c-Myc alters substrate utilization and O-GlcNAc protein posttranslational modifications without altering cardiac function during early aortic constriction
Abstract
Pressure overload cardiac hypertrophy alters substrate metabolism. Prior work showed that myocardial inactivation of c-Myc (Myc) attenuated hypertrophy and decreased expression of metabolic genes after aortic constriction. Accordingly, we hypothesize that Myc regulates substrate preferences for the citric acid cycle during pressure overload hypertrophy from transverse aortic constriction (TAC) and that these metabolic changes impact cardiac function and growth. To test this hypothesis, we subjected mice with cardiac specific, inducible Myc inactivation (MycKO-TAC) and non-transgenic littermates (Cont-TAC) to transverse aortic constriction (TAC; n=7/group). A separate group underwent sham surgery (Sham, n=5). After two weeks, function was measured in isolated working hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketone bodies and unlabeled glucose and insulin. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. Compared to Sham, Cont-TAC had increased free fatty acid fractional contribution with a concurrent decrease in unlabeled (predominately glucose) contribution. The changes in free fatty acid and unlabeled fractional contributions were abrogated by Myc inactivation during TAC (MycKO-TAC). Additionally, protein posttranslational modification by O-GlcNAc was significantly greater in Cont-TAC versus both Sham andmore »
- Authors:
-
- Seattle Children's Research Institute, Seattle, WA (United States)
- Univ. of Washington, Seattle, WA (United States)
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
- Seattle Children's Research Institute, Seattle, WA (United States); Univ. of Washington, Seattle, WA (United States)
- Univ. Catholique de Louvain (Belgium)
- Publication Date:
- Research Org.:
- Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER)
- OSTI Identifier:
- 1229960
- Report Number(s):
- PNNL-SA-106577
Journal ID: ISSN 1932-6203; 48162; 600306000
- Grant/Contract Number:
- AC05-76RL01830
- Resource Type:
- Accepted Manuscript
- Journal Name:
- PLoS ONE
- Additional Journal Information:
- Journal Volume: 10; Journal Issue: 8; Journal ID: ISSN 1932-6203
- Publisher:
- Public Library of Science
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Environmental Molecular Sciences Laboratory; heart; fatty acids; glucose metabolism; citric acid cycle; glucose; protein metabolism; enzyme metabolism; oxidation
Citation Formats
Ledee, Dolena, Smith, Lincoln, Bruce, Margaret, Kajimoto, Masaki, Isern, Nancy, Portman, Michael A., Olson, Aaron K., and Bertrand, Luc. c-Myc alters substrate utilization and O-GlcNAc protein posttranslational modifications without altering cardiac function during early aortic constriction. United States: N. p., 2015.
Web. doi:10.1371/journal.pone.0135262.
Ledee, Dolena, Smith, Lincoln, Bruce, Margaret, Kajimoto, Masaki, Isern, Nancy, Portman, Michael A., Olson, Aaron K., & Bertrand, Luc. c-Myc alters substrate utilization and O-GlcNAc protein posttranslational modifications without altering cardiac function during early aortic constriction. United States. https://doi.org/10.1371/journal.pone.0135262
Ledee, Dolena, Smith, Lincoln, Bruce, Margaret, Kajimoto, Masaki, Isern, Nancy, Portman, Michael A., Olson, Aaron K., and Bertrand, Luc. Wed .
"c-Myc alters substrate utilization and O-GlcNAc protein posttranslational modifications without altering cardiac function during early aortic constriction". United States. https://doi.org/10.1371/journal.pone.0135262. https://www.osti.gov/servlets/purl/1229960.
@article{osti_1229960,
title = {c-Myc alters substrate utilization and O-GlcNAc protein posttranslational modifications without altering cardiac function during early aortic constriction},
author = {Ledee, Dolena and Smith, Lincoln and Bruce, Margaret and Kajimoto, Masaki and Isern, Nancy and Portman, Michael A. and Olson, Aaron K. and Bertrand, Luc},
abstractNote = {Pressure overload cardiac hypertrophy alters substrate metabolism. Prior work showed that myocardial inactivation of c-Myc (Myc) attenuated hypertrophy and decreased expression of metabolic genes after aortic constriction. Accordingly, we hypothesize that Myc regulates substrate preferences for the citric acid cycle during pressure overload hypertrophy from transverse aortic constriction (TAC) and that these metabolic changes impact cardiac function and growth. To test this hypothesis, we subjected mice with cardiac specific, inducible Myc inactivation (MycKO-TAC) and non-transgenic littermates (Cont-TAC) to transverse aortic constriction (TAC; n=7/group). A separate group underwent sham surgery (Sham, n=5). After two weeks, function was measured in isolated working hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketone bodies and unlabeled glucose and insulin. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. Compared to Sham, Cont-TAC had increased free fatty acid fractional contribution with a concurrent decrease in unlabeled (predominately glucose) contribution. The changes in free fatty acid and unlabeled fractional contributions were abrogated by Myc inactivation during TAC (MycKO-TAC). Additionally, protein posttranslational modification by O-GlcNAc was significantly greater in Cont-TAC versus both Sham and MycKO-TAC. Lastly, Myc alters substrate preferences for the citric acid cycle during early pressure overload hypertrophy without negatively affecting cardiac function. Myc also affects protein posttranslational modifications by O-GlcNAc during hypertrophy.},
doi = {10.1371/journal.pone.0135262},
journal = {PLoS ONE},
number = 8,
volume = 10,
place = {United States},
year = {Wed Aug 12 00:00:00 EDT 2015},
month = {Wed Aug 12 00:00:00 EDT 2015}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Cited by: 18 works
Citation information provided by
Web of Science
Web of Science
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Cardiac myocyte hypertrophy is associated with c-myc protooncogene expression.
journal, November 1986
- Starksen, N. F.; Simpson, P. C.; Bishopric, N.
- Proceedings of the National Academy of Sciences, Vol. 83, Issue 21
Cardiac myocyte hypertrophy is associated with c-myc protooncogene expression.
journal, November 1986
- Starksen, N. F.; Simpson, P. C.; Bishopric, N.
- Proceedings of the National Academy of Sciences, Vol. 83, Issue 21
Molecular characterization of angiotensin II--induced hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts. Critical role of the AT1 receptor subtype.
journal, September 1993
- Sadoshima, J.; Izumo, S.
- Circulation Research, Vol. 73, Issue 3
Cardiac Metabolism and its Interactions With Contraction, Growth, and Survival of Cardiomyocytes
journal, August 2013
- Kolwicz, Stephen C.; Purohit, Suneet; Tian, Rong
- Circulation Research, Vol. 113, Issue 5
Regulation of a Cytosolic and Nuclear O -GlcNAc Transferase : ROLE OF THE TETRATRICOPEPTIDE REPEATS
journal, November 1999
- Kreppel, Lisa K.; Hart, Gerald W.
- Journal of Biological Chemistry, Vol. 274, Issue 45
Cardiac-Specific Deletion of Acetyl CoA Carboxylase 2 Prevents Metabolic Remodeling During Pressure-Overload Hypertrophy
journal, August 2012
- Kolwicz, Stephen C.; Olson, David P.; Marney, Luke C.
- Circulation Research, Vol. 111, Issue 6
Inducible Activation of c-Myc in Adult Myocardium In Vivo Provokes Cardiac Myocyte Hypertrophy and Reactivation of DNA Synthesis
journal, December 2001
- Xiao, Guishan; Mao, Songyan; Baumgarten, Georg
- Circulation Research, Vol. 89, Issue 12
Reexpression of pyruvate kinase M2 in type 1 myofibers correlates with altered glucose metabolism in myotonic dystrophy
journal, July 2013
- Gao, Z.; Cooper, T. A.
- Proceedings of the National Academy of Sciences, Vol. 110, Issue 33
GLUT1 deficiency in cardiomyocytes does not accelerate the transition from compensated hypertrophy to heart failure
journal, July 2014
- Pereira, Renata O.; Wende, Adam R.; Olsen, Curtis
- Journal of Molecular and Cellular Cardiology, Vol. 72
Inducible Overexpression of GLUT1 Prevents Mitochondrial Dysfunction and Attenuates Structural Remodeling in Pressure Overload but Does Not Prevent Left Ventricular Dysfunction
journal, September 2013
- Pereira, Renata O.; Wende, Adam R.; Olsen, Curtis
- Journal of the American Heart Association, Vol. 2, Issue 5
Myocardial hypertrophy is not a prerequisite for changes in early gene expression in left ventricular volume overload
journal, February 2004
- Dzimiri, Nduna; Al-Bahnasi, Kholod; Al-Halees, Zohair
- Fundamental and Clinical Pharmacology, Vol. 18, Issue 1
Targeting myocardial substrate metabolism in heart failure: potential for new therapies
journal, February 2012
- Ardehali, Hossein; Sabbah, Hani N.; Burke, Michael A.
- European Journal of Heart Failure, Vol. 14, Issue 2
Myocardial Substrate Metabolism in the Normal and Failing Heart
journal, July 2005
- Stanley, William C.; Recchia, Fabio A.; Lopaschuk, Gary D.
- Physiological Reviews, Vol. 85, Issue 3
Studies on l-Glutamine d-Fructose 6-Phosphate Amidotransferase
journal, July 1967
- Kornfeld, Rosalind
- Journal of Biological Chemistry, Vol. 242, Issue 13
Transverse Aortic Constriction in Mice
journal, April 2010
- deAlmeida, Angela C.; van Oort, Ralph J.; Wehrens, Xander H. T.
- Journal of Visualized Experiments, Issue 38
Cardiac Metabolism in Heart Failure: Implications Beyond ATP Production
journal, August 2013
- Doenst, Torsten; Nguyen, Tien Dung; Abel, E. Dale
- Circulation Research, Vol. 113, Issue 6
A PKM2 signature in the failing heart
journal, April 2015
- Rees, Meredith L.; Subramaniam, Janani; Li, Yuanteng
- Biochemical and Biophysical Research Communications, Vol. 459, Issue 3
Protooncogene induction and reprogramming of cardiac gene expression produced by pressure overload.
journal, January 1988
- Izumo, S.; Nadal-Ginard, B.; Mahdavi, V.
- Proceedings of the National Academy of Sciences, Vol. 85, Issue 2
Thyroid Hormone Reverses Aging-Induced Myocardial Fatty Acid Oxidation Defects and Improves the Response to Acutely Increased Afterload
journal, June 2013
- Ledee, Dolena; Portman, Michael A.; Kajimoto, Masaki
- PLoS ONE, Vol. 8, Issue 6
Pressure-overload-induced heart failure induces a selective reduction in glucose oxidation at physiological afterload
journal, December 2012
- Zhabyeyev, Pavel; Gandhi, Manoj; Mori, Jun
- Cardiovascular Research, Vol. 97, Issue 4
Maintaining PGC‐1α expression following pressure overload‐induced cardiac hypertrophy preserves angiogenesis but not contractile or mitochondrial function
journal, April 2014
- Pereira, Renata O.; Wende, Adam R.; Crum, Ashley
- The FASEB Journal, Vol. 28, Issue 8
C-Myc induced compensated cardiac hypertrophy increases free fatty acid utilization for the citric acid cycle
journal, February 2013
- Olson, Aaron K.; Ledee, Dolena; Iwamoto, Kate
- Journal of Molecular and Cellular Cardiology, Vol. 55
Avoidance of Transient Cardiomyopathy in Cardiomyocyte-Targeted Tamoxifen-Induced MerCreMer Gene Deletion Models
journal, July 2009
- Koitabashi, Norimichi; Bedja, Djahida; Zaiman, Ari L.
- Circulation Research, Vol. 105, Issue 1
Acute Regulation of Cardiac Metabolism by the Hexosamine Biosynthesis Pathway and Protein O-GlcNAcylation
journal, April 2011
- Laczy, Boglárka; Fülöp, Norbert; Onay-Besikci, Arzu
- PLoS ONE, Vol. 6, Issue 4
Cardiac-Specific Overexpression of GLUT1 Prevents the Development of Heart Failure Attributable to Pressure Overload in Mice
journal, October 2002
- Liao, Ronglih; Jain, Mohit; Cui, Lei
- Circulation, Vol. 106, Issue 16
Myc controls transcriptional regulation of cardiac metabolism and mitochondrial biogenesis in response to pathological stress in mice
journal, May 2010
- Ahuja, Preeti; Zhao, Peng; Angelis, Ekaterini
- Journal of Clinical Investigation, Vol. 120, Issue 5
Protein O-linked β-N-acetylglucosamine: A novel effector of cardiomyocyte metabolism and function
journal, March 2012
- Darley-Usmar, Victor M.; Ball, Lauren E.; Chatham, John C.
- Journal of Molecular and Cellular Cardiology, Vol. 52, Issue 3
Contribution of various substrates to total citric acid cycle flux and ]anaplerosis as determined by13C isotopomer analysis and O2 consumption in the heart
journal, March 1996
- Malloy, Craig R.; Jones, John G.; Jeffrey, F. Mark
- MAGMA Magnetic Resonance Materials in Physics, Biology, and Medicine, Vol. 4, Issue 1
Thyroid Hormone Reverses Aging-Induced Myocardial Fatty Acid Oxidation Defects and Improves the Response to Acutely Increased Afterload
journal, June 2013
- Ledee, Dolena; Portman, Michael A.; Kajimoto, Masaki
- PLoS ONE, Vol. 8, Issue 6
PGC-1β Deficiency Accelerates the Transition to Heart Failure in Pressure Overload Hypertrophy
journal, September 2011
- Riehle, Christian; Wende, Adam R.; Zaha, Vlad G.
