Dexamethasone promotes hypertrophy of H9C2 cardiomyocytes through calcineurin B pathway, independent of NFAT activation.
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.
Department of Biochemistry, University of Madras, Chennai, India. sangee22_2001@yahoo.co.in.
K N
KN
Sangeetha
Centre for Food Technology, Department of Biotechnology, Anna University, Chennai, India.
B S
BS
Lakshmi
Department of Biochemistry, University of Madras, Chennai, India.
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S
Niranjali Devaraj
D019703:Calcineurin / Q000378:metabolism*; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D006801:Humans; D032383:Myocytes, Cardiac / Q000187:drug effects*; D018994:Myosin Light Chains / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism*
D018994:Myosin Light Chains; D050778:NFATC Transcription Factors; D003907:Dexamethasone; D019703:Calcineurin
Calcineurin B; Cardiac hypertrophy; Dexamethasone; H9C2; Hypertrophic signalling