| First Author | Andreone T | Year | 2012 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 303 |
| Issue | 2 | Pages | E172-9 |
| PubMed ID | 22535743 | Mgi Jnum | J:187208 |
| Mgi Id | MGI:5435669 | Doi | 10.1152/ajpendo.00055.2012 |
| Citation | Andreone T, et al. (2012) Cytokine-mediated beta-cell damage in PARP-1-deficient islets. Am J Physiol Endocrinol Metab 303(2):E172-9 |
| abstractText | 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 beta-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 beta-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. |
