ABSTRACT
The Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Departments of Physiology‡,Pharmacology & Therapeutics†,
Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, R2H 2A6
Apoptosis or programmed cell death is a highly regulated event crucial for normal embryonic development and tissue homeostasis in adult life. Defects in the regulatory pathway that govern apoptosis have been linked to a variety of human pathologies including neurodegenerative diseases and cancer. In the context of postmitotic organs such as the heart, considerable scientifi c and clinical experience has suggested that the loss of functional ventricular myocytes by an apoptotic process contributes to the decline in cardiac pump performance in patients following myocardial injury. Recent evidence has implicated the mitochondrion as central regulator of the intrinsic death pathway. Perturbations to mitochondria resulting in permeability transition pore opening, loss of inner mitochondrial membrane integrity and release of pro-apoptotic factors are considered critical terminal events in the mitochondrial death pathway. Bcl-2 and related family members promote or prevent cell death by impinging on the extrinsic and intrinsic cell death pathways. In particular Bnip3 is an inducible gene that can trigger apoptosis, autophagy or both in cells during ischemic or hypoxic stress. Th e underlying signaling pathways
and molecular factors that govern apoptosis with specifi c attention to the molecular regulation of Bnip3 in the heart will be discussed here.
