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Viral Transgene Expression in Rodent Hearts and the Assessment of Cardiac Arrhythmia Risk
Published on: July 27, 2022
Creatine uptake in mouse hearts with genetically altered creatine levels
Michiel ten Hove1, Kimmo Makinen, Liam Sebag-Montefiore
1Department of Cardiovascular Medicine, University of Oxford, Oxford, UK. michiel.tenhove@gmail.com
Journal of Molecular and Cellular Cardiology
|July 8, 2008
Summary
Heart creatine uptake can increase significantly, but is regulated by feedback inhibition. This suggests creatine transporter activity is mainly controlled by factors other than gene expression changes.
Area of Science:
- Biochemistry
- Cardiovascular Physiology
- Molecular Biology
Background:
- Creatine is vital for heart energy metabolism.
- The creatine transporter (CrT) regulates creatine uptake in cardiomyocytes.
- Reduced CrT capacity lowers myocardial creatine in heart failure.
Purpose of the Study:
- Investigate the regulation of the myocardial creatine transporter (CrT).
- Understand how altered creatine levels affect CrT activity and expression.
- Examine feedback mechanisms controlling cardiac creatine uptake.
Main Methods:
- Utilized guanidinoacetate-N-methyl transferase knockout (GAMT(-/-)) mice and CrT-overexpressing (CrT-OE) mice.
- Measured cardiac creatine uptake using (14)C-radiolabeled creatine in isolated hearts.
- Assessed CrT mRNA levels via real-time RT-PCR and creatine content using HPLC.
Main Results:
- GAMT(-/-) mouse hearts exhibited a 7-fold increase in creatine uptake V(max) and a 1.4-fold increase in CrT mRNA.
- Dietary creatine supplementation largely prevented these increases, indicating negative feedback.
- CrT-OE mouse hearts showed a 2.7-fold average increase in creatine uptake, with significant variation.
- Total CrT mRNA levels correlated with myocardial creatine content, but endogenous levels did not.
Conclusions:
- Cardiac creatine uptake can be upregulated nearly tenfold and is subject to feedback inhibition.
- CrT activity appears predominantly regulated by mechanisms independent of gene expression changes.
- These findings offer insights into myocardial creatine homeostasis and potential therapeutic targets.
