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levels and HO-1 expression in
renal medullary interstitial cells
Departments of Physiology and Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226
The present study hypothesized that
superoxide (O
expression at
posttranscriptional levels in renal medullary interstitial cells
(RMICs) of rats. By Western blot analysis, it was found that incubation
of RMICs with O levels and completely
blocked the increase in HIF-1 levels induced by ubiquitin-proteasome inhibition with CBZ-LLL in the nuclear extracts from these cells. Under
normoxic conditions, a cell-permeable O levels in RMICs. Two
mechanistically different inhibitors of NAD(P)H oxidase, diphenyleneiodonium and apocynin, were also found to increase HIF-1
levels in these renal cells. Moreover, introduction of an anti-sense
oligodeoxynucleotide specific to NAD(P)H oxidase subunit,
p22phox, into RMICs markedly increased HIF-1
levels. In contrast, the OH· scavenger tetramethylthiourea had no
effect on the accumulation of HIF-1 in these renal cells. By
Northern blot analysis, scavenging or dismutation of
O-targeted gene, heme oxygenase-1. These
results indicate that increased intracellular O degradation independently of
H2O2 and OH· radicals in RMICs. NAD(P)H oxidase activity may importantly contribute to this posttranscriptional regulation of HIF-1 in these cells under physiological conditions.
reactive oxygen species; gene transcription; anoxia; renal interstitium; renal medulla
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