Abstract
BackgroundExtracellular matrix (ECM) remodeling facilitates biomechanical signals in response to abnormal physiological conditions. This process is witnessed as one of the major effects of the stress imposed by catecholamines, such as epinephrine and norepinephrine (NE), on cardiac muscle cells. Matrix metalloproteinases (MMPs) are the key proteases involved in degradation of the ECM in heart.ObjectivesThe present study focuses on studying the effect of curcumin on Gelatinase B (MMP-9), an ECM remodeling regulatory enzyme, in NE-induced cardiac stress. Curcumin, a bioactive polyphenol found in the spice turmeric, has been studied for its multi-fold beneficial properties. This study focuses on investigating the role of curcumin as a cardio-protectant.MethodsH9c2 cardiomyocytes were subjected to NE and curcumin treatments to study the response in stress conditions. Effect on total collagen content was studied using Picrosirus red staining. Gelatinase B activity was assessed through Gel-Diffusion Assay and Zymographic techniques. RT-PCR, Western Blotting and Immunocytochemistry were performed to study effect on expression of gelatinase B. Further, the effect of curcumin on the localization of NF-κB, known to regulate gelatinase B, was also examined.ResultsCurcumin suppressed the increase in the total collagen content under hypertrophic stress and was found to inhibit the in-gel and in-situ gelatinolytic activity of gelatinase B. Moreover, it was found to suppress the mRNA and protein expression of gelatinase B.ConclusionsThe study provides an evidence for an overall inhibitory effect of curcumin on Gelatinase B in NE-induced hypertrophic stress in H9c2 cardiomyocytes which may contribute in the prevention of ECM remodeling.
Highlights
The catecholamines, Epinephrine and Norepinephrine (NE), have been demonstrated to pose stress conditions on the cardiac cells deteriorating their structure and function [1]
FACS data shows a decrease in the forward scatter (FSC) with curcumin treatment in presence of NEinduced stress indicating a reduction in cell size after curcumin treatment (Figure 1A)
A reduction in protein content was observed on treatment with curcumin in the presence of NE as compared to the cardiomyocytes which were treated with NE alone (Figure 1B)
Summary
The catecholamines, Epinephrine and Norepinephrine (NE), have been demonstrated to pose stress conditions on the cardiac cells deteriorating their structure and function [1]. One major effect of such stress is remodeling of the myocardial extracellular matrix (ECM) known to facilitate the biomechanical signals in response to abnormal physiological conditions [4]. Our studies reveal for the first time that curcumin suppresses the upregulated activity and expression of gelatinase B due to NE-induced stress in H9c2 cardiomyocytes. Extracellular matrix (ECM) remodeling facilitates biomechanical signals in response to abnormal physiological conditions This process is witnessed as one of the major effects of the stress imposed by catecholamines, such as epinephrine and norepinephrine (NE), on cardiac muscle cells. Results: Curcumin suppressed the increase in the total collagen content under hypertrophic stress and was found to inhibit the in-gel and in-situ gelatinolytic activity of gelatinase B. Conclusions: The study provides an evidence for an overall inhibitory effect of curcumin on Gelatinase B in NEinduced hypertrophic stress in H9c2 cardiomyocytes which may contribute in the prevention of ECM remodeling
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