Heme oxygenase activity

Narayan S, Misra UK. 1985. Delta-aminolevulinic acid synthetase and heme oxygenase activity in lung and liver of rats given DDT and endosulfan intratracheally. Bull Environ Contam Toxicol 34 24-28. 

Jeong, G.S. et al.. Comparative effects of curcuminoids on endothelial heme oxygeanse-1 expression ortho-methoxy groups are essential to enhance heme oxygenase activity and protection, Exp. Molec. Med., 38, 393, 2006. 

Sunderman, F.W., Jr., M.C. Reid, L.M. Bibeau, and J.V. Linden. 1983. Nickel induction of microsomal heme oxygenase activity in rodents. Toxicol. Appl. Pharmacol. 68 87-95. 

Heme Oxygenase Activity in Rat Liver Depending on Action of CoCli, ANITand Tween... 

Rats are treated with 120 mg/kg ANIT and Tween-80 in the same amoimt as used for diluting ANIT. Mter approximately 40 h the rats were killed and microsomes isolated as descript above. Here you can see the results of the heme oxygenase activity measurement by using 0.2 ml hemin solution and different amoimts of microsomal solution. The highest activity is measured with 0.1 ml added microsomes and decreases 5 to 9-fold at 0.4 ml added microsomes. So 0.2 ml hemin solution is too little for an increased (more than 0.1 ml) microsomal volume. So HO is rate-limited. 

Table/Graph 2. Heme oxygenase activity dependency on volume of added microsomes dependency on volume of added microsomes.

Ryter, Stefan W. Kvam, Egil Richman, Larry et al. A chromatographic assay for heme oxygenase activity in cultured human cells application to artificial heme oxygenase overexpression. Free Radical Biol. Med. 24(6), 959-971,1998. 

Dulak, J., Jozkowicz, A., Foresti, R., Kasza, A., Frick, M., Huk, L, Green, C.J., Pachinger, O., Weidinger, F., Motterlini, R. (2002). Heme oxygenase activity modulates vascular endothelial growth factor synthesis in vascular smooth muscle cells. Antioxid. Redox Signal. 4 229 0. 

Thiram and other dithiocarbamates are metabolic poisons. The acute effects of thiram are very similar to that of carbon disulfide, supporting the notion that the common metabolite of this compound is responsible for its toxic effects. The exact mechanism of toxicity is still unclear, however it has been postulated that the intracellular action of thiram involves metabolites of carbon disulfide, causing microsome injury and cytochrome P450 disruption, leading to increased heme-oxygenase activity. The intracellular mechanism of toxicity of thiram may include inhibition of monoamine oxidase, altered vitamin Bg and tryptophan metabolism, and cellular deprivation of zinc and copper. It induces accumulation of acetaldehyde in the bloodstream following ethanol or paraldehyde treatment. Thiram inhibits the in vitro conversion of dopamine to noradrenalin in cardiac and adrenal medulla cell preparations. It depresses some hepatic microsomal demethylation reactions, microsomal cytochrome P450 content and the synthesis of phospholipids. Thiram has also been shown to have moderate inhibitory action on decarboxylases and, in fish, on muscle acetylcholinesterases. 

Heme oxygenase activity is increased in kidney and liver microsomes of NiCl2-treated rats (Maines and Kappas 1977, Sunderman et al. 1983b). 

Bissell, D. M., and Hammaker, L. E. (1976a). Cytochrome P-450 heme and the regulation of hepatic heme oxygenase activity. Arch. Biochem. Biophys. 176, 91-102. 

Another promising field is in the prevention of neonatal jaundice, which is a severe hemolytic disorder caused by excessive plasma bilimbin levels in newborn babies. It has been demonstrated experimentally that the chelate dichloro(protoporphyrinIX)-tin(IV) can inhibit the heme oxygenase activity that is responsible for the degradation of heme to bile pigment. No harmful side effects have appeared in various mammals and hence this chelate has considerable potential for clinical use against neonatal jaundice [6]. 

Acute parenteral administration of cadmium decreases hepatic microsomal cytochrome P-450 content and inhibits associated mixed-function oxidase enzyme activities (Hadley et al. 1974 Means et al. 1979 Gregus et al. 1982). Decreases in hepatic mixed function oxidase activities and cytochrome P-450 content have been demonstrated after chronic cadmium dosing for 6 months (Dudley et al. 1985). The reduction in cytochrome P-450 is due to increased heme degradation, which results from cadmium stimulation of heme oxygenase activity (Maines and Kappus 1977 Eaton et al. 1980). Such an effect would alter the capacity of an organism to adequately biotransform endogenous compounds as well as other xeno-biotics. In mitochondria, cadmium inhibits the transmembrane transport of calcium (Webb 1979) and oxidative phosphorylation (Sporn et al. 1969). 

Low-Friedrich I, Schoeppe W (1991) Effects of calcium channel blockers on stress protein synthesis in cardiac myocytes. J Cardiovasc Pharmacol 17 800-806 Maines MD (1988) Heme oxygenase function. Multiplicity, regulatory mechanisms, and clinical applications. FASEB J 2 2557-2568 Maines MD, Kappas A (1977) Metals as regulators of heme metabolism physiological and toxicological implications. Science 198 1215-1221 Maines MD, Chung A-S, Kutty RK (1982) Inhibition of testicular heme oxygenase activity by cadmium a novel cellular response. J Biochem 257 14116-14121... 

A dietary deficiency of tin has been reported to depress growth, response to sound, and feed efficiency, alter the mineral composition of several organs, and cause hair loss in rats. Additionally, tin has been shown to influence heme oxygenase activity and has been associated with thymus immune and homeostatic functions. 

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