Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.14.99.3 (heme oxygenase)
 4,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apoptosis has been shown to contribute to the development of acute and chronic renal failure. The antiapoptotic action of the heme oxygenase (HO) system may represent an important protective mechanism in kidney pathology. We examined whether the lack of HO-1 would influence apoptosis in clipped kidneys of two-kidney, one-clip (2K1C) rats. Five-day-old Sprague-Dawley rats were injected in the left ventricle with approximately 5 x 10(9) colony-forming units/ml of retrovirus containing rat HO-1 antisense (LSN-RHO-1-AS) or control retrovirus (LXSN). After 3 mo, a 0.25-mm U-shaped silver clip was placed around the left renal artery. Animals were killed 3 wk later. Clipping the renal artery in LSN-RHO-1-AS rats did not result in increased HO-1 expression. In contrast to LXSN animals, 2K1C LSN-RHO-1-AS rats showed increased expression of cyclooxygenase 2 (COX-2) and higher 3-nitrotyrosine (3-NT) content as well as increased expression of the proapoptotic protein Apaf-1 and caspase-3 activity. Clipping the renal artery in LXSN rats resulted in increased expression of the antiapoptotic proteins Bcl-2 and Bcl-xl, while clipping the renal artery in LSN-RHO-1-AS rats did not change Bcl-2 levels and decreased the levels of Bcl-xl. Treatment of LSN-RHO-1-AS rats with cobalt protoporphyrin resulted in induction of renal HO-1, which was accompanied by decreases in blood pressure, COX-2, 3-NT, and caspase-3 activity, and increased expression of anti-apoptotic molecules (Bcl-2, Bcl-xl, Akt and p-Akt) in the clipped kidneys. These findings underscore the prominent role of HO-1 in counteracting apoptosis in this 2K1C renovascular hypertension model.
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PMID:Genetic suppression of HO-1 exacerbates renal damage: reversed by an increase in the antiapoptotic signaling pathway. 1694 May 61

Hypoxia of the kidney in diabetes could predispose it to develop acute and chronic renal failure. To examine the relationship between renal hypoxia and renal failure, we measured hypoxia (as a pimonidazole adducts), hypoxia-inducible factors (HIFs), and a hypoxia target gene heme oxygenase-1. The studies were performed in rats with streptozotocin (STZ)-induced diabetes, Cohen diabetes sensitive rats, and during short-term artificial hyperglycemia in rats induced by intravenous glucose and octreotide. STZ-treated rats received insulin, the superoxide dismutase mimetic tempol, or contrast medium. Radiocontrast media causes hypoxia and HIF induction. Hypoxia, HIFs, and heme oxygenase were undetectable in controls, but transiently activated in STZ-treated and the Cohen diabetes sensitive rats. Different patterns of HIFs and pimonidazole were observed between the three models. Insulin abolished pimonidazole and HIF induction, whereas tempol lead to increased HIFs and heme oxygenase induction at similar levels of pimonidazole. When compared with control rats, STZ-treated rats exhibited more intense and protracted renal pimonidazole, with augmented hypoxia inducible factor production and reduced GFR following contrast media. Our data suggest that both regional hypoxia and hypoxia adaptation transiently occur in early stages of experimental diabetes, largely dependent on hyperglycemia or after contrast media. Tempol may augment the HIF response in diabetes.
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PMID:Adaptation to hypoxia in the diabetic rat kidney. 1791 54

Renal ischemia is the most common cause of acute kidney injury (AKI) still associated with high mortality rates of about 50% in the intensive care unit. Postischemic AKI is characterized by decreased glomerular filtration rate and high renal vascular resistance with endothelial activation and dysfunction, a process of critical importance that is followed by a reduction in microvascular blood flow mainly affecting the renal outer medulla. The pathophysiology of postischemic AKI remains incompletely understood, although it seems to be a phenomenon of altered renal hemodynamics, linked critically to the production of high amounts of nitric oxide and free radicals. On the other hand, and depending on the severity of renal ischemia, tubular epithelial cells undergo a varying degree of necrosis or apoptosis with tubular obstruction followed by both, anatomical and functional recovery. The way in which vascular and tubular epithelium recover determines the final status of the renal function, ranging from full recovery to chronic renal failure and ultimately to end-stage renal disease. In this review we will revise the mechanisms responsible for these pathophysiologic alterations, including the role of heme oxygenase system and sex differences in the susceptibility to ischemic acute renal failure, and we will also review the pre- and postconditioning phenomena, in which brief episodes of ischemia before (pre-conditioning) or after (post-conditioning) the prolonged ischemia have a protective effect on AKI after reperfusion. Interestingly, these protective responses can be elicited by ischemizing distant tissues (remote conditioning). A better understanding of these mechanisms may help to improve the clinical outcome of those patients.
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PMID:Reactive oxygen and nitrogen species in the renal ischemia/reperfusion injury. 2309 23