Linked Life Data

21289052

Source:http://linkedlifedata.com/resource/pubmed/id/21289052

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-5-5
pubmed:abstractText
Ischemic acute kidney injury (AKI) triggers expression of adaptive (protective) and maladaptive genes. Agents that increase expression of protective genes should provide a therapeutic benefit. We now report that bardoxolone methyl (BARD) ameliorates ischemic murine AKI as assessed by both renal function and pathology. BARD may exert its beneficial effect by increasing expression of genes previously shown to protect against ischemic AKI, NF-E2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor-? (PPAR?), and heme oxygenase 1 (HO-1). Although we found that BARD alone or ischemia-reperfusion alone increased expression of these genes, the greatest increase occurred after the combination of both ischemia-reperfusion and BARD. BARD had a different mode of action than other agents that regulate PPAR? and Nrf2. Thus we report that BARD regulates PPAR?, not by acting as a ligand but by increasing the amount of PPAR? mRNA and protein. This should increase ligand-independent effects of PPAR?. Similarly, BARD increased Nrf2 mRNA; this increased Nrf2 protein by mechanisms in addition to the prolongation of Nrf2 protein half-life previously reported. Finally, we localized expression of these protective genes after ischemia and BARD treatment. Using double-immunofluorescence staining for CD31 and Nrf2 or PPAR?, we found increased Nrf2 and PPAR? on glomerular endothelia in the cortex; Nrf2 was also present on cortical peritubular capillaries. In contrast, HO-1 was localized to different cells, i.e., tubules and interstitial leukocytes. Although Nrf2-dependent increases in HO-1 have been described, our data suggest that BARD's effects on tubular and leukocyte HO-1 during ischemic AKI may be Nrf2 independent. We also found that BARD ameliorated cisplatin nephrotoxicity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1522-1466
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
300
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
F1180-92
pubmed:meshHeading
pubmed-meshheading:21289052-Acute Kidney Injury, pubmed-meshheading:21289052-Analysis of Variance, pubmed-meshheading:21289052-Animals, pubmed-meshheading:21289052-Capillaries, pubmed-meshheading:21289052-Cisplatin, pubmed-meshheading:21289052-Disease Models, Animal, pubmed-meshheading:21289052-Fluorescent Antibody Technique, pubmed-meshheading:21289052-Heme Oxygenase-1, pubmed-meshheading:21289052-Ischemia, pubmed-meshheading:21289052-Kidney, pubmed-meshheading:21289052-Male, pubmed-meshheading:21289052-Membrane Proteins, pubmed-meshheading:21289052-Mice, pubmed-meshheading:21289052-Mice, Inbred C57BL, pubmed-meshheading:21289052-NF-E2-Related Factor 2, pubmed-meshheading:21289052-Oleanolic Acid, pubmed-meshheading:21289052-PPAR gamma, pubmed-meshheading:21289052-RNA, Messenger, pubmed-meshheading:21289052-Time Factors, pubmed-meshheading:21289052-Up-Regulation
pubmed:year
2011
pubmed:articleTitle
Bardoxolone methyl (BARD) ameliorates ischemic AKI and increases expression of protective genes Nrf2, PPAR?, and HO-1.
pubmed:affiliation
Department of Internal Medicine, Nephrology Division, UT Southwestern Medical Center, Dallas, TX 75390-8856, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural