Induction of Metallothionein in Proximal Tubular Cells by Zinc and Its Potential as an Endogenous AntioxidantAlscher D.M.a · Braun N.a · Biegger D.a, c · Stuelten C.d · Gawronski K.c · Mürdter T.E.c · Kuhlmann U.a · Fritz P.b
aDivision of General Internal Medicine and Nephrology, Department of Internal Medicine; bDivision of Pathology, Department of Diagnostic Medicine, Robert Bosch Krankenhaus, Stuttgart, and cMargarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany; dLaboratory of Cell Regulation and Carcinogenesis NCI, NIH, Bethesda, Md., USA
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Background: This study was undertaken to gain further insights into the expression of metallothionein (MT) in kidney, to define the necessary dosage of a metal (zinc) to achieve induction of MT and to evaluate the antioxidative potential of MT in comparison to other more common antioxidative therapeutics, like N-acetyl-L-cysteine (NAC), and endogenous molecules, like glutathione. Methods: MT was measured in renal specimens from cadaver kidneys from patients with chronic diseases (n = 76) and controls (n = 21) by immunohistochemistry. In addition, induction experiments were performed in cell cultures of proximal tubular cells (LCC-PK1) and MT measured on the RNA and protein level (immunohistochemistry, Western and dot blotting). Antioxidative potential of MT was compared to NAC and glutathione. Results: MT was restricted to tubular cells with no differences between controls and patients. Zn caused a dose-dependent increase of MT on the RNA as well as on the protein level (RNA (ratio MT/histone 3.3): control 0.34 ± 0.12; Zn 17 µM 0.65 ± 0.26; Zn 35 µM 1.25 ± 0.43 (p < 0.05), Zn 52 µM 1.35 ± 0.46 (p < 0.05), and protein: 5.8-fold increase from 47 ± 13 mg/g total protein (n = 6) to 272 ± 140 mg/g total protein (n = 6)). The antioxidative effect of MT was equal to NAC and glutathione. Conclusions: Induction of renal MT by zinc is easily achievable and might be an interesting therapeutic and preventive tool against oxidative stress.
© 2005 S. Karger AG, Basel
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