An increase in the myocardial PCr/ATP ratio in GLUT4 null mice.

Robert G. Weiss, John C. Chatham, Dimitrios Georgakopolous, Maureen J. Charron, Theo Wallimann, Laurence Kay, Bernd Walzel, Yibin Wang, David A. Kass, Gary Gerstenblith, V. P. Chacko

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

ATP and creatine phosphate (PCr) are prime myocardial high-energy phosphates. Their relative concentrations are conserved among mammalian species and across a range of physiologic cardiac workloads. The cardiac PCr/ATP ratio is decreased with several pathologic conditions, such as ischemia and heart failure, but there are no reports of an increase in the cardiac PCr/ATP ratio in any species or with interventions. We studied the in vivo energetics in transgenic mice lacking expression of the glucose transport protein GLUT4 (G4N) and observed a significant 60% increase in the myocardial PCr/ATP ratio in G4N that was confirmed in three different experimental settings including intact animals. The higher PCr/ATP in G4N is cardiac-specific and is due to higher total cardiac creatine (CR) concentrations in G4N than in wild-type (WT). However, [ATP], [ADP], and -DG(-ATP) did not differ between the strains. Expression of the creatine transport protein (CreaT) that is responsible for creatine uptake in myocytes was preserved in G4N cardiac tissue. These observations demonstrate, for the first time to our knowledge, that G4N manifest a unique increase in the cardiac PCr/ATP ratio, which suggests a novel genetic strategy for increasing myocardial creatine levels.

Original languageEnglish (US)
Pages (from-to)613-615
Number of pages3
JournalThe FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume16
Issue number6
StatePublished - 2002
Externally publishedYes

Fingerprint

Adenosine Triphosphate
Creatine
Phosphocreatine
Facilitative Glucose Transport Proteins
Workload
Adenosine Diphosphate
Muscle Cells
Transgenic Mice
Carrier Proteins
Animals
Ischemia
Heart Failure
Phosphates
Tissue

Cite this

An increase in the myocardial PCr/ATP ratio in GLUT4 null mice. / Weiss, Robert G.; Chatham, John C.; Georgakopolous, Dimitrios; Charron, Maureen J.; Wallimann, Theo; Kay, Laurence; Walzel, Bernd; Wang, Yibin; Kass, David A.; Gerstenblith, Gary; Chacko, V. P.

In: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol. 16, No. 6, 2002, p. 613-615.

Research output: Contribution to journalArticle

Weiss, RG, Chatham, JC, Georgakopolous, D, Charron, MJ, Wallimann, T, Kay, L, Walzel, B, Wang, Y, Kass, DA, Gerstenblith, G & Chacko, VP 2002, 'An increase in the myocardial PCr/ATP ratio in GLUT4 null mice.', The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, vol. 16, no. 6, pp. 613-615.
Weiss, Robert G. ; Chatham, John C. ; Georgakopolous, Dimitrios ; Charron, Maureen J. ; Wallimann, Theo ; Kay, Laurence ; Walzel, Bernd ; Wang, Yibin ; Kass, David A. ; Gerstenblith, Gary ; Chacko, V. P. / An increase in the myocardial PCr/ATP ratio in GLUT4 null mice. In: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2002 ; Vol. 16, No. 6. pp. 613-615.
@article{c5466f213da545cf843c9afaee68dd7f,
title = "An increase in the myocardial PCr/ATP ratio in GLUT4 null mice.",
abstract = "ATP and creatine phosphate (PCr) are prime myocardial high-energy phosphates. Their relative concentrations are conserved among mammalian species and across a range of physiologic cardiac workloads. The cardiac PCr/ATP ratio is decreased with several pathologic conditions, such as ischemia and heart failure, but there are no reports of an increase in the cardiac PCr/ATP ratio in any species or with interventions. We studied the in vivo energetics in transgenic mice lacking expression of the glucose transport protein GLUT4 (G4N) and observed a significant 60{\%} increase in the myocardial PCr/ATP ratio in G4N that was confirmed in three different experimental settings including intact animals. The higher PCr/ATP in G4N is cardiac-specific and is due to higher total cardiac creatine (CR) concentrations in G4N than in wild-type (WT). However, [ATP], [ADP], and -DG(-ATP) did not differ between the strains. Expression of the creatine transport protein (CreaT) that is responsible for creatine uptake in myocytes was preserved in G4N cardiac tissue. These observations demonstrate, for the first time to our knowledge, that G4N manifest a unique increase in the cardiac PCr/ATP ratio, which suggests a novel genetic strategy for increasing myocardial creatine levels.",
author = "Weiss, {Robert G.} and Chatham, {John C.} and Dimitrios Georgakopolous and Charron, {Maureen J.} and Theo Wallimann and Laurence Kay and Bernd Walzel and Yibin Wang and Kass, {David A.} and Gary Gerstenblith and Chacko, {V. P.}",
year = "2002",
language = "English (US)",
volume = "16",
pages = "613--615",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "6",

