Heme-oxygenase is a ubiquitous enzyme that catalyzes the initial and 
rate-limiting steps in heme catabolism yielding equimolar amounts of 
biliverdin, iron and carbon monoxide. Biliverdin is subsequently 
converted to bilirubin and the free iron is sequestered to ferritin (1).
 These products have important physiological effects as carbon monoxide 
is a potent vasodilator; biliverdin and bilirubin are potent 
antioxidants; and the free iron increases oxidative stress and regulates
 the expression of many mRNAs (2).
	There are three isoforms of heme-oxygenase, HO-1, HO-2 and HO-3; 
however HO-1 and HO-2 are the major isoforms as they both have been 
identified in mammals (3). HO-1, also known as heat shock protein 32, is
 an inducible isoform activated by most oxidative stress inducers, 
cytokines, inflammatory agents and heat shock. HO-2 is a constitutive 
isoform which is expressed under homeostatic conditions. HO-1 is also 
considered to be a cytoprotective factor in that free heme is highly 
reactive and cytotoxic, and secondly, carbon monoxide is a mediator 
inhibiting the inflammatory process and bilirubin is a scavenger for 
reactive oxygen, both of which are the end products of heme catalyzation
 (4). It has also been shown that HO-1 deficiency may cause reduced 
stress defense, a pro-inflammatory tendency (5), susceptibility to 
atherosclerotic lesion formation (6), endothelial cell injury, and 
growth retardation (7). Up-regulation of HO-1 is therefore said to be 
one of the major defense mechanisms of oxidative stress (4).

 1. Froh M. et al. (2007) World J. Gastroentereol 13(25): 3478-86.
2. Elbirt K.K. and Bonkovsky H.L. (1999) Proc Assoc Am Physicians 111(5): 348-47.
3. Maines M.D., Trakshel G.M., and Kutty R.K. (1986) J Biol Chem 261: 411–419.
4. Brydun A., et al. (2007) Hypertens Res 30(4): 341-8.
5. Poss K.D. and Tonegawa S. (1997). Proc Natl Acad Sci U S A. 94: 10925–10930.
6. Yet S.F., et al. (2003) FASEB J. 17: 1759–1761.
7. Yachie A., et al. (1999) J Clin Invest. 103: 129–135.