Zinc Homeostasis Alters Zinc Transporter Protein Expression in Vascular Endothelial and Smooth Muscle Cells

• Published in: Biological trace element research Vol. 199; no. 6; pp. 2158 - 2171
• Main Authors: Abdo, Adrian I., Tran, Hai Bac, Hodge, Sandra, Beltrame, John F., Zalewski, Peter D.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2021; Springer Nature B.V
• Subjects: Anti-inflammatory agents; Biochemistry; Biomedical and Life Sciences; Biotechnology; Circulatory system; Confocal microscopy; Coronary artery; Depletion; DNA; Endothelial cells; Fluorescence; Gene expression; Homeostasis; Inflammation; Lamellipodia; Life Sciences; Metallothionein; Metallothioneins; Microscopy; Muscles; Nucleotide sequence; Nutrition; Oncology; PCR; Polymerase chain reaction; Protein expression; Protein transport; Proteins; Pseudopodia; Pulmonary arteries; Pulmonary artery; Reproductive system; Smooth muscle; Storage proteins; Transport; Vascular system; Vasodilation; Zinc; Zinc transporter; Smooth muscle cell; Endothelial cell; Zinc transporters; Zrt- and Irt-like proteins; Metallothionein
• ISSN: 0163-4984; 1559-0720
• DOI: 10.1007/s12011-020-02328-z

Introduction Zinc is an important essential micronutrient with anti-oxidative and anti-inflammatory properties in humans. The role of zinc in signalling has been characterized in the nervous, endocrine, gastrointestinal, renal and reproductive systems. Relatively little is known regarding its role in the vascular system, but the role of zinc homeostasis in augmenting vascular health and vasorelaxation is emerging. Zinc transport proteins are integral to the protective function of zinc, but knowledge of their expression in vascular endothelial and smooth muscle cells is lacking. Methodology Human coronary artery endothelial cells and pulmonary artery smooth muscle cells were assessed for gene expression (RT-PCR) of SLC39A (ZIP), SLC30A (ZnT) and metallothionein (MT) families of Zn transporters and storage proteins. Protein expression (fluorescence confocal microscopy) was then analysed for the proteins of interest that changed mRNA expression: ZIP2, ZIP12, ZnT1, ZnT2 and MT1/2. Results Endothelial and smooth muscle cell mRNA expression of ZnT1 , ZnT2 and MT1 was significantly downregulated by low and high Zn conditions, while ZIP2 and ZIP12 expression was induced by Zn depletion with the Zn chelator, TPEN. Changes in gene expression were consistent with protein expression levels for ZIP2, ZIP12 and MT1, where ZIP2 was localized to intracellular bodies and ZIP12 to lamellipodia. Conclusion Vascular endothelial and smooth muscle cells actively regulate specific Zn transport and metallothionein gene and protein expressions to achieve Zn homeostasis.