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Investigations Into the Mechanisms of Vitamin C Uptake in Rodent and Human Lens Epithelial Cells

Obrenovich, Mark E.
http://rave.ohiolink.edu/etdc/view?acc_num=case1212629235

Abstract Details

2008, Doctor of Philosophy, Case Western Reserve University, Pathology.
Vitamin C, Ascorbic Acid (ASA), was first isolated in 1928 by the Hungarian biochemist and Nobel Prize winner Albert Szent-Gyorgyi. Szent-Gyorgi described this compound, as a carbohydrate derivative Hexouric acid. ASA is a water-soluble antioxidant, somewhat unstable organic acid that is easily oxidized and destroyed when in aqueous solutions, and when dry, by oxygen or alkali and high temperature conditions. In the reduced state, ASA is an essential nutrient, cofactor and antioxidant. Now, new evidence comes from carbohydrate research, which has focused largely on nonenzymatic glycation as a type of carbonyl stress in animals, first ascribed to glucose, which implicates ascorbic acid as a contributor in the same glycation-derived post-translational modifications to protein or damage to DNA, lipids and most other biomolecules. Of particularly importance are the oxidation and degradation compounds of ASA that are implicated in pathological processes, similar to glycation but in a process now referred to as ascorbylation, because they also accumulate during aging and in age-related diseases, including diabetes, Alzheimer disease, other conformational diseases and in cataracts. Non-enzymatic ascorbylation, like glycation, is also implicated in normal aging and can form many if not the same advanced glycation endproducts (AGEs). AGEs, especially the crosslinks, have been hypothesized to be a major contributing factor in many pathological processes. Lens and collagen have been suggested to be the major tissues affected by glycation-mediated damage. However, it is the lens where inherently high levels of ascorbic acid are believed to be the major agent of carbohydrate damage as compared to rodents, which have low ocular levels of vitamin C. Unlike most other animals, humans cannot synthesize vitamin C, rendering dietary sources an obligate necessity. Regardless of whether or not vitamin C is synthesized de novo, its uptake into tissues must be largely facilitated by active transport through the sodium-dependent vitamin C transporters (SVCT1 and 2) in order to be concentrated against a gradient. The possibility of anionic channels and passive transport has not been entirely ruled out as part of the explanation for the homeostasis of ASA in tissues. Nevertheless, we have turned our attention to understanding the mechanism of ascorbate transport in ocular tissues and that body of work is described herein.
Vincent Monnier, MD (Advisor)
Robert Petersen, PhD (Advisor)
Mark Smith, PhD (Committee Chair)
Clive Hamlin, PhD (Committee Member)
Quinzhong Kong, PhD (Committee Member)
Ram Nagaraj, PhD (Committee Member)
198 p.
Pathology
Aging; lens; glycation; ascorbic acid; vitamin c; glycation; SVCT2; Epithelial Cells

Recommended Citations

Citations

  • Obrenovich, M. E. (2008). Investigations Into the Mechanisms of Vitamin C Uptake in Rodent and Human Lens Epithelial Cells [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1212629235

    APA Style (7th edition)

  • Obrenovich, Mark. Investigations Into the Mechanisms of Vitamin C Uptake in Rodent and Human Lens Epithelial Cells. 2008. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1212629235.

    MLA Style (8th edition)

  • Obrenovich, Mark. "Investigations Into the Mechanisms of Vitamin C Uptake in Rodent and Human Lens Epithelial Cells." Doctoral dissertation, Case Western Reserve University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=case1212629235

    Chicago Manual of Style (17th edition)

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This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.