Biomedical subjects

Eeva Rissanen

Publications and source records attributed to Eeva Rissanen.

5 recordsLinked to original sources

PubMed2006

Oxygen availability regulates metabolism and gene expression in trout hepatocyte cultures.

We studied the metabolic rate, cellular energetic state, hypoxia-inducible factor-1 (HIF-1) activation, and expression of enzymes involved in energy metabolism using rainbow trout (Oncorhynchus mykiss) hepatocytes over the oxygen range from 21 to 1 kPa. Oxygen dependence of these factors was assessed by gradually reducing oxygen supply to cells from 21 kPa to 10, 5, 2, and 1 kPa. Moreover, time course experiments for up to 20 h at oxygen tensions of 1 and 2 kPa were carried out. Reduction of oxygen from 21 kPa to 10, 5, 2, and 1 kPa decreased metabolic rate of the cells by 14, 24, 37, and 46%, respectively. This response was instantaneous and fully reversible upon reoxygenation. Cellular ATP content and the expression of all mRNAs studied decreased when oxygen was reduced from 21 to 5 and 2 kPa. The lowest ATP levels, approximately 43% of the initial value, were measured at 5 kPa of oxygen, whereas the reduction in mRNA amounts was most pronounced at 2 kPa. At 1 kPa oxygen tension, both ATP content and mRNA amounts returned to normoxic (21 kPa) levels with a concomitant activation of HIF-1, indicating reorganization of energy metabolism in adaptation of cells to low oxygen supply. These results show that oxygen has a direct regulatory effect on metabolism of trout hepatocyte cultures, supporting the view that oxygen has a profound role in metabolic regulation in cells.

Actins↗

PubMed2006

Temperature regulates hypoxia-inducible factor-1 (HIF-1) in a poikilothermic vertebrate, crucian carp (Carassius carassius).

Hypoxia-inducible transcription factor-1 (HIF-1) is a master regulator of hypoxia-induced gene responses. To find out whether HIF-1 function is involved in gene expression changes associated with temperature acclimation as well as in hypoxia adaptation in poikilotherms, we studied HIF-1 DNA binding activity and HIF-1alpha expression in normoxia and during hypoxia (0.7 mg l(-1) O2) in crucian carp at temperatures of 26, 18 and 8 degrees C. Temperature had a marked influence on HIF-1 in normoxia. Although HIF-1alpha mRNA levels remained unaltered, cold acclimation (8 degrees C) increased HIF-1alpha protein amounts in the liver, gills and heart and HIF-1 DNA binding activity in the heart, gills and kidney of crucian carp by two- to threefold compared to warm acclimated fish (26 degrees C). In the heart and kidney HIF-1 activity was already significantly increased in the 18 degrees C acclimated fish. Temperature also affected hypoxic regulation of HIF-1. Although hypoxia initially increased amounts of HIF-1alpha protein in all studied tissues at every temperature, except for liver at 18 degrees C, HIF-1 activity increased only in the heart of 8 degrees C acclimated and in the gills of 18 degrees C acclimated fish. At 8 degrees C HIF-1alpha mRNA levels increased transiently in the gills after 6 h of hypoxia and in the kidney after 48 h of hypoxia. In the gills at 26 degrees C HIF-1alpha mRNA levels increased after 6 h of hypoxia and remained above normoxic levels for up to 48 h of hypoxia. These results show that HIF-1 is involved in controlling gene responses to both oxygen and temperature in crucian carp. No overall transcriptional control mechanism has been described for low temperature acclimation in poikilotherms, but the present results suggest that HIF-1 could have a role in such regulation. Moreover, this study highlights interaction of the two prime factors defining metabolism, temperature and oxygen, in the transcriptional control of metabolic homeostasis in animals.

Acclimatization↗

PubMed2005

HIF-1alpha and iNOS levels in crucian carp gills during hypoxia-induced transformation.

