Zinc Chloride: Time-Dependent Cytotoxicity, Proliferation and Promotion of Glycoprotein Synthesis and Antioxidant Gene Expression in Human Keratinocytes

The use of ionic metals such as zinc (Zn<sup>2+</sup>) is providing promising results in regenerative medicine. In this study, human keratinocytes (HaCaT cells) were treated with different concentrations of zinc chloride (ZnCl<sub>2</sub>), ranging from 1 to 800 µg/mL, for 3,...

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Main Authors: Beatriz Salesa, Roser Sabater i Serra, Ángel Serrano-Aroca
Format: Article
Language:English
Published: MDPI AG 2021-10-01
Series:Biology
Subjects:
Online Access:https://www.mdpi.com/2079-7737/10/11/1072
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author Beatriz Salesa
Roser Sabater i Serra
Ángel Serrano-Aroca
author_facet Beatriz Salesa
Roser Sabater i Serra
Ángel Serrano-Aroca
author_sort Beatriz Salesa
collection DOAJ
description The use of ionic metals such as zinc (Zn<sup>2+</sup>) is providing promising results in regenerative medicine. In this study, human keratinocytes (HaCaT cells) were treated with different concentrations of zinc chloride (ZnCl<sub>2</sub>), ranging from 1 to 800 µg/mL, for 3, 12 and 24 h. The results showed a time–concentration dependence with three non-cytotoxic concentrations (10, 5 and 1 µg/mL) and a median effective concentration value of 13.5 µg/mL at a cell exposure to ZnCl<sub>2</sub> of 24 h. However, the zinc treatment with 5 or 1 µg/mL had no effect on cell proliferation in HaCaT cells in relation to the control sample at 72 h. The effects of the Zn<sup>2+</sup> treatment on the expression of several genes related to glycoprotein synthesis, oxidative stress, proliferation and differentiation were assessed at the two lowest non-cytotoxic concentrations after 24 h of treatment. Out of 13 analyzed genes (superoxide dismutase 1 (<i>SOD1)</i>, catalase <i>(CAT)</i>, matrix metallopeptidase 1 <i>(MMP1),</i> transforming growth factor beta 1 <i>(TGFB1)</i>, glutathione peroxidase 1 (<i>GPX1),</i> fibronectin 1 (<i>FN1)</i>, hyaluronan synthase 2 <i>(HAS2)</i>, laminin subunit beta 1 <i>(LAMB1),</i> lumican <i>(LUM)</i>, cadherin 1 (<i>CDH1)</i>, collagen type IV alpha <i>(COL4A1)</i>, fibrillin (<i>FBN)</i> and versican <i>(VCAN</i>)), Zn<sup>2+</sup> was able to upregulate <i>SOD1, CAT, TGFB1, GPX1, LUM, CDH1, FBN</i> and <i>VCAN</i>, with relative expression levels of at least 1.9-fold with respect to controls. We found that ZnCl<sub>2</sub> promoted glycoprotein synthesis and antioxidant gene expression, thus confirming its great potential in biomedicine.
