RGD Reference Report - PARP mediates structural alterations in diabetic cardiomyopathy. - Rat Genome Database

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PARP mediates structural alterations in diabetic cardiomyopathy.

Authors: Chiu, J  Farhangkhoee, H  Xu, BY  Chen, S  George, B  Chakrabarti, S 
Citation: Chiu J, etal., J Mol Cell Cardiol. 2008 Sep;45(3):385-93. Epub 2008 Jul 8.
RGD ID: 2312287
Pubmed: PMID:18657544   (View Abstract at PubMed)
DOI: DOI:10.1016/j.yjmcc.2008.06.009   (Journal Full-text)

Diabetic cardiomyopathy is characterized by structural alterations such as cardiomyocyte hypertrophy, necrosis and focal fibrosis. Hyperglycemia-induced oxidative damage may play an important role in this pathogenetic process. Recent studies have shown that poly (ADP-ribose) polymerase (PARP) is activated in response to oxidative stress and cellular damage as well, plays a role in gene expression. This study investigated mechanisms of diabetes-induced, PARP-mediated development of structural alterations in the heart. Two models of diabetic complications were used to determine the role of PARP in oxidative stress, cardiac hypertrophy and fibrosis in the heart. PARP-1 knockout (PARP(-/-)) mice and their respective controls were fed a 30% galactose diet while male Sprague-Dawley rats were injected with streptozotocin and subsequently treated with PARP inhibitor 3-aminobenzamide (ABA). The in vivo experiments were verified in in vitro models which utilized both neonatal cardiomyocytes and endothelial cells. Our results indicate that hyperhexosemia caused upregulation of extracellular matrix proteins in association with increased transcriptional co-activator p300 levels, cardiomyocyte hypertrophy and increased oxidative stress. These pathogenetic changes were not observed in the PARP(-/-) mice and diabetic rats treated with ABA. Furthermore, these changes appear to be influenced by histone deacetylases. Similar results were obtained in isolated cardiomyocytes and endothelial cells. This study has elucidated for the first time a PARP-dependent, p300-associated pathway mediating the development of structural alterations in the diabetic heart.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Diabetes Mellitus  ISOEp300 (Rattus norvegicus)2312287; 2312287mRNA:increased expression:heart (rat)RGD 
Experimental Diabetes Mellitus  IEP 2312287mRNA:increased expression:heart (rat)RGD 
Experimental Diabetes Mellitus  ISOParp1 (Mus musculus)2312287; 2312287 RGD 
Experimental Diabetes Mellitus  IMP 2312287 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ep300  (E1A binding protein p300)
Parp1  (poly (ADP-ribose) polymerase 1)

Genes (Mus musculus)
Ep300  (E1A binding protein p300)
Parp1  (poly (ADP-ribose) polymerase family, member 1)

Genes (Homo sapiens)
EP300  (E1A binding protein p300)
PARP1  (poly(ADP-ribose) polymerase 1)


Additional Information