TY - JOUR
T1 - β 2-adrenoceptors, NADPH oxidase, ROS and p38 MAPK
T2 - Another 'radical' road to heart failure?
AU - Di Lisa, Fabio
AU - Kaludercic, Nina
AU - Paolocci, Nazareno
PY - 2011/3
Y1 - 2011/3
N2 - Persistent activation of the cardiac β-adrenergic system may contribute to the pathogenesis of congestive heart failure. Both β 1- and β 2-adrenoceptors are known to mediate these noxious effects, yet the β 1-adrenoceptor-PKA axis has received greater attention with less information available on β 2-adrenoceptor driven pathways. In the present issue, Xu and colleagues provide new evidence, showing that β 2-adrenoceptor over-expression leads to increased reactive oxygen species (ROS) emission, mainly caused by up-regulation of reduced nicotinamide adenine dinucleotide phosphate oxidase (Nox) 2 and 4. Increase in ROS levels is accompanied by p38 mitogen-activated protein kinase activation, fibrosis, apoptosis and cardiac dysfunction. Both Nox inhibition and administration of the antioxidant N-acetyl cysteine prevent these adverse effects. Interestingly, antioxidant treatment also prevents the increase in Nox expression, suggesting that β 2-adrenoceptor stimulation triggers a vicious cycle eventually amplified by both Nox isoforms. The possible existence of a circuitry to enhance ROS signalling and detrimental consequences on myocardial remodelling are also discussed, in light of the recent description of intracellular localization of Nox4.
AB - Persistent activation of the cardiac β-adrenergic system may contribute to the pathogenesis of congestive heart failure. Both β 1- and β 2-adrenoceptors are known to mediate these noxious effects, yet the β 1-adrenoceptor-PKA axis has received greater attention with less information available on β 2-adrenoceptor driven pathways. In the present issue, Xu and colleagues provide new evidence, showing that β 2-adrenoceptor over-expression leads to increased reactive oxygen species (ROS) emission, mainly caused by up-regulation of reduced nicotinamide adenine dinucleotide phosphate oxidase (Nox) 2 and 4. Increase in ROS levels is accompanied by p38 mitogen-activated protein kinase activation, fibrosis, apoptosis and cardiac dysfunction. Both Nox inhibition and administration of the antioxidant N-acetyl cysteine prevent these adverse effects. Interestingly, antioxidant treatment also prevents the increase in Nox expression, suggesting that β 2-adrenoceptor stimulation triggers a vicious cycle eventually amplified by both Nox isoforms. The possible existence of a circuitry to enhance ROS signalling and detrimental consequences on myocardial remodelling are also discussed, in light of the recent description of intracellular localization of Nox4.
KW - congestive heart failure
KW - oxidative stress
KW - β /β -adrenoceptor
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U2 - 10.1111/j.1476-5381.2010.01130.x
DO - 10.1111/j.1476-5381.2010.01130.x
M3 - Review article
C2 - 21271996
AN - SCOPUS:79551476911
SN - 0007-1188
VL - 162
SP - 1009
EP - 1011
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 5
ER -