Zinc Homeostasis in Platelet-Related Diseases.

Int J Mol Sci

Walther-Straub-Institute for Pharmacology and Toxicology, Ludwig-Maximilians University Munich, German Center for Lung Research, 80336 Munich, Germany.

Published: October 2019

Zn deficiency in the human population is frequent in underdeveloped countries. Worldwide, approximatively 2 billion people consume Zn-deficient diets, accounting for 1-4% of deaths each year, mainly in infants with a compromised immune system. Depending on the severity of Zn 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 status in patients with metastatic squamous cell carcinoma or with advanced non-Hodgkin lymphoma, was accompanied by cutaneous bleeding and platelet dysfunction. Forcing Zn uptake in the gut using different nutritional supplementation of Zn could ameliorate many of these pathological symptoms in humans. Feeding adult rodents with a low Zn diet caused poor platelet aggregation and increased bleeding tendency, thereby attracting great scientific interest in investigating the role of Zn in hemostasis. Storage protein metallothionein maintains or releases Zn in the cytoplasm, and the dynamic change of this cytoplasmic Zn pool is regulated by the redox status of the cell. An increase of labile Zn pool can be toxic for the cells, and therefore cytoplasmic Zn levels are tightly regulated by several Zn transporters located on the cell surface and also on the intracellular membrane of Zn storage organelles, such as secretory vesicles, endoplasmic reticulum or Golgi apparatus. Although Zn 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 transport and the physiological role of Zn store in megakaryocyte and platelet function remain elusive. In this review, we summarize the contribution of extracellular or intracellular Zn to megakaryocyte and platelet function and discuss the consequences of dysregulated Zn homeostasis in platelet-related diseases by focusing on thrombosis, ischemic stroke and storage pool diseases.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861892PMC
http://dx.doi.org/10.3390/ijms20215258DOI Listing

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