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spelling doaj.art-ce077195239d4f4198cdd3b0eac948bc2023-11-22T22:26:55ZengMDPI AGBiology2079-77372021-10-011011107210.3390/biology10111072Zinc Chloride: Time-Dependent Cytotoxicity, Proliferation and Promotion of Glycoprotein Synthesis and Antioxidant Gene Expression in Human KeratinocytesBeatriz Salesa0Roser Sabater i Serra1Ángel Serrano-Aroca2Biomaterials and Bioengineering Lab, Centro de Investigación Traslacional San Alberto Magno, Universidad Católica de Valencia San Vicente Mártir, 46022 València, SpainCentre for Biomaterials and Tissue Engineering, Universitat Politècnica de València, 46022 València, SpainBiomaterials and Bioengineering Lab, Centro de Investigación Traslacional San Alberto Magno, Universidad Católica de Valencia San Vicente Mártir, 46022 València, SpainThe use of ionic metals such as zinc (Zn<sup>2+</sup>) is providing promising results in regenerative medicine. In this study, human keratinocytes (HaCaT cells) were treated with different concentrations of zinc chloride (ZnCl<sub>2</sub>), ranging from 1 to 800 µg/mL, for 3, 12 and 24 h. The results showed a time–concentration dependence with three non-cytotoxic concentrations (10, 5 and 1 µg/mL) and a median effective concentration value of 13.5 µg/mL at a cell exposure to ZnCl<sub>2</sub> of 24 h. However, the zinc treatment with 5 or 1 µg/mL had no effect on cell proliferation in HaCaT cells in relation to the control sample at 72 h. The effects of the Zn<sup>2+</sup> treatment on the expression of several genes related to glycoprotein synthesis, oxidative stress, proliferation and differentiation were assessed at the two lowest non-cytotoxic concentrations after 24 h of treatment. Out of 13 analyzed genes (superoxide dismutase 1 (<i>SOD1)</i>, catalase <i>(CAT)</i>, matrix metallopeptidase 1 <i>(MMP1),</i> transforming growth factor beta 1 <i>(TGFB1)</i>, glutathione peroxidase 1 (<i>GPX1),</i> fibronectin 1 (<i>FN1)</i>, hyaluronan synthase 2 <i>(HAS2)</i>, laminin subunit beta 1 <i>(LAMB1),</i> lumican <i>(LUM)</i>, cadherin 1 (<i>CDH1)</i>, collagen type IV alpha <i>(COL4A1)</i>, fibrillin (<i>FBN)</i> and versican <i>(VCAN</i>)), Zn<sup>2+</sup> was able to upregulate <i>SOD1, CAT, TGFB1, GPX1, LUM, CDH1, FBN</i> and <i>VCAN</i>, with relative expression levels of at least 1.9-fold with respect to controls. We found that ZnCl<sub>2</sub> promoted glycoprotein synthesis and antioxidant gene expression, thus confirming its great potential in biomedicine.https://www.mdpi.com/2079-7737/10/11/1072biometalszinc ionshuman keratinocytescytotoxicitygene expressionbiomedical applications
spellingShingle Beatriz Salesa
Roser Sabater i Serra
Ángel Serrano-Aroca
Zinc Chloride: Time-Dependent Cytotoxicity, Proliferation and Promotion of Glycoprotein Synthesis and Antioxidant Gene Expression in Human Keratinocytes
Biology
biometals
zinc ions
human keratinocytes
cytotoxicity
gene expression
biomedical applications
title Zinc Chloride: Time-Dependent Cytotoxicity, Proliferation and Promotion of Glycoprotein Synthesis and Antioxidant Gene Expression in Human Keratinocytes
title_full Zinc Chloride: Time-Dependent Cytotoxicity, Proliferation and Promotion of Glycoprotein Synthesis and Antioxidant Gene Expression in Human Keratinocytes
title_fullStr Zinc Chloride: Time-Dependent Cytotoxicity, Proliferation and Promotion of Glycoprotein Synthesis and Antioxidant Gene Expression in Human Keratinocytes
title_full_unstemmed Zinc Chloride: Time-Dependent Cytotoxicity, Proliferation and Promotion of Glycoprotein Synthesis and Antioxidant Gene Expression in Human Keratinocytes
title_short Zinc Chloride: Time-Dependent Cytotoxicity, Proliferation and Promotion of Glycoprotein Synthesis and Antioxidant Gene Expression in Human Keratinocytes
title_sort zinc chloride time dependent cytotoxicity proliferation and promotion of glycoprotein synthesis and antioxidant gene expression in human keratinocytes
topic biometals
zinc ions
human keratinocytes
cytotoxicity
gene expression
biomedical applications
url https://www.mdpi.com/2079-7737/10/11/1072
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AT rosersabateriserra zincchloridetimedependentcytotoxicityproliferationandpromotionofglycoproteinsynthesisandantioxidantgeneexpressioninhumankeratinocytes
AT angelserranoaroca zincchloridetimedependentcytotoxicityproliferationandpromotionofglycoproteinsynthesisandantioxidantgeneexpressioninhumankeratinocytes