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AKAP121 downregulation impairs protective cAMP signals, promotes mitochondrial dysfunction, and increases oxidative

Cinzia Perrino1, Antonio Feliciello, Gabriele G Schiattarella

  • 1Department of Clinical Medicine, Cardiovascular and Immunological Sciences, Federico II University, Naples 80131, Italy. perrino@unina.it

Cardiovascular Research
|June 1, 2010
PubMed
Abstract

Insights

The scaffold protein AKAP121 is crucial for heart cell survival and mitochondrial function. Its downregulation in cardiac hypertrophy leads to dysfunction, oxidative stress, and apoptosis, highlighting its role in stress response.

Area of Science:

  • Cardiovascular Biology
  • Mitochondrial Research
  • Cellular Signaling

Background:

  • AKAP121 (A-kinase anchoring protein 121) anchors cAMP-dependent protein kinase A to mitochondria.
  • Mitochondrial localization of AKAP121 is critical for cardiac function.

Purpose of the Study:

  • To determine the function and role of AKAP121 in neonatal ventricular myocytes and the heart.
  • To investigate AKAP121's involvement in mitochondrial function, reactive oxygen species (ROS) generation, and cell survival.

Main Methods:

  • Utilized competitive peptides to displace AKAP121 from mitochondria in vitro and in vivo.
  • Investigated AKAP121 levels and function in a rat model of cardiac hypertrophy induced by ascending aorta banding.

Main Results:

  • AKAP121 displacement triggered cardiomyocyte death.
  • Downregulation of AKAP121 in cardiac hypertrophy correlated with mitochondrial dysfunction, increased ROS, and apoptosis.
  • In vivo AKAP121 delocalization mimicked molecular changes seen in pressure overload.

Conclusions:

  • AKAP121 regulates the stress response in cardiomyocytes.
  • AKAP121 downregulation is implicated in the development of cardiac dysfunction.

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