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ANO4 (Anoctamin 4) Is a Novel Marker of Zona Glomerulosa That Regulates Stimulated Aldosterone Secretion
Microarray comparison of the transcriptomes of human adrenal zona glomerulosa (ZG) and zona fasciculata found several ZG-specific genes that negatively regulate aldosterone secretion. The third and most significantly upregulated ZG-gene (19.9-fold compared with zona fasciculata, P=6.58×10(−24)) was...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott, Williams & Wilkins
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791498/ https://www.ncbi.nlm.nih.gov/pubmed/31564164 http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13287 |
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author | Maniero, Carmela Scudieri, Paolo Haris Shaikh, Lalarukh Zhao, Wanfeng Gurnell, Mark Galietta, Luis J.V. Brown, Morris J. |
author_facet | Maniero, Carmela Scudieri, Paolo Haris Shaikh, Lalarukh Zhao, Wanfeng Gurnell, Mark Galietta, Luis J.V. Brown, Morris J. |
author_sort | Maniero, Carmela |
collection | PubMed |
description | Microarray comparison of the transcriptomes of human adrenal zona glomerulosa (ZG) and zona fasciculata found several ZG-specific genes that negatively regulate aldosterone secretion. The third and most significantly upregulated ZG-gene (19.9-fold compared with zona fasciculata, P=6.58×10(−24)) was ANO4, a putative Ca(2+)-activated chloride channel. We have investigated the role of ANO4 in human adrenal, and whether it functions like the prototype anoctamin, ANO1. We evaluated ANO4 mRNA and protein expression in human adrenal by qPCR and immunohistochemistry, compared the effects of ANO4 and ANO1 overexpression on baseline and stimulated aldosterone secretion and cell proliferation in H295R cells, and analyzed ANO4 activity as a Ca(2+)-activated chloride channel in comparison with other anoctamins by a fluorescence-based functional assay. The expression of ANO4 in ZG was confirmed by qPCR as 23.21-fold upregulated compared with zona fasciculata (n=18; P=4.93×10(−7)). Immunohistochemistry found cytoplasmic, ZG-selective expression of ANO4 (anoctamin 4) protein. ANO4 overexpression in H295R cells attenuated calcium-mediated aldosterone secretion and cell proliferation in comparison to controls. The latter effects were in a different direction to those of ANO1. The functional assay showed that, in contrast to ANO1, ANO4 expression results in low levels of calcium-dependent anion transport. In conclusion, ANO4 is one of the most highly expressed genes in ZG. It attenuates stimulated aldosterone secretion and cell proliferation. Although belonging to a family of Ca(2+)-activated chloride channels, it does not generate significant plasma membrane chloride channel activity. |
format | Online Article Text |
id | pubmed-6791498 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Lippincott, Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-67914982019-11-18 ANO4 (Anoctamin 4) Is a Novel Marker of Zona Glomerulosa That Regulates Stimulated Aldosterone Secretion Maniero, Carmela Scudieri, Paolo Haris Shaikh, Lalarukh Zhao, Wanfeng Gurnell, Mark Galietta, Luis J.V. Brown, Morris J. Hypertension Original Articles Microarray comparison of the transcriptomes of human adrenal zona glomerulosa (ZG) and zona fasciculata found several ZG-specific genes that negatively regulate aldosterone secretion. The third and most significantly upregulated ZG-gene (19.9-fold compared with zona fasciculata, P=6.58×10(−24)) was ANO4, a putative Ca(2+)-activated chloride channel. We have investigated the role of ANO4 in human adrenal, and whether it functions like the prototype anoctamin, ANO1. We evaluated ANO4 mRNA and protein expression in human adrenal by qPCR and immunohistochemistry, compared the effects of ANO4 and ANO1 overexpression on baseline and stimulated aldosterone secretion and cell proliferation in H295R cells, and analyzed ANO4 activity as a Ca(2+)-activated chloride channel in comparison with other anoctamins by a fluorescence-based functional assay. The expression of ANO4 in ZG was confirmed by qPCR as 23.21-fold upregulated compared with zona fasciculata (n=18; P=4.93×10(−7)). Immunohistochemistry found cytoplasmic, ZG-selective expression of ANO4 (anoctamin 4) protein. ANO4 overexpression in H295R cells attenuated calcium-mediated aldosterone secretion and cell proliferation in comparison to controls. The latter effects were in a different direction to those of ANO1. The functional assay showed that, in contrast to ANO1, ANO4 expression results in low levels of calcium-dependent anion transport. In conclusion, ANO4 is one of the most highly expressed genes in ZG. It attenuates stimulated aldosterone secretion and cell proliferation. Although belonging to a family of Ca(2+)-activated chloride channels, it does not generate significant plasma membrane chloride channel activity. Lippincott, Williams & Wilkins 2019-11 2019-09-30 /pmc/articles/PMC6791498/ /pubmed/31564164 http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13287 Text en © 2019 The Authors. Hypertension is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited. |
spellingShingle | Original Articles Maniero, Carmela Scudieri, Paolo Haris Shaikh, Lalarukh Zhao, Wanfeng Gurnell, Mark Galietta, Luis J.V. Brown, Morris J. ANO4 (Anoctamin 4) Is a Novel Marker of Zona Glomerulosa That Regulates Stimulated Aldosterone Secretion |
title | ANO4 (Anoctamin 4) Is a Novel Marker of Zona Glomerulosa That Regulates Stimulated Aldosterone Secretion |
title_full | ANO4 (Anoctamin 4) Is a Novel Marker of Zona Glomerulosa That Regulates Stimulated Aldosterone Secretion |
title_fullStr | ANO4 (Anoctamin 4) Is a Novel Marker of Zona Glomerulosa That Regulates Stimulated Aldosterone Secretion |
title_full_unstemmed | ANO4 (Anoctamin 4) Is a Novel Marker of Zona Glomerulosa That Regulates Stimulated Aldosterone Secretion |
title_short | ANO4 (Anoctamin 4) Is a Novel Marker of Zona Glomerulosa That Regulates Stimulated Aldosterone Secretion |
title_sort | ano4 (anoctamin 4) is a novel marker of zona glomerulosa that regulates stimulated aldosterone secretion |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791498/ https://www.ncbi.nlm.nih.gov/pubmed/31564164 http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13287 |
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