Journal of Clinical Endocrinology & Metabolism, Vol 74, 737-742, Copyright © 1992 by Endocrine Society

ARTICLES

Methimazole and propylthiouracil inhibit the oxygen free radical- induced expression of a 72 kilodalton heat shock protein in Graves' retroocular fibroblasts

AE Heufelder, BE Wenzel and RS Bahn
Department of Internal Medicine, Mayo Clinic/Foundation, Rochester, MN 55905.

Reactive oxygen species are generated in tissues by activated mononuclear cells and macrophages. These cells infiltrate the thyroid gland in Graves' disease (GD), as well as the retroocular and pretibial space in Graves' ophthalmopathy and pretibial myxedema (PTM). Because a 72 kilodalton heat shock protein (HSP 72) is associated with autoimmune thyroid disease and is selectively expressed in fibroblasts derived from involved sites of patients with Graves' ophthalmopathy and pretibial myxedema, we studied the influence of oxygen free radicals (OFR), oxygen radical scavangers (ORS), and antithyroid drugs on HSP 72 expression in Graves' retroocular fibroblasts. Fibroblast monolayers were exposed to hydrogen peroxide (H2O2) or heat stress with simultaneous treatment, or pretreatment, with the ORS diaminobenzidine, nicotinamide, glutathione, propylthiouracil (PTU), or methimazole (MT). HSP 72 expression was determined by sodium dodecylsulfate polyacrylamide-gel electrophoresis, followed by immunoblotting with an anti-HSP 72 monoclonal antibody and densitometric quantitation of HSP 72 immunoreactivity. Baseline HSP 72 expression in Graves' retroocular fibroblasts was strongly enhanced by H2O2 and heat stress. Both pretreatment and simultaneous treatment with the ORS and any of the antithyroid agents significantly reduced the abundance of H2O2-induced (P less than 0.01), and to a lesser degree heat-induced (P less than 0.05), HSP 72 expression. These results demonstrate that, in Graves' retroocular fibroblasts, H2O2-induced HSP 72 expression is diminished both by classical ORS and by the antithyroid agents PTU and MT. In addition, heat-induced HSP 72 expression appears to be mediated in part by OFR. Stimulation of immunogenic 70 kilodalton HSPs by OFR, derived from immunocompetent cells infiltrating the affected tissues in GD, may play a role in the autoimmune process. The beneficial effect of MT and PTU on the clinical course and immune status of patients with GD may be related to their OFR-scavanging properties.

This article has been cited by other articles:

				G Sener, L Kabasakal, B M Atasoy, C Erzik, A Velioglu-Ogunc, S Cetinel, G Contuk, N Gedik, and B C Yegen Propylthiouracil-induced hypothyroidism protects ionizing radiation-induced multiple organ damage in rats. J. Endocrinol., May 1, 2006; 189(2): 257 - 269. [Abstract] [Full Text] [PDF]

				J. Nishizawa, A. Nakai, K. Matsuda, M. Komeda, T. Ban, and K. Nagata Reactive Oxygen Species Play an Important Role in the Activation of Heat Shock Factor 1 in Ischemic-Reperfused Heart Circulation, February 23, 1999; 99(7): 934 - 941. [Abstract] [Full Text] [PDF]

				Z. Liu and D. M. Stocco Heat Shock-Induced Inhibition of Acute Steroidogenesis in MA-10 Cells Is Associated with Inhibition of the Synthesis of the Steroidogenic Acute Regulatory Protein Endocrinology, July 1, 1997; 138(7): 2722 - 2728. [Abstract] [Full Text] [PDF]

				H. Kim, T.-H. Lee, E. S. Park, J. M. Suh, S. J. Park, H. K. Chung, O-Y. Kwon, Y. K. Kim, H. K. Ro, and M. Shong Role of Peroxiredoxins in Regulating Intracellular Hydrogen Peroxide and Hydrogen Peroxide-induced Apoptosis in Thyroid Cells J. Biol. Chem., June 9, 2000; 275(24): 18266 - 18270. [Abstract] [Full Text] [PDF]