Induction of Metallothionein in Proximal Tubular Cells by Zinc and Its Potential as an Endogenous Antioxidant

Abstract

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 µ M 0.65 ± 0.26; Zn 35 µ M 1.25 ± 0.43 (p < 0.05), Zn 52 µ M 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.