RETINOID-INDUCED APOPTOSIS AND PROLIFERATION OF HEPATOCYTES ARE MEDIATED BY DISTINCT NUCLEAR RECEPTORS
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Issue Date
2009-04-07Author
Bu, Pengli
Publisher
University of Kansas
Format
193 pages
Type
Dissertation
Degree Level
Ph.D.
Discipline
Pharmacology, Toxicology & Therapeutics
Rights
This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
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Show full item recordAbstract
Retinoids, derivatives of vitamin A, are important signaling molecules regulating cellular homeostasis including differentiation, apoptosis, and proliferation. In this dissertation, we examined the versatile effects of retinoids on human liver cell lines and mouse livers by genetic and biochemical approaches. The overall finding is that retinoids can cause opposing effects in liver cells. These effects are retinoid-specific, mediated by distinct nuclear receptors, and depend on intrinsic cellular settings. The first part of this dissertation studies the mechanism underlying the differential susceptibilities of human liver cancer cells to the apoptotic effect of a synthetic retinoid, fenretinide. The findings establish a role for the nuclear receptors RARβ; and Nur77 in mediating fenretinide effect. The second part of this dissertation investigates the mechanism responsible for 13-cis retinoic acid-induced liver cell proliferation. The results demonstrate that the activation of a signaling cascade PPARβ;/PDK-1/Akt is responsible for 13-cis retinoic acid-induced proliferation of liver cells.
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- Dissertations [4701]
- Pharmacy Dissertations and Theses [118]
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