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Title: Regulation of endoplasmic reticulum stress by transcription factor E2F-1 in ventricular myocytes
Authors: Mughal, Wajihah
Supervisor: Kirshenbaum, Lorrie (Physiology)
Examining Committee: Singal, Pawan (Physiology) Dhalla, NS (Physiology) Czubryt, Michael (Physiology) Duhamel, Todd (Kinesiology and Recreation Management)
Graduation Date: October 2012
Keywords: Myocytes
Endoplasmic reticulum
Issue Date: 10-Aug-2012
Abstract: E2F-1 is a transcription factor that is involved in cellular growth and regulates the transition between G1 and S phase during the cell cycle. However, the mechanisms by which E2F-1 regulates endoplasmic reticulum (ER) stress in ventricular myocytes remain poorly defined. ER stress was triggered by tunicamycin or thapsigargin; gene transcription was assessed by polymerase chain reaction and protein expression was detected by western blot. Cell viability and mitochondrial defects were assessed by fluorescent microscopy imaging. During ER stress, E2F-1 repressed signaling molecules of the unfolded protein response (UPR) and sensitized myocytes to cell death triggered by thapsigargin that was inhibited in Bnip3 null fibroblasts. Bnip3Δex3 rescued thapsigargin-induced cardiac apoptosis, blocked mitochondrial defects and rescued hypoxia/ER stress induced cardiac cell death. This study provides evidence that E2F-1 sensitizes ventricular myocytes to ER stress induced apoptosis 1) by repressing the UPR; 2) that is Bnip3 dependent; and 3) mediated by mitochondrial dysfunction.
Appears in Collection(s):FGS - Electronic Theses & Dissertations (Public)

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