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Zinc Homeostasis in Platelet-Related Diseases
Zn(2+) deficiency in the human population is frequent in underdeveloped countries. Worldwide, approximatively 2 billion people consume Zn(2+)-deficient diets, accounting for 1–4% of deaths each year, mainly in infants with a compromised immune system. Depending on the severity of Zn(2+) deficiency,...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861892/ https://www.ncbi.nlm.nih.gov/pubmed/31652790 http://dx.doi.org/10.3390/ijms20215258 |
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author | Mammadova-Bach, Elmina Braun, Attila |
author_facet | Mammadova-Bach, Elmina Braun, Attila |
author_sort | Mammadova-Bach, Elmina |
collection | PubMed |
description | Zn(2+) deficiency in the human population is frequent in underdeveloped countries. Worldwide, approximatively 2 billion people consume Zn(2+)-deficient diets, accounting for 1–4% of deaths each year, mainly in infants with a compromised immune system. Depending on the severity of Zn(2+) deficiency, clinical symptoms are associated with impaired wound healing, alopecia, diarrhea, poor growth, dysfunction of the immune and nervous system with congenital abnormalities and bleeding disorders. Poor nutritional Zn(2+) status in patients with metastatic squamous cell carcinoma or with advanced non-Hodgkin lymphoma, was accompanied by cutaneous bleeding and platelet dysfunction. Forcing Zn(2+) uptake in the gut using different nutritional supplementation of Zn(2+) could ameliorate many of these pathological symptoms in humans. Feeding adult rodents with a low Zn(2+) diet caused poor platelet aggregation and increased bleeding tendency, thereby attracting great scientific interest in investigating the role of Zn(2+) in hemostasis. Storage protein metallothionein maintains or releases Zn(2+) in the cytoplasm, and the dynamic change of this cytoplasmic Zn(2+) pool is regulated by the redox status of the cell. An increase of labile Zn(2+) pool can be toxic for the cells, and therefore cytoplasmic Zn(2+) levels are tightly regulated by several Zn(2+) transporters located on the cell surface and also on the intracellular membrane of Zn(2+) storage organelles, such as secretory vesicles, endoplasmic reticulum or Golgi apparatus. Although Zn(2+) is a critical cofactor for more than 2000 transcription factors and 300 enzymes, regulating cell differentiation, proliferation, and basic metabolic functions of the cells, the molecular mechanisms of Zn(2+) transport and the physiological role of Zn(2+) store in megakaryocyte and platelet function remain elusive. In this review, we summarize the contribution of extracellular or intracellular Zn(2+) to megakaryocyte and platelet function and discuss the consequences of dysregulated Zn(2+) homeostasis in platelet-related diseases by focusing on thrombosis, ischemic stroke and storage pool diseases. |
format | Online Article Text |
id | pubmed-6861892 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68618922019-12-05 Zinc Homeostasis in Platelet-Related Diseases Mammadova-Bach, Elmina Braun, Attila Int J Mol Sci Review Zn(2+) deficiency in the human population is frequent in underdeveloped countries. Worldwide, approximatively 2 billion people consume Zn(2+)-deficient diets, accounting for 1–4% of deaths each year, mainly in infants with a compromised immune system. Depending on the severity of Zn(2+) deficiency, clinical symptoms are associated with impaired wound healing, alopecia, diarrhea, poor growth, dysfunction of the immune and nervous system with congenital abnormalities and bleeding disorders. Poor nutritional Zn(2+) status in patients with metastatic squamous cell carcinoma or with advanced non-Hodgkin lymphoma, was accompanied by cutaneous bleeding and platelet dysfunction. Forcing Zn(2+) uptake in the gut using different nutritional supplementation of Zn(2+) could ameliorate many of these pathological symptoms in humans. Feeding adult rodents with a low Zn(2+) diet caused poor platelet aggregation and increased bleeding tendency, thereby attracting great scientific interest in investigating the role of Zn(2+) in hemostasis. Storage protein metallothionein maintains or releases Zn(2+) in the cytoplasm, and the dynamic change of this cytoplasmic Zn(2+) pool is regulated by the redox status of the cell. An increase of labile Zn(2+) pool can be toxic for the cells, and therefore cytoplasmic Zn(2+) levels are tightly regulated by several Zn(2+) transporters located on the cell surface and also on the intracellular membrane of Zn(2+) storage organelles, such as secretory vesicles, endoplasmic reticulum or Golgi apparatus. Although Zn(2+) is a critical cofactor for more than 2000 transcription factors and 300 enzymes, regulating cell differentiation, proliferation, and basic metabolic functions of the cells, the molecular mechanisms of Zn(2+) transport and the physiological role of Zn(2+) store in megakaryocyte and platelet function remain elusive. In this review, we summarize the contribution of extracellular or intracellular Zn(2+) to megakaryocyte and platelet function and discuss the consequences of dysregulated Zn(2+) homeostasis in platelet-related diseases by focusing on thrombosis, ischemic stroke and storage pool diseases. MDPI 2019-10-23 /pmc/articles/PMC6861892/ /pubmed/31652790 http://dx.doi.org/10.3390/ijms20215258 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Mammadova-Bach, Elmina Braun, Attila Zinc Homeostasis in Platelet-Related Diseases |
title | Zinc Homeostasis in Platelet-Related Diseases |
title_full | Zinc Homeostasis in Platelet-Related Diseases |
title_fullStr | Zinc Homeostasis in Platelet-Related Diseases |
title_full_unstemmed | Zinc Homeostasis in Platelet-Related Diseases |
title_short | Zinc Homeostasis in Platelet-Related Diseases |
title_sort | zinc homeostasis in platelet-related diseases |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861892/ https://www.ncbi.nlm.nih.gov/pubmed/31652790 http://dx.doi.org/10.3390/ijms20215258 |
work_keys_str_mv | AT mammadovabachelmina zinchomeostasisinplateletrelateddiseases AT braunattila zinchomeostasisinplateletrelateddiseases |