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Huisamen 2015 Abstract MiPschool Cape Town 2015
Diseases Cardiovascular  +
Has abstract According to the latest statistics, variou
According to the latest statistics, various cardiovascular diseases accounted for 8.3% of natural deaths in South Africa during 2013, ranking the 6th place as cause of mortality. With the efficiency of therapies aimed at decreasing mortality from heart disease, life expectancy increased. As result of this, the focus of recent research changed towards understanding the energy demands of the heart in order to optimize function. Because of its high energetic needs, the human heart utilizes between 3.5 and 6 kg of ATP per day to function. This is produced by its mitochondrial populations which occupy up to 50% of the volume of a cardiomyocyte. A close link therefore exists between mitochondrial dysfunction and heart disease. In addition, there is growing recognition that inborn errors of metabolism can influence cardiomyocyte dysfunction [1] and that primary inherited mitochondrial diseases display a full spectrum of cardiac disorders [2]. ATM is a 350kDa serine/threonine protein kinase displaying homologies to the large protein family of PI3-Kinases, although it lacks the ability to phosphorylate lipids [3]. It came under scrutiny because of the disease, Ataxia-telangiectasie (A-T), which is an autosomal, recessive disorder that progressively affects multiple organs. This disease is caused by mutations in the Atm gene, resulting in lack or inactivation of the ATM protein [4]. ATM in the cell can be localized to the nucleus, cytoplasm of mitochondria. We became interested in myocardial ATM because it was found that skeletal muscle of insulin resistant, obese rats had dramatically reduced levels of the so-called ATM protein, in association with the well-known reduced activation of the insulin/ phosphatidylinositol 3 kinases (PI3- kinase)/PKB/Akt pathway, which is the main mechanism of relaying the metabolic effects of insulin [5]. Foster et al [6] found structural and functional changes in the hearts of ATM KO mice, using echocardiography and Doppler echocardiography. The mitochondrial association of ATM protein kinase plays an important role in its integrity and functioning such that ATM deficiency results in defects in mitochondrial respiration [7]. ATM also regulates mitochondrial biogenesis and DNA content [8]. In addition, it was demonstrated that a mitochondria-targeted antioxidant MitoQ, could decrease the features of the metabolic syndrome in ATM+/-ApoE-/- mice [9]. This may be because one of the mechanisms known to activate the ATM protein is increased oxidative stress. Activated ATM initiates an anti-oxidant response based on a metabolic shift while, in fibroblast cell lines, inactivation of ATM is associated with increased ROS levels followed by expression and activation of the transcription factor HIF-1alpha [10].
the transcription factor HIF-1alpha [10].  +
Has title The ATM protein and myocardial mitochondria.  +
MiP area Patients  + , mt-Awareness  +
Was submitted in year 2015  +
Was submitted to event MiPschool Cape Town 2015 +
Was written by Huisamen B +
Categories Abstracts
Modification date
"Modification date" is a predefined property that corresponds to the date of the last modification of a subject and is provided by Semantic MediaWiki.
08:35:22, 23 March 2015  +
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