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Molecular and Cellular Biochemistry

, Volume 411, Issue 1–2, pp 241–252 | Cite as

Dexamethasone promotes hypertrophy of H9C2 cardiomyocytes through calcineurin B pathway, independent of NFAT activation

  • K. N. Sangeetha
  • B. S. Lakshmi
  • S. Niranjali Devaraj
Article

Abstract

Metabolic syndrome-induced cardiac hypertrophy is a global concern leading to an increase in the morbidity and mortality of patients, with the signalling mechanism associated with them still unclear. The present study attempts to understand the metabolic syndrome-associated cardiac hypertrophy through an in vitro model using external stimuli well known for inducing metabolic disorders, i.e. dexamethasone (DEX), a synthetic glucocorticoid. DEX (0.1 and 1 μM) promoted cardiac hypertrophy in H9C2 cells at 4 days of treatment as evidenced through increased cell size and protein content. A significant induction in foetal gene reprogramming was observed, confirming the establishment of hypertrophy. Moreover, the hypertrophic response at 4 days was perceived to be physiological at 0.1 μM and pathological at 1 μM based on α-MHC and IGF1R expression, but complete inhibition in the PKB/AKT expression confirmed it to be pathological hypertrophy at both the concentrations (0.1 and 1 μM). The present study reports for the first time the mechanistic insights into DEX-mediated hypertrophy. It is hypothesized to be orchestrated through the activation of AT1R that is involved in the alteration of the cardiac isoform of SERCA2 expression perturbing the calcium homeostasis. This leads to the activation of calcineurin B, independent of NFAT involvement, which in coordination with ROS induces the activation of JNK of the MAPK signalling.

Keywords

Calcineurin B Cardiac hypertrophy Dexamethasone H9C2 Hypertrophic signalling 

Notes

Acknowledgments

This work was supported by UGC-Dr D S Kothari Postdoctoral fellowship awarded to Dr Sangeetha KN, by the University Grants Commission, Government of India [Award letter No. F. 13-673/2012(BSR)].

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • K. N. Sangeetha
    • 1
  • B. S. Lakshmi
    • 2
  • S. Niranjali Devaraj
    • 1
  1. 1.Department of BiochemistryUniversity of MadrasChennaiIndia
  2. 2.Centre for Food Technology, Department of BiotechnologyAnna UniversityChennaiIndia

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