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dc.contributor.authorChoi, Won-Il
dc.contributor.authorKwon, Kun Young
dc.contributor.authorSeo, Jeong Wook
dc.contributor.authorBeagle, John
dc.contributor.authorQuinn, Deborah A.
dc.contributor.authorHales, Charles Albert
dc.date.accessioned2011-01-28T04:31:45Z
dc.date.issued2009
dc.identifier.citationChoi, Won-Il, Kun Young Kwon, Jeong Wook Seo, John Beagle, Deborah A Quinn and Charles A Hales. 2009. The role of phosphodiesterase 3 in endotoxin-induced acute kidney injury. BMC Infectious Diseases 9:80.en_US
dc.identifier.issn1471-2334en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4688284
dc.description.abstractBackground: Acute kidney injury frequently accompanies sepsis. Endotoxin is known to reduce tissue levels of cAMP and low levels of cAMP have been associated with renal injury. We, therefore, hypothesized that endotoxin induced renal injury by activating phosphodiesterase 3 (PDE3) which metabolizes cAMP and that amrinone an inhibitor of PDE3 would prevent the renal injury. Methods: Animals were divided into three groups (n = 7/group): 1) Control (0.9% NaCl infusion without LPS); 2) LPS (0.9% NaCl infusion with LPS); 3) Amrinone+LPS (Amrinone infusion with LPS). Either lipopolysaccharide (LPS) or vehicle was injected via the jugular vein and the rats followed for 3 hours. We explored the expression of PDE3 isoenzymes and the concentrations of cAMP in the tissue. Results: The PDE3B gene but not PDE3A was upregulated in the kidney of LPS group. Immunohistochemistry also showed that PDE3B was expressed in the distal tubule in the controls and LPS caused PDE3B expression in the proximal as well. However, PDE3A was not expressed in the kidney either in the control or LPS treated groups. Tissue level of cAMP was decreased after LPS and was associated with an increase in blood urea nitrogen, creatinine, ultrastructural proximal tubular changes, and expression of inducible nitric oxide synthase (iNOS) in the endotoxemic kidney. In septic animals the phosphodiesterase 3 inhibitor, amrinone, preserved the tissue cAMP level, renal structural changes, and attenuated the increased blood urea nitrogen, creatinine, and iNOS expression in the kidney. Conclusion: These findings suggest a significant role for PDE3B as an important mediator of LPS-induced acute kidney injury.en_US
dc.language.isoen_USen_US
dc.publisherBioMed Centralen_US
dc.relation.isversionofdoi:10.1186/1471-2334-9-80en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2694814/en_US
dash.licenseLAA
dc.subjectAcute-Renal-Failureen_US
dc.subjectNitric-Oxide Synthaseen_US
dc.subjectProximal Tubule Injuryen_US
dc.subjectIschemia/Reperfusion Injuryen_US
dc.titleThe role of phosphodiesterase 3 in endotoxin-induced acute kidney injuryen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalBMC Infectious Diseasesen_US
dash.depositing.authorHales, Charles Albert
dc.date.available2011-01-28T04:31:45Z
dash.affiliation.otherHMS^Medicine-Massachusetts General Hospitalen_US
dc.identifier.doi10.1186/1471-2334-9-80*
dash.contributor.affiliatedHales, Charles Albert


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