- Circulation Research, Vol. 109, Issue 7
Metabolic Remodeling in the Hypertrophic Heart
journal, August 2012
- Chatham, John C.; Young, Martin E.
- Circulation Research, Vol. 111, Issue 6
Cell Cycle Re-Entry and Mitochondrial Defects in Myc-Mediated Hypertrophic Cardiomyopathy and Heart Failure
journal, September 2009
- Lee, Hyoung-gon; Chen, Qun; Wolfram, Julie A.
- PLoS ONE, Vol. 4, Issue 9
Protooncogene induction and reprogramming of cardiac gene expression produced by pressure overload.
journal, January 1988
- Izumo, S.; Nadal-Ginard, B.; Mahdavi, V.
- Proceedings of the National Academy of Sciences, Vol. 85, Issue 2
Triidothyronine and epinephrine rapidly modify myocardial substrate selection: a 13 C isotopomer analysis
journal, November 2001
- Krueger, Julia J.; Ning, Xue-Han; Argo, Barisa M.
- American Journal of Physiology-Endocrinology and Metabolism, Vol. 281, Issue 5
Inducible Activation of c-Myc in Adult Myocardium In Vivo Provokes Cardiac Myocyte Hypertrophy and Reactivation of DNA Synthesis
journal, December 2001
- Xiao, Guishan; Mao, Songyan; Baumgarten, Georg
- Circulation Research, Vol. 89, Issue 12
Hypertrophic growth in cardiac myocytes is mediated by Myc through a Cyclin D2-dependent pathway
journal, August 2006
- Zhong, Weiguang; Mao, Songyan; Tobis, Scott
- The EMBO Journal, Vol. 25, Issue 16
The Failing Heart — An Engine Out of Fuel
journal, March 2007
- Neubauer, Stefan
- New England Journal of Medicine, Vol. 356, Issue 11
Change of c-Myc expression and cardiac hypertrophy in patients with aortic valve replacement
journal, April 2001
- Taketani, Satoshi; Sawa, Yoshiki; Ichikawa, Hajime
- The Annals of Thoracic Surgery, Vol. 71, Issue 4
Pyruvate kinase type M2 and its role in tumor growth and spreading
journal, August 2005
- Mazurek, Sybille; Boschek, C. Bruce; Hugo, Ferdinand
- Seminars in Cancer Biology, Vol. 15, Issue 4
HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer
journal, December 2009
- David, Charles J.; Chen, Mo; Assanah, Marcela
- Nature, Vol. 463, Issue 7279
Works referencing / citing this record:
The role of post‐translational modifications in cardiac hypertrophy
journal, April 2019
- Yan, Kaowen; Wang, Kun; Li, Peifeng
- Journal of Cellular and Molecular Medicine, Vol. 23, Issue 6
Glucose Metabolism in Cardiac Hypertrophy and Heart Failure
journal, June 2019
- Tran, Diem H.; Wang, Zhao V.
- Journal of the American Heart Association, Vol. 8, Issue 12
AMPK activation counteracts cardiac hypertrophy by reducing O-GlcNAcylation
journal, January 2018
- Gélinas, Roselle; Mailleux, Florence; Dontaine, Justine
- Nature Communications, Vol. 9, Issue 1
O‐GlcNAc Transferase Promotes Compensated Cardiac Function and Protein Kinase A O‐GlcNAcylation During Early and Established Pathological Hypertrophy From Pressure Overload
journal, June 2019
- Zhu, Wei‐Zhong; El‐Nachef, Danny; Yang, Xiulan
- Journal of the American Heart Association, Vol. 8, Issue 11
AMPK activation counteracts cardiac hypertrophy by reducing O-GlcNAcylation
journal, January 2018
- Gélinas, Roselle; Mailleux, Florence; Dontaine, Justine
- Nature Communications, Vol. 9, Issue 1
O-GlcNAcylation and cardiovascular disease
journal, April 2017
- Wright, JaLessa N.; Collins, Helen E.; Wende, Adam R.
- Biochemical Society Transactions, Vol. 45, Issue 2
The role of post‐translational modifications in cardiac hypertrophy
journal, April 2019
- Yan, Kaowen; Wang, Kun; Li, Peifeng
- Journal of Cellular and Molecular Medicine, Vol. 23, Issue 6
Glucose Metabolism in Cardiac Hypertrophy and Heart Failure
journal, June 2019
- Tran, Diem H.; Wang, Zhao V.
- Journal of the American Heart Association, Vol. 8, Issue 12