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

Research output: Contribution to journalArticle

17 Citations (Scopus)

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

Fingerprint

Citrate (si)-Synthase
Matrix Metalloproteinase 9
Infarction
Heart Ventricles
Substrates
Transcription
Fractionation
Proteomics
Solubility
Oxidation-Reduction
Mass spectrometry
Mass Spectrometry
Proteins
Genes
Innovation
Genotype
Tissue

ASJC Scopus subject areas

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

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 T.; Lindsey, Merry L.

In: Antioxidants and Redox Signaling, Vol. 21, No. 14, 10.11.2014, p. 1974-1985.

Research output: Contribution to journalArticle

De Castro Brás, LE, Cates, CA, DeLeon-Pennell, KY, Ma, Y, Iyer, RP, Halade, GV, Yabluchanskiy, A, Fields, GB, Weintraub, ST & Lindsey, ML 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, vol. 21, no. 14, pp. 1974-1985. https://doi.org/10.1089/ars.2013.5411
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. ; Lindsey, Merry L. / Citrate synthase is a novel in vivo matrix metalloproteinase-9 substrate that regulates mitochondrial function in the postmyocardial infarction left ventricle. In: Antioxidants and Redox Signaling. 2014 ; Vol. 21, No. 14. pp. 1974-1985.
@article{4726552e600b4cbf8ddf3d82737428bc,
title = "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. Antioxid. Redox Signal. 21, 1974-1985.",
author = "{De Castro Br{\'a}s}, {Lisandra E.} and Cates, {Courtney A.} and DeLeon-Pennell, {Kristine Y.} and Yonggang Ma and Iyer, {Rugmani Padmanabhan} and Halade, {Ganesh V.} and Andriy Yabluchanskiy and Fields, {Gregg B.} and Weintraub, {Susan T.} and Lindsey, {Merry L}",
year = "2014",
month = "11",
day = "10",
doi = "10.1089/ars.2013.5411",
language = "English (US)",
volume = "21",
pages = "1974--1985",
journal = "Antioxidants and Redox Signaling",
issn = "1523-0864",
publisher = "Mary Ann Liebert Inc.",
number = "14",

}

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

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.

UR - http://www.scopus.com/inward/record.url?scp=84906049058&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84906049058&partnerID=8YFLogxK

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 -