Linked Life Data

14988256

Source:http://linkedlifedata.com/resource/pubmed/id/14988256

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-2-27
pubmed:abstractText
Oxidative and nitrosative stress play a key role in the pathogenesis of diabetic neuropathy, but the mechanisms remain unidentified. Here we provide evidence that poly(ADP-ribose) polymerase (PARP) activation, a downstream effector of oxidant-induced DNA damage, is an obligatory step in functional and metabolic changes in the diabetic nerve. PARP-deficient (PARP(-/-)) mice were protected from both diabetic and galactose-induced motor and sensory nerve conduction slowing and nerve energy failure that were clearly manifest in the wild-type (PARP(+/+)) diabetic or galactose-fed mice. Two structurally unrelated PARP inhibitors, 3-aminobenzamide and 1,5-isoquinolinediol, reversed established nerve blood flow and conduction deficits and energy failure in streptozotocin-induced diabetic rats. Sciatic nerve immunohistochemistry revealed enhanced poly(ADP-ribosyl)ation in all experimental groups manifesting neuropathic changes. Poly(ADP-ribose) accumulation was localized in both endothelial and Schwann cells. Thus, the current work identifies PARP activation as an important mechanism in diabetic neuropathy and provides the first evidence for the potential therapeutic value of PARP inhibitors in this devastating complication of diabetes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0012-1797
pubmed:author
pubmed:issnType
Print
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
711-20
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Role of poly(ADP-ribose) polymerase activation in diabetic neuropathy.
pubmed:affiliation
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, USA. iobrosso@umich.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't