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Titolo:
Activation of Reg gene, a gene for insulin-producing beta-cell regeneration: Poly(ADP-ribose) polymerase binds Reg promoter and regulates the transcription by autopoly(ADP-ribosyl)ation
Autore:
Akiyama, T; Takasawa, S; Nata, K; Kobayashi, S; Abe, M; Shervani, NJ; Ikeda, T; Nakagawa, K; Unno, M; Matsuno, S; Okamoto, H;
Indirizzi:
Tohoku Univ, Grad Sch Med, Dept Biochem, Aoba Ku, Sendai, Miyagi 9808575, Japan Tohoku Univ Sendai Miyagi Japan 9808575 Ku, Sendai, Miyagi 9808575, Japan Tohoku Univ, Grad Sch Med, Dept Surg, Aoba Ku, Sendai, Miyagi 9808575, Japan Tohoku Univ Sendai Miyagi Japan 9808575 Ku, Sendai, Miyagi 9808575, Japan
Titolo Testata:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
fascicolo: 1, volume: 98, anno: 2001,
pagine: 48 - 53
SICI:
0027-8424(20010102)98:1<48:AORGAG>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
CYCLIC ADP-RIBOSE; LEUKOCYTE ANTIGEN CD38; DNA STRAND BREAKS; PANCREATIC-ISLETS; CHROMOSOMAL LOCALIZATION; SYNTHETASE INHIBITORS; PROINSULIN SYNTHESIS; PROTEIN; STREPTOZOTOCIN; EXPRESSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Okamoto, H Tohoku Univ, Grad Sch Med, Dept Biochem, Aoba Ku, 2-1 Seiryo Machi, Sendai, Miyagi 9808575, Japan Tohoku Univ 2-1 Seiryo Machi Sendai Miyagi Japan 9808575 Japan
Citazione:
T. Akiyama et al., "Activation of Reg gene, a gene for insulin-producing beta-cell regeneration: Poly(ADP-ribose) polymerase binds Reg promoter and regulates the transcription by autopoly(ADP-ribosyl)ation", P NAS US, 98(1), 2001, pp. 48-53

Abstract

The regeneration of pancreatic islet beta cells is important for the prevention and cure of diabetes mellitus. We have demonstrated that the administration of poly(ADP-ribose) synthetase/polymerase (PARP) inhibitors such as nicotinamide to 90% depancreatized rats induces islet regeneration. From the regenerating islet-derived cDNA library, we have isolated Reg (regenerating gene) and demonstrated that Reg protein induces beta -cell replication via the Reg receptor and ameliorates experimental diabetes. However, the mechanism by which Reg gene is activated in beta cells has been elusive. In this study, we found that the combined addition of IL-6 and dexamethasone induced the expression of Reg gene in beta cells and that PARP inhibitors enhanced the expression. Reporter gene assays revealed that the -81 approximateto -70 region (TGCCCCTCCCAT) of the Reg gene promoter is a cia-element forthe expression of Reg gene. Gel mobility shift assays showed that the active transcriptional DNA/protein complex was formed by the stimulation with IL-6 and dexamethasone. Surprisingly, PARP bound to the cis-element and was involved in the active transcriptional DNA/protein complex. The DNA/proteincomplex formation was inhibited depending on the autopoly(ADP-ribosyl)ation of PARP in the complex. Thus, PARP inhibitors enhance the DNA/protein complex formation for Reg gene transcription and stabilize the complex by inhibiting the autopoly(ADP-ribosyl)ation of PARP.

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Documento generato il 29/09/20 alle ore 09:41:13