Gomez Rodriguez 2013 Abstract IOC75

From Bioblast
Gomez Rodriguez A (2013) ß-adrenergic receptor signaling interruption with two β-blockers (atenolol or nebivolol) can modify different oxidative stress related parameters linked to longevity in mouse liver. Mitochondr Physiol Network 18.03.

Link: IOC75 Open Access

Gomez Rodriguez A, Sanchez-Roman I, Naudi A, Lopez-Torres M, Pamplona R, Barja G (2013)

Event: IOC75

Alexia Gomez Rodriguez

A new mammalian longevity model based on ß-adrenergic receptor signaling interruption at the level of adenylyl cyclase has reported decreased bone and heart aging and mean and maximum longevity increases in AC5 KO (adenylyl cyclase 5 Knocking out) mice [1]. In order to clarify if an oxidative stress decrease could be involved, we first decided to mimic this model in a pharmacological way. We have previously treated C57BL/6 mice with the β1-selective blocker atenolol in the drinking water, and this decreased the global degree of membrane fatty acid unsaturation as well as various markers of protein oxidation and lipoxidation [2]. In the present study, we have tested if that effect is extensible to other tissues, like liver, and other β1-selective blockers, like nebivolol. We have treated C57BL/6 mice with atenolol in drinking water and with nebivolol through intraperitoneal injection. Atenolol treatment decreased ROS production at the level of complex III, which correlates with a decrease in the amount of this complex. Besides, atenolol was able to decrease the level of MDAL, a specific marker of lipoxidation-dependent damage to proteins which is known to be lower in long-lived animals. On the other hand, nebivolol treatment decreased the level of oxidative damage in mitochondrial DNA (a characteristic trait of long-lived animals), and increased the ratio pERK/total ERK which indicates effective blockade of the β-adrenergic signaling pathway. These results show the specificity of β-blockers by their specific target tissues, like heart, and the lower effect in other systemic organs, like liver.

  1. Yan L, Vatner DE, O'Connor JP, Ivessa A, Ge H, Chen W, Hirotani S, Ishikawa Y, Sadoshima J, Vatner SF (2007) Type 5 adenylyl cyclase disruption increases longevity and protects against stress. Cell 130: 247–258
  2. Sanchez-Roman I, Gomez J, Naudi A, Ayala V, Portero-OtΓ­n M, Lopez-Torres M, Pamplona R, Barja G (2010) The beta-blocker atenolol lowers the longevity-related degree of fatty acid unsaturation, decreases protein oxidative damage, and increases extracellular signal-regulated kinase signaling in the heart of C57BL/6 mice. Rejuv Res 13: 683–693

β€’ Keywords: Ξ²-Blockers

Labels: MiParea: Respiration  Pathology: Aging;senescence  Stress:Oxidative stress;RONS  Organism: Mouse  Tissue;cell: Liver  Preparation: Isolated mitochondria  Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III  Regulation: Redox state, Fatty acid  Coupling state: LEAK 

Affiliations and author contributions

Supported by a BFU2011-2388 Grant to GB

A. Gomez1, I. Sanchez-Roman1, A. NaudΓ­2, M. LΓ³pez-Torres1, R. Pamplona2, G. Barja1.

(1) Department of Animal Physiology II, Faculty of Biological Sciences, Complutense University, Madrid 28040, ES

(2) Department of Experimental Medicine, Faculty of Medicine, University of Lleida-IRB, Lleida 25008, ES

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