52 research outputs found
Skeletal Muscle Mitochondrial Function in Peripheral Arterial Disease: Usefulness of Muscle Biopsy
Diabetes Worsens Skeletal Muscle Mitochondrial Function, Oxidative Stress, and Apoptosis After Lower-Limb Ischemia-Reperfusion: Implication of the RISK and SAFE Pathways?
Objectives: Diabetic patients respond poorly to revascularization for peripheral arterial disease (PAD) but the underlying mechanisms are not well understood. We aimed to determine whether diabetes worsens ischemia-reperfusion (IR)-induced muscle dysfunction and the involvement of endogenous protective kinases in this process.
Materials and Methods: Streptozotocin-induced diabetic and non-diabetic rats were randomized to control or to IR injury (3 h of aortic cross-clamping and 2 h of reperfusion). Mitochondrial respiration, reactive oxygen species (ROS) production, protein levels of superoxide dismutase (SOD2) and endogenous protective kinases (RISK and SAFE pathways) were investigated in rat gastrocnemius, together with upstream (GSK-3β) and downstream (cleaved caspase-3) effectors of apoptosis.
Results: Although already impaired when compared to non-diabetic controls at baseline, the decline in mitochondrial respiration after IR was more severe in diabetic rats. In diabetic animals, IR-triggered oxidative stress (increased ROS production and reduced SOD2 levels) and effectors of apoptosis (reduced GSK-3β inactivation and higher cleaved caspase-3 levels) were increased to a higher level than in the non-diabetics. IR had no effect on the RISK pathway in non-diabetics and diabetic rats, but increased STAT 3 only in the latter.
Conclusion: Type 1 diabetes worsens IR-induced skeletal muscle injury, endogenous protective pathways not being efficiently stimulated
Mitochondrial physiology
As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery
Mitochondrial physiology
As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery
Local but not systemic capillary lactate is a reperfusion biomarker in experimental acute limb ischaemia
Systemic capillary lactate, an end product of cellular anaerobic metabolism, has not established credibility in monitoring limb reperfusion. We assessed, in mice, whether local capillary lactate, arising from the reperfused limb, might be a relevant biomarker of reperfusion.; Systemic and local capillary lactate were sampled in the non-ischaemic and in the ischaemic limb. Only local lactate concentrations significantly increased after 2 h of ischaemia and decreased after reperfusion.; Local, but not systemic, capillary lactate appeared as a potential reperfusion biomarker in this experimental acute limb ischaemia model
Apparent Km of mitochondria for oxygen computed from Vmax measured in permeabilized muscle fibers is lower in water enriched in oxygen by electrolysis than injection
Joffrey Zoll,1 Jamal Bouitbir,1 Pascal Sirvent,2 Alexis Klein,3 Antoine Charton,1,4 Liliana Jimenez,3 François R Péronnet,5 Bernard Geny,1 Ruddy Richard61Physiology Department, Faculty of Medicine and EA3072, Université de Strasbourg, Strasbourg, 2Clermont Université, Université Blaise Pascal, EA 3533, Laboratoire des Adaptations Métaboliques à l’Exercice en Conditions Physiologiques et Pathologiques, Clermont-Ferrand, 3Danone Research, Centre Daniel Carasso, Palaiseau, 4Department of Anesthesia and Critical Care and EA3072, Hôpital de Hautepierre, Université de Strasbourg, France; 5Kinesiology Department, Université de Montréal, Montréal, QC, Canada; 6Department of Sport Medicine and Functional Explorations and INRA UMR 1019, Faculty of Medicine, Université d’Auvergne, Clermont-Ferrand, FranceBackground: It has been suggested that oxygen (O2) diffusion could be favored in water enriched in O2 by a new electrolytic process because of O2 trapping in water superstructures (clathrates), which could reduce the local pressure/content relationships for O2 and facilitate O2 diffusion along PO2 gradients.Materials and methods: Mitochondrial respiration was compared in situ in saponin-skinned fibers isolated from the soleus muscles of Wistar rats, in solution enriched in O2 by injection or the electrolytic process 1) at an O2 concentration decreasing from 240 µmol/L to 10 µmol/L (132 mmHg to 5 mmHg), with glutamate–malate or N, N, N', N'-tetramethyl-p-phenylenediamine dihydrochloride (TMPD)–ascorbate (with antimycin A) as substrates; and 2) at increasing adenosine diphosphate (ADP) concentration with glutamate–malate as substrate.Results: As expected, maximal respiration decreased with O2 concentration and, when compared to glutamate–malate, the apparent Km O2 of mitochondria for O2 was significantly lower with TMPD–ascorbate with both waters. However, when compared to the water enriched in O2 by injection, the Km O2 was significantly lower with both electron donors in water enriched in O2 by electrolysis. This was not associated with any increase in the sensitivity of mitochondria to ADP; no significant difference was observed for the Km ADP between the two waters.Conclusion: In this experiment, a higher affinity of the mitochondria for O2 was observed in water enriched in O2 by electrolysis than by injection. This observation is consistent with the hypothesis that O2 diffusion can be facilitated in water enriched in O2 by the electrolytic process.Keywords: saponin-skinned fibers, mitochondrial respiration, glutamate–malate, TMPD–ascorbate, Km O
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