β 2-adrenoceptors, NADPH oxidase, ROS and p38 MAPK: Another 'radical' road to heart failure?

Fabio Di Lisa, Nina Kaludercic, Nazareno Paolocci

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1009-1011
Number of pages3
JournalBritish Journal of Pharmacology
Volume162
Issue number5
DOIs
StatePublished - Mar 2011

Fingerprint

NADPH Oxidase
p38 Mitogen-Activated Protein Kinases
Adrenergic Receptors
Reactive Oxygen Species
Heart Failure
Antioxidants
NADP
Adrenergic Agents
Cysteine
Oxidoreductases
Protein Isoforms
Fibrosis
Up-Regulation
Apoptosis

Keywords

  • β /β -adrenoceptor
  • congestive heart failure
  • oxidative stress

ASJC Scopus subject areas

  • Pharmacology

Cite this

β 2-adrenoceptors, NADPH oxidase, ROS and p38 MAPK : Another 'radical' road to heart failure? / Di Lisa, Fabio; Kaludercic, Nina; Paolocci, Nazareno.

In: British Journal of Pharmacology, Vol. 162, No. 5, 03.2011, p. 1009-1011.

Research output: Contribution to journalArticle

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