}

TY - JOUR

T1 - An increase in the myocardial PCr/ATP ratio in GLUT4 null mice.

AU - Weiss, Robert G.

AU - Chatham, John C.

AU - Georgakopolous, Dimitrios

AU - Charron, Maureen J.

AU - Wallimann, Theo

AU - Kay, Laurence

AU - Walzel, Bernd

AU - Wang, Yibin

AU - Kass, David A.

AU - Gerstenblith, Gary

AU - Chacko, V. P.

PY - 2002

Y1 - 2002

N2 - ATP and creatine phosphate (PCr) are prime myocardial high-energy phosphates. Their relative concentrations are conserved among mammalian species and across a range of physiologic cardiac workloads. The cardiac PCr/ATP ratio is decreased with several pathologic conditions, such as ischemia and heart failure, but there are no reports of an increase in the cardiac PCr/ATP ratio in any species or with interventions. We studied the in vivo energetics in transgenic mice lacking expression of the glucose transport protein GLUT4 (G4N) and observed a significant 60% increase in the myocardial PCr/ATP ratio in G4N that was confirmed in three different experimental settings including intact animals. The higher PCr/ATP in G4N is cardiac-specific and is due to higher total cardiac creatine (CR) concentrations in G4N than in wild-type (WT). However, [ATP], [ADP], and -DG(-ATP) did not differ between the strains. Expression of the creatine transport protein (CreaT) that is responsible for creatine uptake in myocytes was preserved in G4N cardiac tissue. These observations demonstrate, for the first time to our knowledge, that G4N manifest a unique increase in the cardiac PCr/ATP ratio, which suggests a novel genetic strategy for increasing myocardial creatine levels.

AB - ATP and creatine phosphate (PCr) are prime myocardial high-energy phosphates. Their relative concentrations are conserved among mammalian species and across a range of physiologic cardiac workloads. The cardiac PCr/ATP ratio is decreased with several pathologic conditions, such as ischemia and heart failure, but there are no reports of an increase in the cardiac PCr/ATP ratio in any species or with interventions. We studied the in vivo energetics in transgenic mice lacking expression of the glucose transport protein GLUT4 (G4N) and observed a significant 60% increase in the myocardial PCr/ATP ratio in G4N that was confirmed in three different experimental settings including intact animals. The higher PCr/ATP in G4N is cardiac-specific and is due to higher total cardiac creatine (CR) concentrations in G4N than in wild-type (WT). However, [ATP], [ADP], and -DG(-ATP) did not differ between the strains. Expression of the creatine transport protein (CreaT) that is responsible for creatine uptake in myocytes was preserved in G4N cardiac tissue. These observations demonstrate, for the first time to our knowledge, that G4N manifest a unique increase in the cardiac PCr/ATP ratio, which suggests a novel genetic strategy for increasing myocardial creatine levels.

UR - http://www.scopus.com/inward/record.url?scp=0036546234&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036546234&partnerID=8YFLogxK

M3 - Article

VL - 16

SP - 613

EP - 615

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 6

ER -