Biomedical subjects

Lars Folke Olsen

Publications and source records attributed to Lars Folke Olsen.

6 recordsLinked to original sources

PubMed2006

Single cell studies and simulation of cell-cell interactions using oscillating glycolysis in yeast cells.

The observation of oscillations in the concentrations of NADH and other intermediates in glycolysis in dense yeast cell suspensions is generally believed to be the result of synchronization of such oscillations between individual cells. The synchrony is believed to be a property of cell density and the question is: does metabolism in each individual yeast cell continue to oscillate, but out of phase, in the absence of synchronization? Here we have used high-sensitivity fluorescence microscopy to measure NADH in single isolated yeast cells under conditions where we observe oscillations of glycolysis in dense cell suspensions. However, we have not been able to detect intracellular oscillations in NADH in these isolated cells, which cannot synchronize their metabolism with other cells. However, addition of acetaldehyde to a single cell as pulses with a frequency similar to the oscillations in dense cell suspensions will induce oscillations in that cell. Ethanol, another product of glycolysis, which has been proposed as a synchronizing agent of glycolysis in cells, was not able to induce oscillations when added as pulses. The experiments support the notion that the intracellular oscillations are associated with the cell density of the yeast cell suspension and mediated by acetaldehyde and perhaps also other substances.

Acetaldehyde↗

PubMed2005

On-line monitoring of CO2 production in Lactococcus lactis during physiological pH decrease using membrane inlet mass spectrometry with dynamic pH calibration.

Monitoring CO2 production in systems, where pH is changing with time is hampered by the chemical behavior and pH-dependent volatility of this compound. In this article, we present the first method where the concentration and production rate of dissolved CO2 can be monitored directly, continuously, and quantitatively under conditions where pH changes rapidly ( approximately 2 units in 15 min). The method corrects membrane inlet mass spectrometry (MIMS) measurements of CO2 for pH dependency using on-line pH analysis and an experimentally established calibration model. It is valid within the pH range of 3.5 to 7, despite pH-dependent calibration constants that vary in a non-linear fashion with more than a factor of 3 in this interval. The method made it possible to determine the carbon dioxide production during Lactococcus lactis fermentations, where pH drops up to 3 units during the fermentation. The accuracy was approximately 5%. We used the method to investigate the effect of initial extracellular pH on carbon dioxide production during anarobic glucose fermentation by non-growing Lactocoocus lactis and demonstrated that the carbon dioxide production rate increases considerably, when the initial pH was increased from 6 to 6.8.

Calibration↗

PubMed2004

Human myeloperoxidase catalyzes an oscillating peroxidase-oxidase reaction.

We have studied the peroxidase-oxidase reaction catalyzed by human myeloperoxidase in an open system where both substrates-molecular oxygen and NADH-are supplied continuously to the reaction mixture. The reaction shows oscillatory kinetics at pH values around 5, provided that the reaction medium in addition to the enzyme and the substrates also contains an aromatic electron mediator such as melatonin or 4-hydroxybenzoic acid and chloride ions at concentrations >1mM. The experimental findings can be simulated by a detailed model of the reaction. The results are important for our understanding of oxidant production in neutrophils.

Chlorides↗

PubMed2004

Sustained glycolytic oscillations--no need for cyanide.

Using fluorescence spectroscopy we detected long trains of macroscopic oscillations in the glycolytic pathway, in whole cell suspensions of Saccharomyces cerevisiae, without addition of cyanide. Such oscillations may be induced if argon or another inert gas is bubbled through the yeast cell suspension. This supports that the synchronizing agent is a volatile compound secreted by the yeast cells, e.g. CO2 and/or acetaldehyde. Our results show that the rate of acetaldehyde removal is not a crucial parameter to the synchronization of the yeast cells. The sample cell was connected to a membrane inlet mass spectrometer (MIMS) for online determination of extracellular non-polar compounds. Oscillations in the secretion of CO2 were detected using the MIMS.

Acetaldehyde↗

PubMed2004

On the encoding and decoding of calcium signals in hepatocytes.

Many different agonists use calcium as a second messenger. Despite intensive research in intracellular calcium signalling it is an unsolved riddle how the different types of information represented by the different agonists, is encoded using the universal carrier calcium. It is also still not clear how the information encoded is decoded again into the intracellular specific information at the site of enzymes and genes. After the discovery of calcium oscillations, one likely mechanism is that information is encoded in the frequency, amplitude and waveform of the oscillations. This hypothesis has received some experimental support. However, the mechanism of decoding of oscillatory signals is still not known. Here, we study a mechanistic model of calcium oscillations, which is able to reproduce both spiking and bursting calcium oscillations. We use the model to study the decoding of calcium signals on the basis of co-operativity of calcium binding to various proteins. We show that this co-operativity offers a simple way to decode different calcium dynamics into different enzyme activities.

Animals↗

PubMed2003

Mechanism of melatonin-induced oscillations in the peroxidase-oxidase reaction.

Melatonin induces oscillations in the peroxidase-oxidase (PO) reaction catalyzed by horseradish peroxidase. We present here studies of the effect of pH, enzyme concentration, and concentration of melatonin on the oscillation frequency. We also present a mechanistic model to explain the experimentally observed changes in oscillation frequency. Using the data obtained here we are able to predict that oscillations will also occur in the PO reaction catalyzed by myeloperoxidase. Myeloperoxidase is an important protein in activated neutrophils and we provide evidence that the oscillations of NAD(P)H, superoxide and hydrogen peroxide in these cells may involve this enzyme. Thus, our experimental system can be considered a model system for the nonrespiratory oxygen metabolism in activated neutrophils and other similar cells participating in the defence against invading pathogens.

Dose-Response Relationship, Drug↗