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Role of NFkB and Bcl-2 in IGFBP-3 mediated intrinsic apoptosis
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Hanke, Jennifer. Role of NFkB and Bcl-2 in IGFBP-3 mediated intrinsic apoptosis. Retrieved from https://doi.org/doi:10.7282/T3F76GD0

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TitleRole of NFkB and Bcl-2 in IGFBP-3 mediated intrinsic apoptosis
NameHanke, Jennifer (author); Cohick, Wendie S (chair); Anthony, Tracy (internal member); Bello, Nick (internal member); Rutgers University; Graduate School - New Brunswick
Date Created2017
Other Date2017-05 (degree)
SubjectEndocrinology and Animal Biosciences, Insulin-like growth factor-binding proteins, Apoptosis
Extent1 online resource (ix, 54 p. : ill.)
DescriptionThe overall goal of this work was to investigate the mechanisms by which IGFBP-3 mediates ribotoxin-induced apoptosis in the non-transformed bovine mammary epithelial cell line MAC-T. For this work, the ribotoxins anisomycin (ANS) and deoxynivalenol (DON), which both activate the intrinsic apoptotic pathway, were investigated. Similar to previous results with ANS, DON increased mRNA and protein levels of IGFBP-3 and knockdown of IGFBP-3 with small interfering (si)RNA attenuated DON-induced apoptosis. These results confirm a role for IGFBP-3 as a key player of intrinsic apoptosis associated with the ribotoxic stress response. However, the specific mechanism by which this occurs is largely unknown. The early stages of intrinsic apoptosis are carefully controlled by members of the Bcl-2 family of proteins which is comprised of both pro- and anti-apoptotic members. The overall ratio between these pro- and anti-apoptotic proteins ultimately dictates the sensitivity or resistance of the cell to apoptotic stimuli. To investigate a role for Bcl-2 proteins, MAC-T cells transfected with IGFBP-3 or control siRNA were treated with ANS or DON and cell lysates were analyzed for changes in expression of Bcl-2 family proteins. IGFBP-3 knockdown significantly increased protein and mRNA levels of the pro-survival protein Bcl-2. Since knockdown of IGFBP-3 did not affect the levels of pro-apoptotic proteins Bax and Bak, the increase in Bcl-2 increased the ratio towards one that favors survival. Given the relationship between Bcl-2 and the NFκB pathway, IGFBP-3 knockdown cells were treated with or without the NFΚB inhibitor phenethyl caffeate (PC). Inhibition of NFκB with PC decreased Bcl-2 protein expression; however, this decrease was also observed in IGFBP-3 knockdown cells in the presence of PC. These data suggest that IGFBP-3 affects Bcl-2 expression through a mechanism that is upstream of NFκB. Interestingly, treatment with PC increased basal expression of IGFBP-3 mRNA and protein, indicating that NFκB represses IGFBP-3 expression in the basal state. In conclusion, IGFBP-3 appears to inhibit expression of Bcl-2 protein. However, while NFκB increases Bcl-2 expression and inhibits IGFBP-3 expression, the mechanisms by which these pathways are linked remain elusive.
NoteM.S.
NoteIncludes bibliographical references
Noteby Jennifer Hanke
Genretheses, ETD graduate
Persistent URLhttps://doi.org/doi:10.7282/T3F76GD0
Languageeng
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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