Citrate synthase is a novel in vivo matrix metalloproteinase-9 substrate that regulates mitochondrial function in the postmyocardial infarction left ventricle

Lisandra E. De Castro Brás, Courtney A. Cates, Kristine Y. DeLeon-Pennell, Yonggang Ma, Rugmani Padmanabhan Iyer, Ganesh V. Halade, Andriy Yabluchanskiy, Gregg B. Fields, Susan T. Weintraub, Merry L. Lindsey

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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. Antioxid. Redox Signal. 21, 1974-1985.

Original languageEnglish (US)
Pages (from-to)1974-1985
Number of pages12
JournalAntioxidants and Redox Signaling
Volume21
Issue number14
DOIs
StatePublished - Nov 10 2014

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ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

De Castro Brás, L. E., Cates, C. A., DeLeon-Pennell, K. Y., Ma, Y., Iyer, R. P., Halade, G. V., Yabluchanskiy, A., Fields, G. B., Weintraub, S. T., & Lindsey, M. L. (2014). Citrate synthase is a novel in vivo matrix metalloproteinase-9 substrate that regulates mitochondrial function in the postmyocardial infarction left ventricle. Antioxidants and Redox Signaling, 21(14), 1974-1985. https://doi.org/10.1089/ars.2013.5411