo

AU - Tanuma, Sei Ichi

PY - 1992/7/15

Y1 - 1992/7/15

N2 - 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 341 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 341 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 depoly(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.

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 341 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 341 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 depoly(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.

UR - http://www.scopus.com/inward/record.url?scp=0026681651&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026681651&partnerID=8YFLogxK

M3 - Article

VL - 267

SP - 14436

EP - 14442

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 20

ER -