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Anderson 2011 Am J Physiol Heart Circ Physiol
Additional label Spectrofluorometry  +
Coupling states OXPHOS  + , ET  +
Diseases Diabetes  +
Has abstract Progressive energy deficiency and loss of
Progressive energy deficiency and loss of cardiomyocyte numbers are two prominent factors that lead to heart failure in experimental models. Signals which mediate cardiomyocyte cell death have been suggested to come from both extrinsic (e.g. cytokines) and intrinsic (e.g. mitochondria) sources, but the evidence supporting these mechanisms remain unclear, and virtually non-existent in humans. In this study, we investigated the sensitivity of the mitochondrial permeability transition pore (mtPTP) to calcium (Ca<sup>2+</sup>) using permeabilized myofibers of right atrium obtained from diabetic (''N'' = 9) and non-diabetic (''N'' = 12) patients with coronary artery disease undergoing non-emergent coronary revascularization surgery. Under conditions that mimic the energetic state of the heart ''in vivo'' (pyruvate, glutamate, malate and 100 μM ADP), cardiac mitochondria from diabetic patients show an increased sensitivity to Ca<sup>2+</sup>-induced mtPTP opening as compared to non-diabetic patients. This increased mtPTP Ca<sup>2+</sup>-sensitivity in diabetic heart mitochondria is accompanied by a substantially greater rate of mitochondrial H<sub>2</sub>O<sub>2</sub> emission (mtH<sub>2</sub>O<sub>2</sub>) under identical conditions, despite no differences in respiratory capacity under these conditions or mitochondrial enzyme content. Activity of the intrinsic apoptosis-pathway mediator, caspase-9, was greater in diabetic atrial tissue, while activity of the extrinsic-pathway mediator, caspase-8, was unchanged between groups. Furthermore, caspase-3 activity was not significantly increased in diabetic atrial tissue. These data collectively suggest that the myocardium in diabetic patients has a greater overall propensity for mitochondrial-dependent cell death, possibly as a result of metabolic stress-imposed changes that have occurred within the mitochondria, rendering them more susceptible to insults such as Ca<sup>2+</sup> overload. In addition, they lend further support to the notion that mitochondria represent a viable target for future therapies directed at ameliorating heart failure and other co-morbidities that come with diabetes.
er co-morbidities that come with diabetes.  +
Has info [http://www.ncbi.nlm.nih.gov/pubmed/21076025 PMID: 21076025 Open Access]  +
Has publicationkeywords Ca<sup>2+</sup>  + , H<sub>2</sub>O<sub>2</sub>  + , mt-Permeability transition  +
Has title Anderson EJ, Rodriguez E, Anderson CA, Thayne K, Chitwood WR, Kypson AP (2011) Increased propensity for cell death in diabetic human heart is mediated by mitochondrial-dependent pathways. Am J Physiol Heart Circ Physiol 300:H118-24.  +
Instrument and method Oxygraph-2k  +
Mammal and model Human  +
Preparation Permeabilized tissue  +
Stress Oxidative stress;RONS  +
Tissue and cell Heart  +
Was published by MiPNetLab US NC Greenville Anderson EJ +
Was published in journal Am J Physiol Heart Circ Physiol +
Was published in year 2011  +
Was written by Anderson EJ + , Rodriguez E + , Anderson CA + , Thayne K + , Chitwood WR + , Kypson AP +
Categories Publications
Modification date
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08:59:33, 23 January 2019  +
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