title: β-adrenergic over-stimulation and cardio-myocyte apoptosis: two receptors, one organelle, two fates?
abstract: 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.
authors.forename: Ana F
authors.initials: AF
authors.lastname: Branco
authors.forename: Ana C
authors.initials: AC
authors.lastname: Moreira
authors.forename: Teresa
authors.initials: T
authors.lastname: Cunha-Oliveira
authors.forename: Renata
authors.initials: R
authors.lastname: Couto
authors.forename: Vilma A
authors.initials: VA
authors.lastname: Sardao
authors.forename: Albert A
authors.initials: AA
authors.lastname: Rizvanov
authors.forename: Andras
authors.initials: A
authors.lastname: Palotas
authors.affiliation: Asklepios-Med, H-6722 Szeged, Kossuth Lajos sgt. 23, Hungary. palotas@asklepios-med.eu.
authors.forename: Paulo J
authors.initials: PJ
authors.lastname: Oliveira
mesh_terms: D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D002395:Catecholamines / Q000494:pharmacology*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D002395:Catecholamines; D017382:Reactive Oxygen Species; D011943:Receptors, Adrenergic, beta; D002118:Calcium