TY - JOUR
T1 - Citrate synthase is a novel in vivo matrix metalloproteinase-9 substrate that regulates mitochondrial function in the postmyocardial infarction left ventricle
AU - De Castro Brás, Lisandra E.
AU - Cates, Courtney A.
AU - DeLeon-Pennell, Kristine Y.
AU - Ma, Yonggang
AU - Iyer, Rugmani Padmanabhan
AU - Halade, Ganesh V.
AU - Yabluchanskiy, Andriy
AU - Fields, Gregg B.
AU - Weintraub, Susan T.
AU - Lindsey, Merry L.
N1 - Publisher Copyright:
Copyright © 2014, Mary Ann Liebert, Inc.
PY - 2014/11/10
Y1 - 2014/11/10
N2 - 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.
AB - 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.
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U2 - 10.1089/ars.2013.5411
DO - 10.1089/ars.2013.5411
M3 - Article
C2 - 24382150
AN - SCOPUS:84906049058
SN - 1523-0864
VL - 21
SP - 1974
EP - 1985
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
IS - 14
ER -