Curcumin suppresses gelatinase B mediated norepinephrine induced stress in H9c2 cardiomyocytes

PLoS One. 2013 Oct 7;8(10):e76519. doi: 10.1371/journal.pone.0076519. eCollection 2013.

Abstract

Background: 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. Matrix metalloproteinases (MMPs) are the key proteases involved in degradation of the ECM in heart.

Objectives: The 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.

Methods: H9c2 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.

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. Moreover, it was found to suppress the mRNA and protein expression of gelatinase B.

Conclusions: The 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Blotting, Western
  • Cell Line
  • Cell Survival / drug effects
  • Collagen / metabolism
  • Curcumin / pharmacology*
  • Down-Regulation / drug effects
  • Extracellular Matrix / metabolism
  • Gene Expression Regulation, Enzymologic / drug effects
  • Immunohistochemistry
  • Matrix Metalloproteinase 9 / genetics*
  • Matrix Metalloproteinase 9 / metabolism
  • Models, Genetic
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Norepinephrine / pharmacology*
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stress, Physiological / drug effects

Substances

  • Adrenergic alpha-Agonists
  • Anti-Inflammatory Agents, Non-Steroidal
  • Collagen
  • Matrix Metalloproteinase 9
  • Curcumin
  • Norepinephrine

Grants and funding

This work was supported by the research grant awarded to Dr. Vibha Rani by the Department of Biotechnology, Government of India (BT/PR3978/17/766/2011). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.