Hypoxia inducible factor 1 alpha (HIF-1alpha) initiates expression of a wide variety of genes, some of which are involved in apoptosis and cell cycle arrest. We have previously shown that crucian carp increases its respiratory surface area 7.5-fold in response to hypoxia. This change is due to apoptosis and cell cycle arrest in specific parts of its gills. Here we have characterized crucian carp HIF-1alpha, and measured mRNA, protein and DNA binding levels during hypoxia exposure in crucian carp gills. We have also measured an HIF-1alpha-induced gene, the inducible nitric oxide synthase (iNOS), which has the ability to initiate apoptosis and cell cycle arrest. Crucian carp HIF-1alpha was found to have all critical domains known to be important for function. Comparison of the peptide sequence with other species indicated high similarity with other cyprinid fish, but a pronounced variation compared to the salmonid, rainbow trout. Further, we found HIF-1alpha protein to be stabilized during hypoxia. Further, HIF-1alpha was often present in normoxia, and showed marked individual weight-dependent variation. We found no alteration of iNOS mRNA levels during hypoxia exposure. These findings suggest HIF-1alpha involvement in hypoxia-induced change of respiratory surface area in crucian carp gills. However, its activity does not seem to be mediated through iNOS.

Amino Acid Sequence↗

PubMed2005

Visual function in epilepsy patients treated with initial valproate monotherapy.

PURPOSE: To investigate whether initial valproate (VPA) monotherapy for the treatment of epilepsy causes visual field defects and visual dysfunction. METHODS: In a cross-sectional study, visual fields were examined with the kinetic Goldmann and automated Humphrey perimeters, contrast sensitivity function with the Pelli-Robson letter chart and colour vision with the Standard Pseudoisochromatic Plates Part 2 (SPP 2) and Farnsworth-Munsell 100 Hue test (FM 100) in eighteen epilepsy patients (aged 18--50 years, 30.2.+/-10 years, mean+/-S.D.) treated with initial valproate monotherapy for 2--20 years (8.4+/-5.1 years). RESULTS: None had vigabatrin-type, concentric visual field defect with the kinetic Goldmann or automated Humphrey perimetries. In the Humphrey perimetry, the mean deviation for the group was within normal limits varying from -2.53 to 0.59 dB (-0.74+/-0.80 dB) in the right eye and from -2.66 to 0.67 dB (-0.78+/-0.82 dB) in the left eye. In the FM 100 test, acquired colour vision deficiency was found in two out of 18 patients (11%, 95% CI: 0--25%). However, the mean total error score was lower in the patient group than in the control group. All patients had normal contrast sensitivity function. CONCLUSIONS: The use of VPA in the treatment of epilepsy is not associated with visual field defects similar to vigabatrin, but may induce abnormalities in colour vision.

Adult↗

PubMed2003

Dehydroabietic acid, a major component of wood industry effluents, interferes with cellular energetics in rainbow trout hepatocytes.

We studied the effects of dehydroabietic acid (DHAA), a major toxic resin acid in wood industry effluents, on cellular energetics in rainbow trout (Oncorhynchus mykiss) hepatocytes. In addition, the role of DHAA-induced change in intracellular Ca(2+) in the energetic responses of the cells was evaluated. At sublytic concentrations, DHAA caused a reduction in cellular ATP content and a concomitant enhancement of glycolytic activity of the cells in a dose-dependent manner. No further decrease of cellular ATP content occurred after 60 min of DHAA-treatment indicating establishment of new energetic steady state in cells. DHAA also caused a rapid dose-dependent increase in oxygen consumption and in cellular heat production of the hepatocytes. The effect of DHAA on ATP content and glycolytic activity was independent from Ca(2+), whereas, changes in oxygen consumption and heat production were Ca(2+) -dependent. These results show that DHAA induces energetic imbalance in rainbow trout hepatocytes, which is apparently not due to direct interference of DHAA with ATP production nor does it seem to be caused by an indirect effect of elevated intracellular Ca(2+) concentration on mitochondrial energetics. Therefore, the ATP depletion is likely due to increased cellular ATP consumption caused by amphiphilic action of DHAA on the cell membrane.

Abietanes↗