Citrate Synthase is a Novel in Vivo Matrix Metalloproteinase-9 Substrate that Regulates Mitochondrial Function in the Postmyocardial Infarction Left Ventricle
Digital Object Identifier (DOI)
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.
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Citation / Publisher Attribution
Antioxidants and Redox Signaling, v. 21, issue 14, p. 1974-1985
Scholar Commons Citation
De Castro Brás, Lisandra E.; Cates, Courtney A.; DeLeon-Pennell, Kristine Y.; Ma, Yonggang; Iyer, Rugmani Padmanabhan; Halade, Ganesh V.; Yabluchanskiy, Andriy; Fields, Gregg B.; Weintraub, Susan T.; and Lindsey, Merry L., "Citrate Synthase is a Novel in Vivo Matrix Metalloproteinase-9 Substrate that Regulates Mitochondrial Function in the Postmyocardial Infarction Left Ventricle" (2014). Internal Medicine Faculty Publications. 47.