AMPK Methods and Protocols

Chapter 21

Studying the Role of AMPK in Cardiac Hypertrophy

and Protein Synthesis

Florence Mailleux, Christophe Beauloye, Jean-Luc Balligand,

Sandrine Horman, and Luc Bertrand

Abstract

Pathological cardiac hypertrophy, which is a compensatory mechanism established to maintain cardiac
function in response to neurohormonal or mechanical stresses, becomes maladaptive with time and
frequently leads to heart failure. AMP-activated protein kinase (AMPK) has been extensively described in
the literature to act as a break in cardiac hypertrophy development. Its anti-hypertrophic action mostly
correlates with the inhibition of several important players of cardiac hypertrophy including protein synthesis
and pro-hypertrophic gene expression pathways involving the transcription factor nuclear factor of acti-
vated T cells (NFAT) and the mitogen-activated protein kinases ERK1/2. In this chapter, we describe
methodologies designed to evaluate cardiomyocyte hypertrophy and its major molecular mechanisms in
response to AMPK activation. Two different compounds, AICAr and the biguanide phenformin, were used
to promote AMPK activation.

Key wordsAICAr, AMP-activated protein kinase, Cardiac hypertrophy, eEF2, ERK1/2, NFAT,

p70S6K, Phenformin, Protein synthesis

1 Introduction

Cardiac AMP-activated protein kinase (AMPK) has been firstly

described to act as a cellular fuel gauge which senses energetic

disequilibrium occurring under metabolic stress such as myocardial

ischemia [1]. The reduction in substrate and oxygen supply occur-

ring during such circumstances induces the increase in AMP con-

centration responsible for AMPK activation. Once activated,

AMPK protects the ischemic cardiomyocytes by activating energy

producing pathways including glycolysis and by inhibiting various

anabolic pathways such as protein synthesis [2–5]. However, it is

commonly accepted today that AMPK action extends beyond

metabolism. Indeed, AMPK can be activated, independently of

AMP, by a rise in calcium concentration, and there is an increasing

number of AMPK substrates more recently discovered and

Dietbert Neumann and Benoit Viollet (eds.),AMPK: Methods and Protocols, Methods in Molecular Biology, vol. 1732,
https://doi.org/10.1007/978-1-4939-7598-3_21,©Springer Science+Business Media, LLC 2018

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