Cytokine-mediated β-cell damage in PARP-1-deficient islets. Am J Physiol Endocrinol Metab 2012 Jul 15;303(2):E172-9
Date
04/27/2012Pubmed ID
22535743Pubmed Central ID
PMC3431132DOI
10.1152/ajpendo.00055.2012Scopus ID
2-s2.0-84863897429 (requires institutional sign-in at Scopus site) 19 CitationsAbstract
Poly(ADP)-ribose polymerase (PARP) is an abundant nuclear protein that is activated by DNA damage; once active, it modifies nuclear proteins through attachment of poly(ADP)-ribose units derived from β-nicotinamide adenine dinucleotide (NAD(+)). In mice, the deletion of PARP-1 attenuates tissue injury in a number of animal models of human disease, including streptozotocin-induced diabetes. Also, inflammatory cell signaling and inflammatory gene expression are attenuated in macrophages isolated from endotoxin-treated PARP-1-deficient mice. In this study, the effects of PARP-1 deletion on cytokine-mediated β-cell damage and macrophage activation were evaluated. There are no defects in inflammatory mediator signaling or inflammatory gene expression in macrophages and islets isolated from PARP-1-deficient mice. While PARP-1 deficiency protects islets against cytokine-induced islet cell death as measured by biochemical assays of membrane polarization, the genetic absence of PARP-1 does not effect cytokine-induced inhibition of insulin secretion or cytokine-induced DNA damage in islets. While PARP-1 deficiency appears to provide protection from cell death, it fails to provide protection against the inhibitory actions of cytokines on insulin secretion or the damaging actions on islet DNA integrity.
Author List
Andreone T, Meares GP, Hughes KJ, Hansen PA, Corbett JAAuthor
John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsApoptosis
Cells, Cultured
Cytokines
DNA Damage
Female
Gene Deletion
Gene Expression
Insulin
Insulin-Secreting Cells
Macrophage Activation
Macrophages
Male
Membrane Potentials
Mice
Poly (ADP-Ribose) Polymerase-1
Poly(ADP-ribose) Polymerases
Signal Transduction
