Citrate Synthase Is a Novel In Vivo Matrix Metalloproteinase-9 Substrate That Regulates Mitochondrial Function in the Postmyocardial Infarction Left Ventricle
Year: 2014
Type: article
Abstract: AIM: To evaluate the role of matrix metalloproteinase (MMP)-9 deletion on citrate synthase (CS) activity postmyocardial infarction (MI). RESULTS: We fractionated left ventricle (LV) samples using a differential solubility-based approach. The insoluble protein fraction was analyzed by mass spectrometry, and we identified CS as a potential intracellular substrate of MMP-9 in the MI setting. CS protein levels increased in the insoluble fraction at day 1 post-MI in both genotypes (p<0.05) but not in the noninfarcted remote region. The CS activity decreased in the infarcted tissue of wild-type (WT) mice at day 1 post-MI (p<0.05), but this was not observed in the MMP-9 null mice, suggesting that MMP-9 deletion helps to maintain the mitochondrial activity post-MI. Additionally, inflammatory gene transcription was increased post-MI in the WT mice and attenuated in the MMP-9 null mice. MMP-9 cleaved CS in vitro, generating an ∼20 kDa fragment. INNOVATION: By applying a sample fractionation and proteomics approach, we were able to identify a novel MMP-9-related altered mitochondrial metabolic activity early post-MI. CONCLUSION: Our data suggest that MMP-9 deletion improves mitochondrial function post-MI.
Source: Antioxidants and Redox Signaling
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
Funders: U.S. Department of Veterans Affairs, American Heart Association, Office of Research and Development, National Institutes of Health, U.S. Public Health Service, University of Texas Health Science Center at San Antonio, National Heart, Lung, and Blood Institute, National Cancer Institute, National Center for Complementary and Alternative Medicine, National Center for Complementary and Integrative Health
OpenAlex ID: W1877596673