02 May 2003
Reg (Regenerating Gene) expression by PARP and NF-kB
H. Okamoto, T. Akiyama, K. Nata, T. Ikeda, N. Shervani, S. Kawaguchi, A. Yamauchi, T. Onogawa, N. Noguchi, S. TakasawaMed Sci Monit 2003; 9(1): 50-0 :: ID: 15113
Abstract
In 1981, we proposed that maintenance of the cellular NAD level in b-cells of pancreatic islets is essential for the synthesis and secretion of insulin and for the repair of b-cell injuries, and presented a unifying model for b-cell damage and its prevention (The Okamoto model), in which PARP activation plays an essential role in the depletion of NAD. In 1984, we demonstrated that the administration of PARP inhibitors to 90% depancreatized rats induces islet b-cell regeneration. From the regenerating islet-derived cDNA library we isolated Reg (Regenerating Gene) and demonstrated that Reg protein produced by Reg induces b-cell replication via the Reg receptor and ameliorates experimental diabetes. Recently, we showed that the combined addition of IL-6 and dexamethasone (Dx) induces the Reg gene expression in b-cells and that PARP inhibitors enhance the expression. PARP bound to the cis-element of Reg promoter and formed the active transcriptional DNA/protein complex upon stimulation by IL-6 and Dx. The formation was inhibited depending on the autopoly(ADP-ribosyl)ation of PARP in the complex and by the addition of an antibody against NF-kB. Overexpression of a mutated form of IkB with a serine-to-alanine mutation at residues 32 and 36 as well as the addition of inhibitors for IkB kinase abrogated the Reg gene transcription in response to IL-6/Dx stimulation. Thus, PARP forms the complex for Reg gene transcription with NF-kB. Therefore, the NF-kB activation as well as PARP inhibition could be new therapeutic approaches for b-cell regeneration.
Keywords: pancreatic b-cells, Okamoto model, Necrosis, Reg, Regeneration, NF-kB
Editorial
01 April 2024 : Editorial
Editorial: Forty Years of Waiting for Prevention and Cure of HIV Infection – Ongoing Challenges and Hopes for Vaccine Development and Overcoming Antiretroviral Drug ResistanceDOI: 10.12659/MSM.944600
Med Sci Monit 2024; 30:e944600
In Press
05 Mar 2024 : Clinical Research
Effects of Thermal Insulation on Recovery and Comfort of Patients Undergoing Holmium Laser LithotripsyMed Sci Monit In Press; DOI: 10.12659/MSM.942836
05 Mar 2024 : Clinical Research
Role of Critical Shoulder Angle in Degenerative Type Rotator Cuff Tears: A Turkish Cohort StudyMed Sci Monit In Press; DOI: 10.12659/MSM.943703
06 Mar 2024 : Clinical Research
Comparison of Outcomes between Single-Level and Double-Level Corpectomy in Thoracolumbar Reconstruction: A ...Med Sci Monit In Press; DOI: 10.12659/MSM.943797
21 Mar 2024 : Meta-Analysis
Economic Evaluation of COVID-19 Screening Tests and Surveillance Strategies in Low-Income, Middle-Income, a...Med Sci Monit In Press; DOI: 10.12659/MSM.943863
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952