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

Puromycin aminonucleoside (PAN)-induced glomerular injury in rats mimics minimal-change nephrotic syndrome (NS) in humans. We have demonstrated an important role of cytochrome P450 (CYP) as a significant source of catalytic iron in this model of NS. The current study was designed to identify CYP isozyme(s) present in the rat glomerular epithelial cells (GEC) and to explore the role of the specific CYP isozyme in PAN-induced cytotoxicity. CYP2B1 was identified in GEC by immunocytochemistry and Western blot. Treatment of GEC with PAN resulted in a marked generation of hydrogen peroxide (H(2)O(2)) and reduction of CYP2B1 content associated with significant increase in catalytic iron and hydroxyl radical formation. Preincubating GEC with CYP2B1 inhibitors (piperine and cimetidine) and H(2)O(2) scavenger (pyruvate) significantly reduced H(2)O(2 )generation, preserved CYP2B1 content, prevented the increase in catalytic iron and hydroxyl radical formation including PAN-induced cytotoxicity. We also observed the induction of heme oxygenase (HO-1) in PAN-treated GEC, and this up-regulation was reduced by pretreatment of the CYP inhibitors and pyruvate. Our data thus indicate an important role of CYP2B1 in PAN-induced cytotoxicity by serving as a site of reactive oxygen metabolite generation and a significant source of catalytic iron.
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PMID:Role of cytochrome P450 2B1 in puromycin aminonucleoside-induced cytotoxicity to glomerular epithelial cells. 1280 84