Search results for "Bioenergetics"
showing 10 items of 88 documents
The Link between Oxidative Stress, Redox Status, Bioenergetics and Mitochondria in the Pathophysiology of ALS
2021
Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease of the motor system. It is characterized by the degeneration of both upper and lower motor neurons, which leads to muscle weakness and paralysis. ALS is incurable and has a bleak prognosis, with median survival of 3–5 years after the initial symptomatology. In ALS, motor neurons gradually degenerate and die. Many features of mitochondrial dysfunction are manifested in neurodegenerative diseases, including ALS. Mitochondria have shown to be an early target in ALS pathophysiology and contribute to disease progression. Disruption of their axonal transport, excessive generation of reactive oxygen species, disruptio…
New evidence for the multiplicity of ubiquinone- and inhibitor-binding sites in the mitochondrial complex I.
2000
Determination of the number of ubiquinone- and inhibitor-binding sites in the mitochondrial complex I (NADH:ubiquinone oxidoreductase) is a controversial question with a direct implication for elaborating a suitable model to explain the bioenergetic mechanism of this complicated enzyme. We have used combinations of both selective inhibitors and common ubiquinone-like substrates to demonstrate the multiplicity of the reaction centers in the complex I in contrast with competition studies that have suggested the existence of a unique binding site for ubiquinone. Our results provide new evidence for the existence of at least two freely exchangeable ubiquinone-binding sites with different specif…
Stable bioenergetic status despite substantial changes in blood flow and tissue oxygenation in a rat tumour.
1994
Experiments on s.c. rat tumours (DS sarcoma) were performed to determine whether chronic or acute changes in tumour perfusion necessarily lead to changes in tissue oxygenation and bioenergetic status since, as a rule, blood flow is thought to be the ultimate determinant of the tumour bioenergetic status. Based on this study, there is clear experimental evidence that growth-related or acute (following i.v. administration of tumour necrosis factor alpha) decreases in tumour blood flow are accompanied by parallel alterations in tissue oxygenation. In contrast, tumour energy status remains stable as long as flow values do not fall below 0.4-0.5 ml g-1 min-1, and provided that glucose as the mai…
Microregional distributions of glucose, lactate, ATP and tissue pH in experimental tumours upon local hyperthermia and/or hyperglycaemia
1993
Microregional distributions of glucose, lactate and ATP concentrations as well as tissue pH values were determined in subcutaneous rat tumours during normothermia and normoglycaemia, and upon local hyperthermia (HT) and/or hyperglycaemia (HG). Experiments were performed in order to investigate whether, and to what extent, these adjuvant therapeutic measures applied alone or in combination can modify the bioenergetic and metabolic status, parameters that are known to markedly influence the therapeutic response of tumours to heat. Local HT was performed in a saline bath (44 degrees C/2 h) and HG was induced by i.v. infusion of glucose for 2.5 h (blood glucose levels during heating: 35-40 mM).…
Cannabinoid control of brain bioenergetics: Exploring the subcellular localization of the CB1 receptor
2014
Brain mitochondrial activity is centrally involved in the central control of energy balance. When studying mitochondrial functions in the brain, however, discrepant results might be obtained, depending on the experimental approaches. For instance, immunostaining experiments and biochemical isolation of organelles expose investigators to risks of false positive and/or false negative results. As an example, the functional presence of cannabinoid type 1 (CB1) receptors on brain mitochondrial membranes (mtCB1) was recently reported and rapidly challenged, claiming that the original observation was likely due to artifact results. Here, we addressed this issue by directly comparing the procedures…
May the force be with you: Transfer of healthy mitochondria from stem cells to stroke cells
2018
Stroke is a major cause of death and disability in the United States and around the world with limited therapeutic option. Here, we discuss the critical role of mitochondria in stem cell-mediated rescue of stroke brain by highlighting the concept that deleting the mitochondria from stem cells abolishes the cells’ regenerative potency. The application of innovative approaches entailing generation of mitochondria-voided stem cells as well as pharmacological inhibition of mitochondrial function may elucidate the mechanism underlying transfer of healthy mitochondria to ischemic cells, thereby providing key insights in the pathology and treatment of stroke and other brain disorders plagued with…
Vascularization, Blood Flow, Oxygenation, Tissue pH, and Bioenergetic Status of Human Breast Cancer
1997
Many solid tumors are relatively resistant to conventional irradiation, chemotherapy and other non-surgical treatment modalities. A variety of factors are involved in the lack of responsiveness of these neoplasms, including (a) an intrinsic, genetically determined resistance and (b) physiological properties primarily created by inadequate and non-uniform vascular networks. Physiological factors which are usually closely linked encompass microcirculatory parameters (including transvascular and interstitial transport), tissue oxygen and nutrient supply, tumor pH and bioenergetic status. Despite the important role of physiological properties for tumor growth and metastasis, for early tumor res…
Manipulating mtDNA in vivo reprograms metabolism via novel response mechanisms.
2019
Mitochondria have been increasingly recognized as a central regulatory nexus for multiple metabolic pathways, in addition to ATP production via oxidative phosphorylation (OXPHOS). Here we show that inducing mitochondrial DNA (mtDNA) stress in Drosophila using a mitochondrially-targeted Type I restriction endonuclease (mtEcoBI) results in unexpected metabolic reprogramming in adult flies, distinct from effects on OXPHOS. Carbohydrate utilization was repressed, with catabolism shifted towards lipid oxidation, accompanied by elevated serine synthesis. Cleavage and translocation, the two modes of mtEcoBI action, repressed carbohydrate rmetabolism via two different mechanisms. DNA cleavage activ…
Improved growth performance in rainbow trout Oncorhynchus mykiss reared at high densities is linked to increased energy retention
2015
Abstract Behaviour has been suggested as an underlying factor influencing how rearing density affects growth performance in Salmonid fishes. At low densities there is an elevated intensity of aggressive interactions and the formation of dominance hierarchies. As density increases, it is commonly assumed that aggression decreases, as the cost and effort required to establish and maintain dominance hierarchies increase. The increased energy expenditure associated with aggressive interactions has been identified as one mechanism causing a reduced efficiency in feed utilisation and therefore decreased growth performance. Manipulating aggressive behaviour through density may have advantages from…
Galectin-3 Impairment of MYCN-Dependent Apoptosis-Sensitive Phenotype Is Antagonized by Nutlin-3 in Neuroblastoma Cells
2012
MYCN amplification occurs in about 20-25% of human neuroblastomas and characterizes the majority of the high-risk cases, which display less than 50% prolonged survival rate despite intense multimodal treatment. Somehow paradoxically, MYCN also sensitizes neuroblastoma cells to apoptosis, understanding the molecular mechanisms of which might be relevant for the therapy of MYCN amplified neuroblastoma. We recently reported that the apoptosis-sensitive phenotype induced by MYCN is linked to stabilization of p53 and its proapoptotic kinase HIPK2. In MYCN primed neuroblastoma cells, further activation of both HIPK2 and p53 by Nutlin-3 leads to massive apoptosis in vitro and to tumor shrinkage an…