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Glucocorticoid Induction of Autophagy in Lymphocytes, Mediated by Dig2 and Inhibition of mTOR Signaling

Swerdlow, Sarah Jean
http://rave.ohiolink.edu/etdc/view?acc_num=case1252078241

Abstract Details

2010, Doctor of Philosophy, Case Western Reserve University, Pathology.
Glucocorticosteroids are important inducers of apoptosis in lymphocytes, although the mechanisms responsible for glucocorticoid-induced apoptosis are still being elucidated.We have discovered that glucocorticoid treatment of lymphocytes also induces autophagy, a highly conserved process that is necessary for cell survival under times of metabolic stress. Dexamethasone, a synthetic glucocorticoid, was used to treat immature double positive lymphocytes expressing either low or high levels of the anti-apoptotic protein, Bcl-2. Importantly, Bcl-2 inhibits glucocorticoid-induced apoptosis but not glucocorticoid-induced autophagy. We demonstrate dexamethasone-mediated induction of autophagy by multiple methods including Western blot analysis of the autophagy specific protein LC3 and by visualization of the autophagic process using electron microscopy and immunofluorescence of GFP-LC3. Furthermore, we discovered that the autophagic response is mediated in part by the dexamethasone-induced gene 2 (Dig2). Utilizing lentiviral shRNA and siRNA smartpools to knockdown Dig2, we observed a reduction of autophagy following glucocorticoid treatment at 4 hr by 12 immunofluorescence of GFP-LC3, thereby establishing the importance of Dig2 in this process. Finally, the mTOR signaling pathway was shown to be involved in dexamethasone-induced autophagy.
Clark Distelhorst (Advisor)
David Kaplan (Committee Chair)
Shigemi Matsuyama (Committee Member)
Edward Stavnezer (Committee Member)
Laxminarayana Devireddy (Committee Member)
Clive Hamlin (Committee Member)
136 p.
Biomedical Research
Autophagy; Dexamethasone; Lymphocytes; Dig2/REDD1

Recommended Citations

Citations

  • Swerdlow, S. J. (2010). Glucocorticoid Induction of Autophagy in Lymphocytes, Mediated by Dig2 and Inhibition of mTOR Signaling [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1252078241

    APA Style (7th edition)

  • Swerdlow, Sarah. Glucocorticoid Induction of Autophagy in Lymphocytes, Mediated by Dig2 and Inhibition of mTOR Signaling. 2010. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1252078241.

    MLA Style (8th edition)

  • Swerdlow, Sarah. "Glucocorticoid Induction of Autophagy in Lymphocytes, Mediated by Dig2 and Inhibition of mTOR Signaling." Doctoral dissertation, Case Western Reserve University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1252078241

    Chicago Manual of Style (17th edition)

case1252078241
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© 2009, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.