Zinc ion homeostasis in cellular physiology and experimental models of traumatic brain injury

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dc.contributor.advisor Jonathan B . Ward en_US
dc.contributor.committeeMember Wolfgang Maret en_US
dc.contributor.committeeMember Robert A . Colvin en_US
dc.contributor.committeeMember Ping Wu en_US
dc.contributor.committeeMember Karl E . Anderson en_US
dc.contributor.committeeMember Douglas S . DeWitt en_US
dc.creator Yuan Li en_US
dc.date.accessioned 2011 -12 -20T16 :04 :22Z
dc.date.accessioned 2014 -02 -19T22 :04 :57Z
dc.date.available 2010 -09 -28 en_US
dc.date.available 2011 -12 -20T16 :04 :22Z
dc.date.available 2014 -02 -19T22 :04 :57Z
dc.date.created 2009 -03 -18 en_US
dc.date.issued 2009 -03 -06 en_US
dc.identifier.other etd -03182009 -113244 en_US
dc.identifier.uri http : / /hdl .handle .net /2152 .3 /52
dc.description.abstract A major yet unsolved quest in treating traumatic brain injury (TBI ) is the understanding of the secondary cellular injury that contributes to cell death . Whether zinc ions are toxic or protective in TBI is controversial . As an essential human micronutrient , zinc is needed for the structure and function of at least 3 ,000 proteins , and thus affects almost any aspect of cellular function . Although extremely low , intracellular zinc ion concentrations , [Zn2+]i , are tightly controlled to ensure optimal physiology and to avoid toxicity . Furthermore , zinc ions are now believed to be signaling ions , especially in neuronal systems . This dissertation addresses the dynamics of [Zn2+]i and quantitatively defines its safe range in particular cell types . [Zn2+]i was measured to be pico - to nanomolar in undifferentiated and differentiated rat pheochromocytoma (PC12 ) cells and in rat glioma (C6 ) cells . When PC12 cells proliferate , [Zn2+]i undergoes precisely controlled fluctuations with two peaks within one cell cycle . These results demonstrate that the already established requirement for zinc in the cell cycle and in differentiation relates to the availability of zinc ions . In a mechanical model of cellular injury , namely rapid stretch injury (RSI ) , nitric oxide induces an increase in [Zn2+]i that subsequently may protect cells by repressing the generation of ROS . A peak at one hour was followed by decreased [Zn2+]i . In PC12 cells , [Zn2+]i dropped below its normal level , indicating that these cells were in a state of ¡°zinc ion deficiency¡± hours after RSI . In an in vivo model of neural injury , namely fluid percussion TBI of rats , changes of [Zn2+]i were indirectly demonstrated by measuring the levels and states of the zinc -binding protein , metallothionein /thionein , in the hippocampus and the cortex . These results demonstrate that [Zn2+]i as well as zinc buffering dynamically fluctuate to adapt to the requirements of cellular functions , even when [Zn2+]i is extremely low inside the cell . They suggest that toxicity occurs when [Zn2+]i falls outside the safety thresholds . Therefore , when , where , how much and in which form zinc is present determine whether chelation or supplementation is an option for treatment . These new concepts provide new leads for developing strategies to treat TBI . en_US
dc.format.medium electronic en_US
dc.language.iso eng en_US
dc.rights Copyright © is held by the author . Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works . en_US
dc.subject zinc en_US
dc.subject traumatic brain injury en_US
dc.subject oxidative stress en_US
dc.subject metallothionein en_US
dc.subject mechanical cell injury en_US
dc.subject cell cycle en_US
dc.title Zinc ion homeostasis in cellular physiology and experimental models of traumatic brain injury en_US
dc.type.genre dissertation en_US
dc.type.material text en_US
thesis.degree.name PhD en_US
thesis.degree.level Doctoral en_US
thesis.degree.grantor The University of Texas Medical Branch en_US
thesis.degree.department Preventative Medicine and Community Health en_US


Zinc ion homeostasis in cellular physiology and experimental models of traumatic brain injury. Doctoral dissertation, The University of Texas Medical Branch. Available electronically from http : / /hdl .handle .net /2152 .3 /52 .

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