Mitochondrial defects and heterogeneous cytochrome<i>c</i>release after cardiac cold ischemia and reperfusion

Kuznetsov, Andrey V.; Schneeberger, Stefan; Seiler, R.; Brandacher, Gerald; Märk, Walter; Steurer, Wolfgang; Saks, Valdur; Usson, Yves; Margreiter, Raimund; Gnaiger, Erich

doi:10.1152/ajpheart.00701.2003

Cited by 155 publications

(149 citation statements)

References 53 publications

Supporting

Mentioning

142

Contrasting

Order By: Relevance

“…A cytochrome effect of <10% validates the integrity of the outer mitochondrial membrane (Kuznetsov et al. 2004). Final respirometry data were expressed as pmol O/(s μ g) mitochondria.…”

Section: Methodsmentioning

confidence: 99%

Alterations in fatty acid metabolism and sirtuin signaling characterize early type-2 diabetic hearts of fructose-fed rats

et al. 2017

View full text Add to dashboard Cite

Despite the fact that skeletal muscle insulin resistance is the hallmark of type‐2 diabetes mellitus (T2DM), inflexibility in substrate energy metabolism has been observed in other tissues such as liver, adipose tissue, and heart. In the heart, structural and functional changes ultimately lead to diabetic cardiomyopathy. However, little is known about the early biochemical changes that cause cardiac metabolic dysregulation and dysfunction. We used a dietary model of fructose‐induced T2DM (10% fructose in drinking water for 6 weeks) to study cardiac fatty acid metabolism in early T2DM and related signaling events in order to better understand mechanisms of disease. In early type‐2 diabetic hearts, flux through the fatty acid oxidation pathway was increased as a result of increased cellular uptake (CD36), mitochondrial uptake (CPT1B), as well as increased β‐hydroxyacyl‐CoA dehydrogenase and medium‐chain acyl‐CoA dehydrogenase activities, despite reduced mitochondrial mass. Long‐chain acyl‐CoA dehydrogenase activity was slightly decreased, resulting in the accumulation of long‐chain acylcarnitine species. Cardiac function and overall mitochondrial respiration were unaffected. However, evidence of oxidative stress and subtle changes in cardiolipin content and composition were found in early type‐2 diabetic mitochondria. Finally, we observed decreased activity of SIRT1, a pivotal regulator of fatty acid metabolism, despite increased protein levels. This indicates that the heart is no longer capable of further increasing its capacity for fatty acid oxidation. Along with increased oxidative stress, this may represent one of the earliest signs of dysfunction that will ultimately lead to inflammation and remodeling in the diabetic heart.

show abstract

“…A cytochrome effect of <10% validates the integrity of the outer mitochondrial membrane (Kuznetsov et al. 2004). Final respirometry data were expressed as pmol O/(s μ g) mitochondria.…”

Section: Methodsmentioning

confidence: 99%

Alterations in fatty acid metabolism and sirtuin signaling characterize early type-2 diabetic hearts of fructose-fed rats

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The technology employs sensitive polarographic oxygen sensors to accurately measure O 2 flux under controlled conditions of temperature, ionic concentration, and substrate supply (7,33). A carefully designed sequence of substrate, uncoupler, and inhibitor titration (SUIT) protocols makes the assessment of rates of O 2 consumption at desired respiratory states possible (39,53). For example, in intact cells it is possible to determine the physiological resting respiration (ROUTINE respiration), uncoupled respiration (by inhibiting ATP synthase), and experimentally noncoupled respiration (by titrating nonphysiological uncouplers) (71).…”

Section: Use Of Respirometry For Assessment Of ␤-Oxidationmentioning

confidence: 99%

Measurement of β-oxidation capacity of biological samples by respirometry: a review of principles and substrates

Ojuka

Andrew

Bezuidenhout

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Oxidation of fatty acids is a major source of energy in the heart, liver, and skeletal muscle. It can be measured accurately using respirometry in isolated mitochondria, intact cells, and permeabilized cells or tissues. This technique directly measures the rate of oxygen consumption or flux at various respiratory states when appropriate substrates, uncouplers, and inhibitors are used. Acylcarnitines such as palmitoylcarnitine or octanoylcarnitine are the commonly used substrates. The β-oxidation pathway is prone to feedforward inhibition resulting from accumulation of short-chain acyl-CoA and depletion of CoA, but inclusion of malate or carnitine prevents accumulation of these intermediaries and CoA depletion.

show abstract

“…13 Bcl-xL was also reported to inhibit Bax translocation to the mitochondria, decrease the release of cytochrome c (cyto-c) from the mitochondria to the cytosol, and protect retinal cell apoptosis in transgenic mice. 14 Because cold ischemia and reperfusion cause mitochondrial dysfunction and release of cyto-c from the mitochondria to the cytosol, 15 we hypothesized that Bcl-xL would be useful in preventing cold ischemia and warm reperfusion injury of the heart.…”

Section: See Pmentioning

confidence: 99%

Bcl-xL Gene Transfer Inhibits Bax Translocation and Prolongs Cardiac Cold Preservation Time in Rats

et al. 2005

View full text Add to dashboard Cite

Background-Apoptosis is an important cause of early graft loss after heart transplantation. Bcl-xL was reported to protect the heart against normothermic ischemia and reperfusion injury. In this study, we determined whether overexpression of Bcl-xL could inhibit tissue injury resulting from prolonged cold preservation followed by warm reperfusion of heart transplants. Methods and Results-Lewis rat hearts were transduced with an adenovirus vector harboring Bcl-xL cDNA (AxCAhBclxL) 4 days before collection of tissue. After preservation in University of Wisconsin solution at 4°C for 24 hours, the heart was either perfused with a Langendorff device ex vivo or used for heterotopic heart transplantation in vivo. Bcl-xL gene transfer significantly reduced the infarct size (23.0Ϯ2.6% versus 47.7Ϯ7.0% in saline control and 48.6Ϯ6.1% in vector control, PϽ0.01) after 2-hour reperfusion at 37°C with the Langendorff device and significantly decreased creatine kinase release (0.82Ϯ0.27 IU, versus 1.57Ϯ0.33 and 1.50Ϯ0.37 IU in saline and vector controls, respectively; PϽ0.05). In heart transplantation, overexpresson of Bcl-xL inhibited Bax translocation from the cytosol to the mitochondria, resulting in decreased cytochrome c release from the mitochondria; it also significantly decreased cardiac cell apoptosis and improved graft survival rate after long cold preservation, followed by warm reperfusion. Conclusions-Bcl-xL

show abstract

Mitochondrial defects and heterogeneous cytochromecrelease after cardiac cold ischemia and reperfusion

Cited by 155 publications

References 53 publications

Alterations in fatty acid metabolism and sirtuin signaling characterize early type-2 diabetic hearts of fructose-fed rats

Alterations in fatty acid metabolism and sirtuin signaling characterize early type-2 diabetic hearts of fructose-fed rats

Measurement of β-oxidation capacity of biological samples by respirometry: a review of principles and substrates

Bcl-xL Gene Transfer Inhibits Bax Translocation and Prolongs Cardiac Cold Preservation Time in Rats

Contact Info

Product

Resources

About