Zinc Homeostasis in Platelet-Related Diseases

Abstract

Zn2+ deficiency in the human population is frequent in underdeveloped countries. Worldwide, approximatively 2 billion people consume Zn2+-deficient diets, accounting for 1–4% of deaths each year, mainly in infants with a compromised immune system. Depending on the severity of Zn2+ 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 Zn2+ status in patients with metastatic squamous cell carcinoma or with advanced non-Hodgkin lymphoma, was accompanied by cutaneous bleeding and platelet dysfunction. Forcing Zn2+ uptake in the gut using different nutritional supplementation of Zn2+ could ameliorate many of these pathological symptoms in humans. Feeding adult rodents with a low Zn2+ diet caused poor platelet aggregation and increased bleeding tendency, thereby attracting great scientific interest in investigating the role of Zn2+ in hemostasis. Storage protein metallothionein maintains or releases Zn2+ in the cytoplasm, and the dynamic change of this cytoplasmic Zn2+ pool is regulated by the redox status of the cell. An increase of labile Zn2+ pool can be toxic for the cells, and therefore cytoplasmic Zn2+ levels are tightly regulated by several Zn2+ transporters located on the cell surface and also on the intracellular membrane of Zn2+ storage organelles, such as secretory vesicles, endoplasmic reticulum or Golgi apparatus. Although Zn2+ 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 Zn2+ transport and the physiological role of Zn2+ store in megakaryocyte and platelet function remain elusive. In this review, we summarize the contribution of extracellular or intracellular Zn2+ to megakaryocyte and platelet function and discuss the consequences of dysregulated Zn2+ homeostasis in platelet-related diseases by focusing on thrombosis, ischemic stroke and storage pool diseases.

Association between Serum Zinc and Calcification Propensity (T50) in Patients with Type 2 Diabetes Mellitus and In Vitro Effect of Exogenous Zinc on T50

“…In the present study, serum zinc levels were measured according to published practical guidelines for zinc deficiency in Japan [30]. However, fibrinogen contains several binding sites for zin ions [67,68]. Because some zinc might have been removed from the blood samples during extraction of the clots, measurement of zinc in plasma obtained with tubes containing a non-chelation-based anticoagulant might be better than the method used in our study [69].…”

Zinc for the prevention and treatment of SARS-CoV-2 and other acute viral respiratory infections: a rapid review

“…Along with the positive findings from the limited systematic reviews to date, the rationale for the use of zinc in SARS-CoV-2 prevention and treatment, and possibly rehabilitation, is supported by the known mechanistic actions of zinc as an antiviral agent [40] , [42] , [43] , and a key element for a broad range of functions in the body that modulate immunity, respiratory tract inflammation, coagulation and neurological function to name a few [14] , [38] , [39] , [40] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] .…”

“…The potential role of zinc as an adjuvant therapy for SARS-CoV-2 may be broader than just antiviral and/or immunological support. Zinc also plays a complex role in haemostatic modulation acting as an effector of coagulation, anticoagulation and fibrinolysis [53] , [54] . Zinc is also essential for neurological function and normalisation of zinc intake has been shown to improve neurological recovery following stroke [14] .…”

Micronutrients, Non-Nutrients and Mediterranean Diet: A Potential Protective Role Against COVID-19 through Modulation of PAF Actions and Metabolism

“…The interrelation of PAF with zinc, copper and magnesium is not very clear. A low zinc diet reduces platelet aggregation suggesting a role of this nutrient in haemostasis [125], while zinc and copper chelate complexes have a PAF inhibitory activity mainly attributed to stereochemical interactions [126,127]. Chelating agents such as Mg 2+ , reduce the activity of PAF biosynthetic enzymes, such as Lyso-PAF-acetyltransferase [128].…”