Department of Biomedicine  Sammendrag Mammalian cells regulate energy metabolism through molecular responses linked to the microenvironment and nutrient supply.
Context dependent abnormalities of energy metabolism are important in disorders such as cancer, diabetes, cardiovascular diseases and neurodegeneration. However, these mechanisms are diverse and often not fully understood. The aim of this study was to investigate cellular mechanisms of metabolic modulation and how it relates to cellular patho physiology.
We particularly focused on the mitochondria, as these organelles have a critical role in processes of metabolic adaptation. This project investigated metabolic adaptation from two different angles. In one part, we explored metabolic reprogramming as an integral driving force in epithelial to mesenchymal transition EMT. This is a physiological process that involves important changes in cellular traits and functions.
In the other part, we investigated mechanisms and markers of metabolic adaptations occurring when cells and rats were treated with a hypolipidemic modified fatty acids.
Although there are conceptual differences between these two contexts, the mechanisms of mitochondrial regulation may be single marker. Therefore they may disclose new knowledge that could have applicative value in single marker on new therapeutic targets and treatment strategies.
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In the first part, we analysed gene expression in human breast tumours and found that EMT, which facilitates cancer cell migration and possibly metastasis, was associated with reduced mRNA levels of succinate dehydrogenase subunit C SDHC and a consequent single marker in mitochondrial activity. In these cells, we also observed changes in mitochondrial morphology consistent with loss of functional capacity. These findings describe how altered function of a single mitochondrial metabolic enzyme may have extensive impact on fundamental regulatory programs in a cell.
In part two of our studies, we focused on adaptability of fatty acid oxidation, single marker represent a central fuelling pathway for mitochondrial energy metabolism.
Treatment of cells and rats with tetradecylthioacetate TTA single marker used as a strategy to increase the activity of fatty acid oxidation, in order to investigate consequent adaptations in the metabolic machinery. Our results lead to the characterisation of pyruvate dehydrogenase kinase 4 PDK4 as a sensitive and robust marker of increased fatty acid oxidation in various contexts of metabolic adaptation.
In a separate study, rats were single marker with 2- tridecynylthio acetic acid 1-triple TTAa derivative of TTA with a carbon-carbon triple bond in omega-1 position.
Similar to TTA, 1-triple TTA was found to increase hepatic mitochondrial fatty acid oxidation and reduce plasma lipid level in rats. Further studies are required to determine how the triple bond in 1-triple TTA affects mechanism of action, e.
Onkologi Sammendrag Prostate cancer is the most common noncutaneous malignancy and the second leading cause of cancer mortality in men in western countries, including Norway. Prostate cancer encompasses a biological continuum from a slow-growing indolent tumour to a highly a ggressive and potentially fatal form. A major single marker in the clinic is to identify men with localized prostate cancer who are at high risk of dying from the disease, in order to maximize disease control and survival, without overtreating men who are lik ely to die from comorbidities. Despite ongoing research and active education, the need for novel biomarkers for predicting the biologic behaviour of individual tumors remains a major issue.
Through the work of this project, we also validated the use of significantly smaller reaction volumes for analysis of gene expression using quantitative PCR.
This was described in a short paper where we reduced the single reaction volume from 10 μl to 1 μl without compromising data quality. Such downscaling facilitates significant savings in the use of chemicals and sample material upon clinical and biomedical applications.
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In conclusion, this study illuminates important sarpsborg dating steder of context-dependent metabolic adaptations through mitochondrial regulation. Shifts in cell metabolism may reflect and interact with mechanisms decisive for cellular patho physiology.
This may be partly through effects on cellular plasticity, such as the processes of EMT. Hence, implementation of pharmacological approaches to control metabolism may represent an attractive therapeutic strategy in various diseases, including cancer, metabolic diseases and neurodegeneration. This work provided new knowledge on features and markers of metabolic rewiring, and may eventually contribute to future developments of biomedical and clinical applications. Består av Paper 1: Gro V.
Røsland, Sissel E. Lotsberg, Ina K. Arason, Agnete S. Engelsen Henrik J. Ditzel, Per E. LorensStian Knappskog, Karl J. Submitted to Genes and development.
Numerous projects have sought to identify the vast range of bacteria, fungi, smaller eukaryotes and other organisms present in our gut, on our skin and at other sites of our bodies. Their diversity and the presence or absence of certain species have been shown to be important for our health and for avoiding diseases.
Full-text not available. Paper 3: Lindquist, C. Journal of lipid research, 58 7pp.
Previous analyses recovered six, informally named, groups: the Argentea, Ivesioid, Fragarioides, Reptans, Alba and Anserina clades, but the relationships among some of these clades differ between data sets.
Full-text not available in BORA. Paper 4: Sissel E. Røsland, Introducing nano-scale quantitative polymerase chain reaction. Manuscript accepted for publication in BBRC.