Rowett Research
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 Vascular Health Programme - Lipid & Redox. Regulation Group

 Zinc Metallothionein and gene expression - Professor John Beattie

Areas of Research

• Zinc Deficiency and Heart Disease

•Cell zinc metabolism and metallothionein

• Mechanisms of Action

Zinc deficiency affects one third of the World’s population and is recognised by the WHO as a critical global nutritional deficiency. Zinc is required for the proper function of over 2500 proteins and deficiencies give rise to impaired growth, development and immunity. Even in developed countries, marginal zinc deficiency is likely to be prevalent and may have important consequences for the pathogenesis of heart disease. Our recent proteomic analysis of aorta from zinc deficient rats reveals a deficiency-related decrease in protein kinase Cα (PKCα) levels coincidental with the targeting of pathways relating to vascular smooth muscle (VSM) differentiation, fatty acid oxidation and carbohydrate metabolism.  Particular targets identified include the VSM-specific protein sm22α (transgelin 1), whose genetic ablation in apoE-null mice accelerates atherogenesis.  We are using mouse models of heart disease to better understand how marginal zinc deficiency, equivalent to that experienced by sections of the Scottish population, affect the initiation and pathogenesis of vascular disease and to define optimal dietary zinc intakes for maintaining vascular health.

Specifically, I aim to:

1. Demonstrate whether marginal zinc deficiency influences the pathogenesis of atherosclerosis using appropriate mouse models.

2. Understand the mechanisms by which zinc protects the vascular system and maintains vascular health.

3. Evaluate the role of zinc and the zinc-binding protein metallothionein in protecting the vascular system from oxidative stress.

Latest Publications

Hodkinson, C.F., Simpson, E.A.A., Beattie, J.H., O’Connor, J.M., Campbell, D.J., Strain, J.J., Wallace, J.M.W. Preliminary evidence of immune function modulation by thyroid hormones in healthy men and women aged 55-70 years. Journal of Endocrinology, 202 (1) November 2009 pp. 55-63.

Beattie, J.H., Duthie, S.J., Kwun, I-S., Ha, T-Y., Gordon, M.J. Rapid quantification of aortic lesions in ApoE (-/-) mice. Journal of Vascular Research, 46 (4) pp. 347-352.

Beattie J.H., Gordon M-J., Rucklidge G.J., Reid M.D., Duncan G.J., Horgan G.W., Cho Y.E. and Kwun I.S. (2008). Aorta protein networks in marginal and acute zinc deficiency. Proteomics , 8 : 2126-2135.

Beattie J.H. and Kwun I.S. (2004). Is zinc deficiency a risk factor for atherosclerosis? British Journal of Nutrition , 91 :177-181

Beattie J.H., Owen H.L.H., Wallace S.M., Arthur J.R., Kwun I.S., Hawksworth G.M. and Wallace H.M. (2005). Metallothionein overexpression and resistance to toxic stress. Toxicology Letters , 157 :69-78 .

Beattie J.H., Gordon M-J., Reid M.D., Rucklidge G.J., Kwon C.S. and Kwun I.S. (2006). Hepatic responses to dietary stress in zinc and metallothionein-deficient mice. Experimental Biology and Medicine , 231 : 1542-1547.

Kwon C.S., Kountouri A., Mayer C., Gordon M-J., Kwun I.S. and Beattie J.H. (2007). Mononuclear cell metallothionein mRNA levels in human subjects with poor zinc nutrition. British Journal of Nutrition , 97 : 247-254 .

Carlson D., Beattie J.H. and Poulsen H.D. (2007). Measurement of alkaline phosphatase and metallothionein mRNA in the assessment of zinc status of weaned piglets given high dietary zinc and/or copper . Journal of Animal Science and Animal Nutrition , 91 : 19-28 .

Kwun I.S., Cho Y.E., Lomeda R-A.R., Kwon, S.T., Kim Y.H. and Beattie J.H. (2007). Marginal zinc deficiency in rats decreases leptin expression independently of food intake and corticotrophin-releasing hormone in relation to food intake. British Journal of Nutrition , 98 : 485-489.

Contact details for Professor John Beattie

Email: J.Beattie@rowett.ac.uk

Telephone:+44 (0)1224 716631