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EXPRESSION OF TYPE 2A PROTEIN PHOSPHATASES IN CARDIAC HEALTH AND DISEASE
  1. O Eleftheriadou1,
  2. MR Longman1,
  3. A Boguslavskyi2,
  4. A Ryan1,
  5. BE Wadzinski3,
  6. MJ Shattock2,
  7. AK Snabaitis1
  1. 1School of Pharmacy and Chemistry, SEC Faculty, Kingston University, Kingston-upon-Thames, Surrey, UK
  2. 2Cardiovascular Division, King's College London, The Rayne Institute, St Thomas' Hospital, London, UK
  3. 3Department of Pharmacology, Vanderbilt University, Nashville, Tennessee, USA

Abstract

Cardiac physiology and hypertrophy is regulated by the phosphorylation status of many proteins, which is regulated (in part) by activity of the type 2A serine/threonine protein phosphatase family. Phosphatase activity of this family is conferred by the homologous PP2ACα/β, PP4C and PP6C catalytic subunits. Using quantitative PCR, gene expression of type 2A phosphatases showed that PP6C mRNA (5.07) expressed as relative units (RU) was higher than PP2ACα (3.52), PP2ACβ (3.24) and PP4C (4.54) in H9c2 cardiomyocytes. However, in adult rat ventricular myocytes (ARVM), PP4C mRNA (6.42) was higher than PP2ACα (2.52), PP2ACβ (3.93) and PP6C (4.96). Using Western immunoblotting, PP2ACα/β protein expression was similar in both H9c2 cardiomyocytes and ARVM. PP6C protein expression in ARVM was significantly higher (P<0.05) when compared to H9c2 cardiomyocytes, while PP4C protein expression in ARVM was undetectable. Additionally, we showed that 28 days of transverse aortic constriction in the mouse induced a ∼61% increase in the left ventricular (LV) mass index and a significant increase (p<0.01) in the expression of PP2ACα/β protein when compared to sham-operated LV myocardium. PP4C protein expression was not detectable  in sham or hypertrophied LV myocardium, whereas PP6C protein expression was similar in both groups. This study illustrates the differences in the expression of the type 2A protein phosphatases in both H9c2 cardiomyocytes, ARVM and also highlights the importance of PP2A in cardiac pathological hypertrophy. Future work will aim to identify substrates of PP2ACα, PP2ACβ, PP4C and PP6C related to calcium regulation and hypertrophy in cardiomyocytes using small interfering RNA.

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