p53 mediates autophagy and cell death by a mechanism contingent upon Bnip3

dc.contributor.authorWang, Yan
dc.contributor.examiningcommitteeSingal, Pawan (Physiology) Czubryt, Michael (Physiology) Duhamel, Todd (Kinesiology and Recreation Management)en_US
dc.contributor.supervisorKirshenbaum, Lorrie (Physiology)en_US
dc.date.accessioned2013-07-04T15:33:09Z
dc.date.available2013-07-04T15:33:09Z
dc.date.issued2013-06en_US
dc.degree.disciplinePhysiologyen_US
dc.degree.levelMaster of Science (M.Sc.)en_US
dc.description.abstractAutophagy is a process by which cells re-cycle organelles and macromolecular proteins during cellular stress. Defects in the regulation of autophagy have been associated with various human pathologies including heart failure. In the heart tumor suppressor p53 protein is known to promote apoptotic and autophagic cell death. We found p53 over-expression increased endogenous protein level of the hypoxia-inducible Bcl-2 death gene Bnip3 which leads to loss of mitochondrial membrane potential (ΔΨm). This was accompanied by autophagic flux and cell death. Conversely, loss of function of Bnip3 in cardiac myocytes or Bnip3-/- mouse embryonic fibroblasts prevented mitochondrial targeting of p53 and autophagic cell death. These data provide the first evidence for the dual regulation of autophagic cell death of cardiac myocytes by p53 that is mutually dependent on Bnip3 activation. Hence, our findings may explain how autophagy and cell death are dually regulated during cardiac stress conditions where p53 is activated.en_US
dc.description.noteOctober 2013en_US
dc.identifier.citationWang Y, Gang H, Aviv Y, Dhingra R, Margulets V, and Kirshenbaum LA. p53 Mediates Autophagy and Cell Death by a Mechanism Contingent Upon Bnip3. Hypertension. 62:70-77; 2013.en_US
dc.identifier.urihttp://hdl.handle.net/1993/21702
dc.language.isoengen_US
dc.publisherHypertensionen_US
dc.rightsopen accessen_US
dc.subjectp53en_US
dc.subjectBnip3en_US
dc.subjectautophagyen_US
dc.subjectcell deathen_US
dc.subjectcardiac myocytesen_US
dc.titlep53 mediates autophagy and cell death by a mechanism contingent upon Bnip3en_US
dc.typemaster thesisen_US
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