Heme oxygenase system

Figure 32-12. Schematic representation of the microsomal heme oxygenase system. (Modified from Schmid R, McDonough AF in The Porphyrins. Dolphin D [editor]. Academic Press, 1978.)...

A number of studies have examined the anti-inflammatory aetivities of CO (Abraham et al, 1988 Mannaioni et al, 2006). An activation of the heme oxygenase system and exposure to CO in vitro (Chauveau et al, 2005 Gibbons and Farrugia, 2004 Otterbein et al, 1999, 2000 Pae et al, 2004 Sethi et al, 2002) and in vivo (Dolinay et al, 2004 Nakao et al, 2003 Neto et al, 2004 Otterbein et al, 1999) revealed anti-inflainmatory activity in animal models but not in humans (Mayr et al, 2005). CO can inhibit apoptosis of endothelial cells (Soares et al, 2002). There is some evidence that upregulation of HO-1 might be beneficial in inflammatory diseases (Willis et al, 1996). In any case, the ability of CO to inhibit platelet aggregation and inflammation has important therapeutic implications and needs to be explored. 

Maines, M. (1997). The heme oxygenase system a regulator of second messenger gases. Annu. Rev. Pharmacol. Toxicol. 37 517-54. 

Yoshinaga, T., S. Sassa, and A. Kappas (1982). A comparative study of heme degradation by NADPH-cytochrome C reductase alone and by the complete heme oxygenase system. Distinctive aspects of heme degradation by NADPH-cytochrome c reductase. J. Biol. Chem. 257, 7794-7802. 

Matsui T, M Furukawa, M Unno, T Tomita, M Ikeda-Saito (2005) Roles of distal Asp in heme oxygenase from Corynebacterium diphtheriae, HmuO. A water-driven oxygen activation system. J Biol Chem 280 2981-2989. 

Improving functionality may involve a complex biocatalytic system including more than one biocatalyst, as it is the case in BDM reactions. Additionally to the BDS for instance, another biocatalyst active for BDM [395,406], which consists of a heme oxygenase or a Cytochrome reductase could be used to widen up the functionality. 

Biological Function of Heme Oxygenase Heme Oxygenase Model Systems Heme Oxygenase The Protein... 

In cellular smdies indium exposure has been associated with a general suppression of protein synthesis and the induction of heme oxygenase, which in turn is associated with the reduction of enzyme activities dependent on cytochrome P-450. The significance of these alterations in the synthesis and maintenance of various enzyme systems in relation to a possible carcinogenic response has not been determined. ... 

Of the various HSP, heme oxygenase-1, HO-1, by generating the vasoactive molecule carbon monoxide and the potent antioxidant bilirubin, represents a novel protective system potentially active against brain oxidative injury (Rossler et al.,... 

Heme oxygenase-1 is inducible and a number of compounds have been identified which induce it so as to produce carbon monoxide, biliverdin/bilirubin and Fe2+/ferritin [12]. These include aspirin, statins, curcumin (a component of turmeric) and resveratrol (a component of red wine). The induction of heme oxygenase takes many hours so that such treatments are applicable to chronic conditions. Aspirin and statins are now prescribed for the cardiovascular system but the significance of the heme oxygenase is unproven. The compounds that are catabolised to give CO provide an alternative procedure. 

Two genetically distinct heme oxygenases (HOs) have been characterized HO-1 is an inducible form, whereas HO-2 is constitutive. HO-2 is abundant in selective tissues such as brain and the cardiovascular system. HO-1 is highly inducible in many tissues in response to a variety of stresses, including infection, exposure to xenobiotics, hypoxia, and proinflammatory cytokines. The recognition that heme oxygenase is expressed in many different tissues led to studies of the role of heme degradation apart from the pathway for formation and elimination of bilirubin derived from destruction of senescent erythrocytes. 

The widespread expression of biliverdin reductase, which parallels the widespread expression of heme oxygenase, suggests that bilirubin may play a special role in particular tissues. Studies suggested that bilirubin is an excellent lipid-soluble antioxidant. Bilirubin reacts with reactive oxygen species (ROS) that oxidize bilirubin back to biliverdin. The biliverdin then is reduced again to bilirubin. This repeated cycling results in the net use of NADPH to protect cells from ROS (Fig. 22-1). This system may be especially important in neurons. 

Nascimento CG, Branco LG (2008) Role of the spinal cord heme oxygenase-carbon monoxide-cGMP pathway in the nociceptive response of rats. Eur J Pharmacol 581 71-76 Nayebi AR, Ahmadiani A (1999) Involvement of the spinal serotonergic system in tmtilgesia produced by castration. Pharmacol Biochem Behav 64 467-471 Nayebi AR, Hassapour M, Rezazadeh H (2001) Effect of chronic and acute administration of fluoxetine and its additive effect with morphine on the behavioural response in the formtilin test in rats. J Pharm Pharmacol 53 219-225... 

Essentially, all organ systems must be evaluated. Thus laboratory tests, should include complete blood count, liver and renal functional tests, and blood, nail and urine arsenic levels. Other biomarkers of arsenic exposure include nonerythrocyte porphyrin enzyme activities and urine transforming growth factor TNF-a, accompanied by induction of heme oxygenase, mitogen-activated protein kinases, the ubiquitin-dependent proteolytic pathway, and protein kinase C in various tissues. These tests are still being investigated in laboratories and their clinical usefulness remains to be proven (Chapell et al, 2001). 

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