Heme oxygenase-2 (HO-2) is the constitutive 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 or 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. In contrast
to HO-1, HO-2 is highly concentrated in neurons and testes. Multiple
HO-2 transcripts which differ in size and use 3 different 5. untranslated
regions (referred to as rHO-2, rHO- 2-1 and rHO-2-2) and 2 poly(A)
signals have been identified and a functional glucocorticoid response
element (GRE) in the promoter region of rHO-2 has been characterized.
In the adult rat testis, there is developmentally regulated expression
of two transcripts for HO-2 of ~2.1kb and ~1.45kb which are not
present in the brain, kidney, thymus, heart, spleen, liver or in
prepubertal 14 day old rat testis. Both of these transcripts exclusively
use rHO-2 and they contain all of the coding region exons present
in the ~1.3kb and ~1.9kb transcripts which are common to all other
organs including the adult and prepubertal rat testis. This data
suggests that HO-2 levels in the testis are controlled by glucocorticoids
and that developmental and tissue-specific
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