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 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.

Zinc Chloride for Odontogenesis of Dental Pulp Stem Cells via Metallothionein Up-regulation

“…The decreased OCN expression on 10 day was noted, which may result from variances of primary cells we used but it still regained on day 14; this was consistent with a previous study that showed that OCN was a differentiation marker (33). The expression of MT increased with increasing intracellular storage of Zn concentrations, and Zn exposure has been shown to augment MT expression in a dose-dependent fashion in various cells (34). In our study, the tendency for MT expression was also similar with this dose-dependent fashion.…”

Zinc supplementation partially prevents renal pathological changes in diabetic rats☆

“…Antioxidants administered to diabetic rats or mice significantly prevented diabetes-induced renal dysfunction [45,46]. Previous studies [8,[14][15][16] and our current study (Fig. 6D) showed that induction of renal tubular MT synthesis by Zn showed a significant protection against oxidative damage.…”

“…Zn is also an effective inducer for gene and protein expression of metallothionein (MT), a potent antioxidant [8]. We have demonstrated that Zn supplementation in diabetic mice significantly induced cardiac MT expression, along with a significant prevention of the development of diabetic cardiomyopathy [9], suggesting that induction of systemic MT synthesis by Zn supplementation may be a potential approach to preventing diabetes-induced complications in multiple organs.…”

“…Zn and Zn-induced MT in the kidney were found to provide a significant protection against renal damage caused by various oxidative stress conditions [8,[14][15][16]. Given that one of the major causes for various diabetic complications is oxidative stress [2,3] and both MT and Zn act as potent antioxidants [7,8], it is urgent to clarify whether Zn-induced renal MT can protect the kidney from diabetic damage.…”

Using of chicken antibodies for metallothionein detection in human blood serum and cadmium‐treated tumour cell lines after dot‐ and electroblotting

“…Goncalves et al utilized DIA with mouse monoclonal antibody MT 1/2 UC1MT for detection of MT in cerebrospinal fluid [80]. Alscher et al used DIA with mouse monoclonal antibody clone E9 for determination of MT in proximal tubular cell culture derived from Sus scrofa influenced by zinc [81]. Cartel used DIA for control and verification of MT purification process [82].…”