Biomineralization: A New Mechanism of Zinc Precipitation-induced Cell and Tissue Injury

Bibliographic Details
Main Author:	Wang, Zihui
Language:	English
Published:	Ohio University / OhioLINK 2020
Subjects:	Biomedical Research zinc mitochondria traumatic brain injury stroke
Online Access:	http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1578055809097929

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spelling	ndltd-OhioLink-oai-etd.ohiolink.edu-ohiou15780558090979292021-08-03T07:13:46Z Biomineralization: A New Mechanism of Zinc Precipitation-induced Cell and Tissue Injury Wang, Zihui Biomedical Research zinc mitochondria traumatic brain injury stroke In the human body, physiological precipitations are widely known to support and protect soft tissues. However, the pathological precipitates participate in the pathogenesis of various diseases, such as atherosclerotic plaques and kidney stones. The precipitates can be formed from a number of metal ions interacting with various anions, such as zinc and phosphate. Increasing concentrations of ions promote the precipitation. It has been recognized that pathological conditions, such as hypoxia/reperfusion in traumatic brain injury, are accompanied by both intracellular and extracellular pH change. Hypoxia causes a marked reduction of pH, whereas reperfusion returns pH by washing out hydrogen ion. Much of the evidence has suggested that hypoxia/reperfusion-induced calcium accumulation promoted calcium phosphate precipitation, which caused cell and tissue injury. To be noticed, hypoxia-induced acidification also caused zinc accumulation in cells. The increased level of zinc will promote zinc precipitation during pH recovery by reperfusion. In current work, results demonstrated that hypoxia/reperfusion caused the formation of zinc phosphate precipitates. Moreover, zinc phosphate precipitate was correlated significantly with mitochondrial injury in hypoxia/reperfusion. Furthermore, prevention of zinc-related precipitation attenuated secondary injury in brain trauma. The formation of zinc phosphate precipitate was studied in vitro and in vivo. Different concentrations of zinc were used to produce precipitates in calcium-free solutions at different pH levels. Changing pH levels of extracellular solutions and the application of hypoxia/reperfusion were used to induce the formation of zinc phosphate precipitate inside cells. The intracellular location of zinc phosphate precipitate was also presented in this work. By analyzing the elemental distribution of zinc and phosphorus, I demonstrated the appearance of zinc phosphate precipitate in mitochondria. Zinc phosphate precipitates caused dramatic changes in mitochondrial structure, resulting in mitochondrial dysfunction. Traumatic brain injury was used as a model to investigate the effect of zinc precipitate in neuron and brain tissue injuries, such as brain infarction and edema, in mice. As shown in this work, preventing zinc precipitation by zinc chelator and acidic saline reduced brain infarction and edema volumes. In summary, the collective work presented here shows a zinc precipitate-mediated toxic effect in cell and animal models. Hypoxia/reperfusion-induced pH change caused zinc precipitation, resulting in mitochondrial damage and tissue injury. Reducing the formation of zinc precipitate prevents mitochondrial injury and improves outcomes in traumatic brain injury. These findings suggested a novel potential mechanism of cell and tissue injury, providing a new therapeutic strategy. Besides, zinc has been reported to be released from activated platelets and induce platelet aggregation, promoting thrombosis. In current work, I investigated the role of zinc in thrombolysis. The results indicated that zinc inhibited thrombolysis, which might be through promoting platelet aggregation. Reducing zinc-induced platelet aggregation by zinc chelator promoted thrombolysis, providing a new therapeutic strategy in stroke. 2020-06-02 English text Ohio University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1578055809097929 http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1578055809097929 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection	NDLTD
language	English
sources	NDLTD
topic	Biomedical Research zinc mitochondria traumatic brain injury stroke
spellingShingle	Biomedical Research zinc mitochondria traumatic brain injury stroke Wang, Zihui Biomineralization: A New Mechanism of Zinc Precipitation-induced Cell and Tissue Injury
author	Wang, Zihui
author_facet	Wang, Zihui
author_sort	Wang, Zihui
title	Biomineralization: A New Mechanism of Zinc Precipitation-induced Cell and Tissue Injury
title_short	Biomineralization: A New Mechanism of Zinc Precipitation-induced Cell and Tissue Injury
title_full	Biomineralization: A New Mechanism of Zinc Precipitation-induced Cell and Tissue Injury
title_fullStr	Biomineralization: A New Mechanism of Zinc Precipitation-induced Cell and Tissue Injury
title_full_unstemmed	Biomineralization: A New Mechanism of Zinc Precipitation-induced Cell and Tissue Injury
title_sort	biomineralization: a new mechanism of zinc precipitation-induced cell and tissue injury
publisher	Ohio University / OhioLINK
publishDate	2020
url	http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1578055809097929
work_keys_str_mv	AT wangzihui biomineralizationanewmechanismofzincprecipitationinducedcellandtissueinjury
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Biomineralization: A New Mechanism of Zinc Precipitation-induced Cell and Tissue Injury

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