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 language | English (US) |
|---|---|
| Pages (from-to) | 1974-1985 |
| Number of pages | 12 |
| Journal | Antioxidants and Redox Signaling |
| Volume | 21 |
| Issue number | 14 |
| DOIs | |
| State | Published - Nov 10 2014 |
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ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Molecular Biology
- Physiology
- Clinical Biochemistry
Cite this
Citrate synthase is a novel in vivo matrix metalloproteinase-9 substrate that regulates mitochondrial function in the postmyocardial infarction left ventricle. / 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 E; Lindsey, Merry L.
In: Antioxidants and Redox Signaling, Vol. 21, No. 14, 10.11.2014, p. 1974-1985.Research output: Contribution to journal › Article
}
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 E
AU - Lindsey, Merry L.
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
VL - 21
SP - 1974
EP - 1985
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
SN - 1523-0864
IS - 14
ER -