Heme oxygenase-1 (HO-1) or HSP32 is the inducible isoform of heme
oxygenase which catalyzes the NADPH, O2 and cytochrome P450 reductase
dependent oxidation of heme to carbon monoxide, iron and biliverdin
that is immediately reduced to bilirubin. These products of the
HO reaction have important physiological effects: carbon monoxide
is a potent vasodilator; biliverdin and its product bilirubin are
potent antioxidants; .free. iron increases oxidative stress and
regulates the expression of many mRNAs (e.g., DCT-1, ferritin and
transferrin receptor) by affecting the conformation of iron regulatory
protein (IRP)-1 and its binding to iron regulatory elements (IREs)
in the 5.- or 3.-UTRs of the mRNAs. To date, three heme oxygenase
isoforms HO-1, HO-2 and HO-3 have been identified. HO-1, also known
as Hsp32, a major heat shock/stress response protein, is ubiquitous
and its mRNA as well as its activity can be increased several-fold
by heme, other metalloporphyrins, transition metals and stimuli
that induce cellular stress. The 5.-untranslated region (UTR) of
HO-1 has several consensus regulatory elements which include sites
for activator protein 1 (AP-1), metal responsive element (MRE),
oncogene c-myc/max heterodimer binding site (Myc/Max), antioxidant
response element (ARE) and GC box binding (Sp1). HO-1 expression
has been shown to increase in benign postatic hyperplasia (BPH)
and malignant prostate tissue suggesting a role for this stress
protein in the pathogenesis of BPH and prostate cancer. There is
recent data which indicates the ability of peroxynitrite (ONOO-)
to modulate the expression of HO-1 and suggest that the heme oxygenase
pathway contributes to protection against the cytotoxic action
of ONOO- which is a potent oxidizing agent generated by the interaction
of nitric oxide (NO) and the superoxide anion. ONOO- rapidly decomposes
to a highly reactive hydroxyl radical and nitrogen dioxide, both
of which cause oxidative damage.
- back - complete
text - |
