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Cellular and molecular effects of chromium on the activity and expression of fibrinolytic proteins in epithelial cells.

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Call No.	QD412.C7 S58 1999
Author	Shumilla, Jennifer A.
Title	Cellular and molecular effects of chromium on the activity and expression of fibrinolytic proteins in epithelial cells.
Date	1999
Abstract	Transition metals play critical roles in biological systems as essential components of metalloproteins and metalloenzymes, as diagnostic probes and pharmaceuticals, and in some instances, as sources of toxicity. Cellular concentrations vary depending upon the metal; nevertheless, excess accumulation of any metal often leads to toxicity. Chromium has been proposed to have both beneficial and hazardous health implications depending upon its chemical nature and concentration. Chromium(III) supplementation has been shown to increase glucose metabolism in persons exhibiting impaired glucose uptake. However, exposure to chrornium(VI) causes cancer, respiratory distress, and pulmonary fibrosis. The cellular and molecular mechanisms underlying either the beneficial or deleterious effects of chromium remain unsolved. Therefore, this research defined the effects of non-cytotoxic concentrations of chromium on cellular events associated with pulmonary fibrosis and metastasis. The results of RT-PCR, ELISA, and enzyme activity studies suggest that exposure to Cr(VI) causes specific changes in expression and enzymatic activities of proteins involved in fibrinolysis, such as the urokinase-type plasminogen activator (uPA) and its cognate receptor, uPAR. These specific and selective changes rely both on reduction of Cr(VI) to Cr(III) and on the direct action of Cr(III). The cellular and molecular targets affected are at the levels of signal transduction, gene transcription, protein synthesis, and enzymatic activity. In the specific case of uPA and uPAR, the actions of Cr(VI) and Cr(III) culminate in a decreased capacity of the pulmonary cell to participate in fibrinolysis and generation of anti-angiogenic factors. These losses help explain the mechanisms through which Cr(VI) promotes pulmonary fibrosis and cancer.
Description	1 online resource (203 leaves) : illustrations
Format	application/pdf
Advisor	Barchowsky, Aaron
Subject	Chromium -- Therapeutic use. ; Fibrinolysis. ; Epithelial cells. ; Pulmonary fibrosis.
College	Dartmouth College -- Department of Chemistry.
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D)--Dartmouth College.
Copyright	In Copyright. This material is protected by copyright and/or related rights. You are free to use this material in any way that is permitted by copyright law that applies to your use. For other uses, you need to obtain permission from the rights-holder(s). http://rightsstatements.org/page/InC/1.0/
DOI	https://doi.org/10.1349/ddlp.3390

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Cellular and molecular effects of chromium on the activity and expression of fibrinolytic proteins in epithelial cells.

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