Arsenic exposure in humans has been implicated in the development of a myriad of non-cancerous and cancerous diseases. A reductionist approach to understanding this unusual phenomenon would suggest that arsenic-induced perturbation of a small number of fundamental biological processes could manifest as this diverse array of disease endpoints. Endocytosis is a fundamental cellular process involved in the internalization and transport of various extracellular molecules and membranous components. BEAS-2B, a human bronchial epithelial cell line, was used to characterize the effects of chronic arsenite exposure on endocytosis. Fluorophore-labeled bovine albumin, human transferrin, and human low-density lipoprotein (LDL) were the substrates utilized to measure endocytosis in BEAS-2B cells. The uptake of albumin in unexposed BEAS-2B cells is both dose-dependent and temperature sensitive. Chronic arsenite exposure in BEAS-2B cells increased the uptake of albumin by 3.4-fold after 8 hours of uptake relative to unexposed BEAS-2B cells. Pharmacological studies utilizing endocytosis inhibitors suggested that the uptake of albumin in both unexposed and arsenite-exposed BEAS-2B cells occurs through a combination of receptor-mediated endocytosis and macropinocytosis. Chronic arsenite exposure in BEAS-2B cells also increased the endocytic uptake of transferrin by 2.9-fold at 30 minutes and LDL by 1.3-fold at 2 hours relative to unexposed BEAS-2B cells. Together, the data suggests that chronic arsenite exposure can increase the rate of endocytosis. This novel finding could add mechanistic insight to the conundrum of arsenic-associated human diseases.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/626765 |
| Date | January 2017 |
| Creators | Hunjan, Anoop Singh, Hunjan, Anoop Singh |
| Contributors | Klimecki, Walter T., Klimecki, Walter T., Schroeder, Joyce A., Yao, Guang |
| Publisher | The University of Arizona. |
| Source Sets | University of Arizona |
| Language | en_US |
| Detected Language | English |
| Type | text, Electronic Thesis |
| Rights | Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. |
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