Abstract
BackgroundRecent findings suggest that adult terminally differentiated cardiomyocytes adapt to stress by cellular de- and redifferentiation. In the present study we tested the hypothesis that swiprosin-1 is a key player in this process. Furthermore, the relationship between swiprosin-1 and β-adrenoceptor coupling was analyzed.MethodsIn order to study the function of swiprosin-1 in adult rat ventricular cardiomyocytes (ARVC) they were isolated and cultured in a medium containing 20% fetal calf serum (FCS). Changes in cell morphology of ARVC during cultivation were quantified by light and confocal laser scan microscopy. Small interfering RNA (siRNA) was used to reduce the expression of swiprosin-1. The impact of calcium on swiprosin-1 dependent processes was investigated with Bapta-AM. Immunoblot techniques and qRT-PCR were performed to measure mRNA and protein expression.ResultsIn culture, ARVC first lost their contractile elements, which was followed by a formation of pseudopodia-like structures (spreading). Swiprosin-1 was detected in ARVC at all time points. However, swiprosin-1 expression was increased when ARVC started to spread. Reduction of swiprosin-1 expression with siRNA delayed ARVC spreading. Similarly, Bapta-AM attenuated swiprosin-1 expression and spreading of ARVC. Furthermore, swiprosin-1 expression correlated with the expression of G protein-coupled receptor kinase 2 (GRK2). Moreover, silencing of swiprosin-1 was associated with a down regulation of GRK2 and caused a sensitization of β-adrenergic receptors.ConclusionSwiprosin-1 is required for ARVC to adapt to culture conditions. Additionally, it seems to be involved in the desensitization of β-adrenergic receptors. Assuming that ARVC adapt to cardiac stress in a similar way, swiprosin-1 may play a key role in cardiac remodeling.
Highlights
Neonatal cardiomyocytes have the ability to perform mitosis, this capability vanishes within the first week post-partum
In order to study the function of swiprosin-1 in adult rat ventricular cardiomyocytes (ARVC) they were isolated and cultured in a medium containing 20% fetal calf serum (FCS)
Adult rat ventricular cardiomyocytes (ARVC) first lost their contractile elements, which was followed by a formation of pseudopodia-like structures
Summary
Neonatal cardiomyocytes have the ability to perform mitosis, this capability vanishes within the first week post-partum. Adult rat ventricular cardiomyocytes (ARVC) in culture perform severe structural changes including sarcomere disassembly and reformation [7]. This is accompanied by a reexpression of fetal-type genes like β-myosin heavy chain (β-MHC) and α-smooth muscle actin (α-sm-actin) [8,9]. In culture ARVC form new sarcomeres alongside actin-driven stress fibers. This is preceded by the formation of pseudopodia-like structures, a process known as cell spreading. We hypothesize that swiprosin-1 is required for the formation of pseudopodia-like structures (spreading) in ARVC. Recent findings suggest that adult terminally differentiated cardiomyocytes adapt to stress by cellular de- and redifferentiation. The relationship between swiprosin-1 and β-adrenoceptor coupling was analyzed
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