| Induction of hemeoxygenase-1 reduces glomerular injury and apoptosis in diabetic spontaneously hypertensive rats. | |
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MedLine Citation:
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PMID: 22205229 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Induction of hemeoxygenase-1 (HO-1) lowers blood pressure and reduces organ damage in hypertensive animal models; however, a potential protective role for HO-1 induction against diabetic-induced glomerular injury remains unclear. We hypothesize that HO-1 induction will protect against diabetes-induced glomerular injury by maintaining glomerular integrity and inhibiting renal apoptosis, inflammation and oxidative stress. Diabetes was induced with streptozotocin in spontaneously hypertensive rats (SHR) as a model where the coexistence of hypertension and diabetes aggravates the progression of diabetic renal injury. Control and diabetic SHR were randomized to receive vehicle or the HO-1 inducer, cobalt protoporphyrin (CoPP). Glomerular albumin permeability was significantly greater in diabetic SHR compared to control, consistent with an increase in apoptosis and decreased glomerular nephrin and α3β1 integrin protein expression in diabetic SHR. CoPP significantly reduced albumin permeability and apoptosis and restored nephrin and α3β1 integrin protein expression levels in diabetic SHR. Glomerular injury in diabetic SHR was also associated with increases in NFκB induced-inflammation and oxidative stress relative to vehicle treated SHR and CoPP significantly blunted diabetes-induced increases in glomerular inflammation and oxidative stress in diabetic SHR. These effects were specific to exogenous stimulation of HO-1, since incubation with the HO inhibitor stannous mesoporphyrin alone did not alter glomerular inflammatory markers or oxidative stress yet was able to prevent CoPP mediated decreases in these parameters. These data suggest that induction of HO-1 reduces diabetic induced-glomerular injury and apoptosis and these effects are associated with decreased NFκB induced-inflammation and oxidative stress. |
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Authors:
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Ahmed A Elmarakby; Jessica Faulkner; Babak Baban; Mohamed A Saleh; Jennifer C Sullivan |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-28 |
Journal Detail:
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Title: American journal of physiology. Renal physiology Volume: - ISSN: 1522-1466 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-29 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901990 Medline TA: Am J Physiol Renal Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1Georgia Health Sciences University. |
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