Following
ischemia,
superoxide is produced during the reperfusion phase in various organs. In renal pathophysiology, excess of free
heme, which is released from
hemeproteins under these conditions, catalyzes the formation of further
reactive oxygen species to accelerate cellular
injuries. There is accumulating evidence suggesting that transcriptional activation of
heme oxygenase (HO)-1, the rate-limiting
enzyme in
heme degradation as well as the 32-kDa
heat shock protein, participates in the defense against oxidative tissue
injuries.
Ischemia followed by reperfusion of the rat kidney accompanies significant induction of HO-1
mRNA,
protein and
enzyme activity, which is in part mediated through a rapid and transient increase in microsomal
heme concentration. Inhibition of HO activity by
tin mesoporphyrin results in a sustained and enhanced increase in microsomal
heme content, and significantly exacerbates renal function. In contrast, SnCl2 treatment, which specifically induces HO-1
mRNA and
protein in the proximal tubular epithelial cells, prevents the
ischemia-reperfusion-mediated increase in microsomal
heme concentration, and ameliorates the ischemic renal injury. In addition to these findings, recent evidence on the role of HO-1 in the kidney pathophysiology is summarized, with a particular emphasis on its protective role in the ischemic
acute renal failure.