β-adrenergic over-stimulation and cardio-myocyte apoptosis: two receptors, one organelle, two fates?

• Autor(a) principal: Branco, Ana F.
• Data de Publicação: 2014
• Outros Autores: Moreira, Ana C., Cunha-Oliveira, Teresa, Couto, Renata, Sardão, Vilma A., Rizvanov, Albert A., Palotas, Andras, Oliveira, Paulo J.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10316/44868
• topic: Animals; Calcium; Catecholamines; Humans; Mitochondria; Myocytes, Cardiac; Reactive Oxygen Species; Receptors, Adrenergic, beta; Signal Transduction; Apoptosis

Neuro-hormonal regulation of cardiac function via cathecol-amines results in increased heart rate and contractility. A persistent adrenergic tone, however, is an insult to the heart, affecting its regular homeostasis, altering morphology and gene expression patterns, as well as inducing apoptosis of cardio-myocytes. At the same time as being the main oxygen consumers, mitochondria are also key to the energy production required for the heart to maintain its vital functions and to integrate a series of signaling pathways that define the life and death of the cell. As α-adrenergic receptors (α-AR) orchestrate multiple biochemical events that can either trigger or inhibit cell death, mitochondria can act as a referee in the entire process. In fact, α-AR subtypes α1 and α2 activate various down-stream pathways which differently modulate intracellular calcium levels and production of mitochondrial reactive oxygen species (ROS). The delicate balance between an adaptive (cardio-protective) response resulting in increased contractility and activation of survival pathways, vs. cell death caused by calcium and ROS-induced mitochondrial disruption, along with evidence of their clinical and potential therapeutic translations, are reviewed in this communication.