The heart requires large amount of energy to support
its constant contractions and other physiological activities. Due to the high
energy demand of the heart to function, cardiomyocytes have high mitochondrial
density with it taking up over 35% of total cell volume as compared to other
tissues besides their ability to metabolize a wide range of energy substrates
including carbohydrates, lipids, amino acids and ketone bodies to meet their
energy requirements1,
2. It is well established
that the energy metabolism of cardiomyocytes are tightly regulated and changes
as they mature; where initially the fetal cardiomyocytes are highly dependent
on glycolysis for energy which later on switch to fatty acid b-oxidation when they mature and
become  differentiated as seen in adult
cardiomyocytes3. Interestingly, the metabolism of mature cardiomyocytes will
switch back to glycolysis as their energy source if hypertrophic stress
develops4-6. By monitoring the expression of genes involved in these
metabolic pathways of glycolysis and b-oxidation could be used to study the changes and identify the
maturation/disease stage in which the cardiomyocyte is in.

 

In humans, the accumulation of oxidative stress
results in cardiac hypertrophy and diseased cardiomyocytes. Hypertrophy causes
the cardiomyocytes to revert to the glycolysis-dependent fetal-like form,
weakening the contraction of the heart. This also occurs during the natural
process of ageing. Antioxidants, including Vitamin C, have been proven to slow
down the progression of ageing by neutralising free radicals responsible for
this7. Henceforth, in this proposal, we
aim to investigate the beneficial effects of tocotrienol compounds
(anti-oxidants) in promoting cardiomyocyte maturation and/or protection against
cardiac hypertrophy using a human glycolysis metabolic reporter cell line. This metabolic reporter system will reflect changes in
metabolic pathways (glycolysis vs b-oxidation), thereby
allowing us to track the cellular status of cardiomyocytes (fetal-like, mature
or undergoing cardiac hypertrophy) by quantitating the usage of different
metabolic pathways based on colorimetric analysis.

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