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

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.

• Authors: 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
• Journal: Antioxidants & redox signaling (Antioxid Redox Signal) Vol. 21 Issue 14 Pg. 1974-85 (Nov 10 2014) ISSN: 1557-7716 [Electronic] United States
• PMID: 24382150 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Citrate (si)-Synthase
• Matrix Metalloproteinase 9

Topics

• Animals
• Citrate (si)-Synthase (metabolism)
• Heart Ventricles (metabolism, pathology)
• Humans
• Matrix Metalloproteinase 9 (genetics, metabolism)
• Mice
• Mice, Knockout
• Mitochondria (metabolism, pathology)
• Myocardial Infarction (metabolism, pathology)