Dr Ghassan Maghzal

E:
T: +61 2 9036 3212

• Biographical info
• Research
• Publications

Qualifications

MSc(Hons) (University of Canterbury, New Zealand)
PhD in Pathology (University of Otago, New Zealand)

Research interests

My research focus is primarily in the field of redox biochemistry and free radical biology and medicine. I have a particular interest in establishing methods to examine cellular oxidative stress, using analytical tools such as liquid chromatography, electrochemical detection and mass spectrometry but also protein chemistry and molecular biology. I am also interested in the post-translational modification of proteins especially modifications of the oxidative nature.

My current projects involve examining the mechanism behind the reductive activation of indoleamine 2,3-dioxygenase and also the proposed cytoprotectant activity of biliverdin reductase, the enzyme responsible for the conversion biliverdin to the pigment bilirubin.

Project: The role of superoxide in the activation of indoleamine 2,3-dioxygenase

Indoleamine 2,3-dioxygenase (IDO) is a cellular heme enzyme that catalyzes the oxidative metabolism of L Tryptophan to kynurenine. The induction of IDO and the formation of kynurenine and its metabolites have been implicated in processes such as immune regulation, neuropathology, microbial and tumor defense and more recently by our group in the regulation of vascular tone.

IDO requires to be activated via reduction of its ferric heme. For the last 30 years, the dogma has been that superoxide anion radical (O₂^-•) is responsible for this reduction. We observed that O₂^-• can also activate recombinant human IDO. However, the extent of this activation is modest, and small changes in the cellular concentration of O₂^-• barely affect IDO activity, suggesting that O₂^-• plays only a minor role. Instead, we have obtained evidence for a role of cytochrome b5 and NAPDH cytochrome P450 reductase in the reductive activation of cellular IDO. This project will examine the role of O₂^-• versus cytochrome b5 in the activation of IDO in human brain microvascular endothelial cells versus macrophages using a combination of molecular and biochemical approaches.

• Maghzal GJ, Thomas SR, Hunt NH and Stocker R. Cytochrome b5, not superoxide anion radical, is a major reductant of indoleamine 2,3-dioxygenase in human cells. J Biol Chem 2008;283:12014-12025.
• Maghzal GJ & Stocker R. Improved analysis of hydroethidine and 2-hydroxyethidium by HPLC and electrochemical detection. Free Radic Biol Med 2007;43:1095-1096
• Akerstrom B, Maghzal GJ, Winterbourn CC, Kettle AJ. The lipocalin α1-microglobulin has radical scavenging activity. J Biol Chem 2007;282:31493-31503.
• Peskin AV, Low FM, Paton LN, Maghzal GJ, Hampton MB, Winterbourn CC. The high reactivity of peroxiredoxin 2 with H2O2 is not reflected in its reaction with other oxidants and thiol reagents. J Biol Chem 2007;282:11885-11892.
• Ximenes VF, de O Silva S, Rodrigues MR, Catalani LH, Maghzal GJ, Kettle AJ and Campa A. Superoxide-dependent oxidation of melatonin by myeloperoxidase. J Biol Chem 2005;280:38160-38169.
• de Raucourt E, de Mazancourt P , Maghzal GJ, Brennan SO and Mosesson MW. Fibrinogen Saint-Germain II: Hypofibrinogenemia due to heterozygous γ N345S mutation. Thromb Haemostasis 2005;94:965-968.
• Maghzal GJ, Brennan SO and George PM. The sialic acid content of fibrinogen decreases during pregnancy and increases in response to fibrate therapy. Thrombosis Res 2005;115:293-299.
• Maghzal GJ, Brennan SO, Homer VM and George PM. The molecular mechanisms of hypofibrinogenaemia. Cell Mol Life Sci 2004;61:1427-1438.
• Maghzal GJ, Brennan SO and George PM. Fibrinogen Bβ polymorphisms do not directly contribute to an altered clot structure in humans. Thrombosis Haemostasis 2003;90:1021-1028.
• Maghzal GJ, Brennan SO, Fellowes AP, Spearing R and George PM. Familial hypofibrinogenaemia associated with heterozygous substitution of a conserved arginine residue; Bβ255 Arg–>His (Fibrinogen Merivale). Biochim Biophys Acta 2003;1645:146-151.
• Brennan SO, Maghzal GJ, Shneider BL, Gordon R, Magid MS and George PM. Novel fibrinogen γ375 Arg–>Trp mutation (Fibrinogen Aguadilla) causes hepatic endoplasmic reticulum storage and hypofibrinogenemia. Hepatology 2002;36:652-658.
• Gieseg SP, Maghzal G and Glubb D. Protection of erythrocytes by the macrophage synthesized antioxidant 7,8 dihydroneopterin. Free Radic Res 2001;34:123-136.
• Gieseg SP, Maghzal G and Glubb D. Inhibition of haemolysis by the macrophage synthesized antioxidant, 7,8-dihydroneopterin. Redox Report 2000;5:98-100.