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Transcriptome analysis of the response to chronic constant hypoxia in zebrafish hearts.

Marques IJ, Leito JT, Spaink HP, Testerink J, Jaspers RT, Witte F, van den Berg S, Bagowski CP - J. Comp. Physiol. B, Biochem. Syst. Environ. Physiol. (2007)

Bottom Line: We describe here that chronic constant hypoxia (CCH) leads to a smaller ventricular outflow tract, reduced lacunae within the central ventricular cavity and around the trabeculae and an increase in the number of cardiac myocyte nuclei per area in the hearts of two teleost species, zebrafish (Danio rerio) and cichlids (Haplochromis piceatus).We have analyzed over 15,000 different transcripts and found 376 differentially regulated genes, of which 260 genes showed increased and 116 genes decreased expression levels.We have identified here many novel genes involved in the response to CCH in the heart, which may have potential clinical implications in the future.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrative Zoology, Institute of Biology, University of Leiden, Wassenaarseweg 64, 2333 AL, Leiden, The Netherlands.

ABSTRACT
Insufficient blood supply during acute infarction and chronic ischemia leads to tissue hypoxia which can significantly alter gene expression patterns in the heart. In contrast to most mammals, some teleost fishes are able to adapt to extremely low oxygen levels. We describe here that chronic constant hypoxia (CCH) leads to a smaller ventricular outflow tract, reduced lacunae within the central ventricular cavity and around the trabeculae and an increase in the number of cardiac myocyte nuclei per area in the hearts of two teleost species, zebrafish (Danio rerio) and cichlids (Haplochromis piceatus). In order to identify the molecular basis for the adaptations to CCH, we profiled the gene expression changes in the hearts of adult zebrafish. We have analyzed over 15,000 different transcripts and found 376 differentially regulated genes, of which 260 genes showed increased and 116 genes decreased expression levels. Two notch receptors (notch-2 and notch-3) as well as regulatory genes linked to cell proliferation were transcriptionally upregulated in hypoxic hearts. We observed a simultaneous increase in expression of IGF-2 and IGFbp1 and upregulation of several genes important for the protection against reactive oxygen species (ROS). We have identified here many novel genes involved in the response to CCH in the heart, which may have potential clinical implications in the future.

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Survival of zebrafish embryos after immediate exposure to hypoxia. Zebrafish were immediately exposed to hypoxia (15 Torr; 0.8 mg/ml; 10% air saturated water). Results are derived from three independent experiments with n = 30 in each experiment (adding to a total of 90 fish tested). After 24, 48 and 72 h, dead and alive fish were counted. Shown here is the percentage of dead fish at the respective time points and the standard deviation. At 24 h 53.3%(±4.4) of fish were dead, at 48 hours 85.3% (±5.1) and at 72 hours 100% (±0). Control groups (n = 30), which were in parallel exposed to normoxic conditions showed no mortality (not shown). None of the zebrafish survived the immediate exposure to an O2 concentration of 0.8 mg/l (10% air saturation) over the 3-day period. In contrast, fishes gradually exposed to hypoxia showed no induced mortality for even the 25 day time periods used in our experiments
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Fig1: Survival of zebrafish embryos after immediate exposure to hypoxia. Zebrafish were immediately exposed to hypoxia (15 Torr; 0.8 mg/ml; 10% air saturated water). Results are derived from three independent experiments with n = 30 in each experiment (adding to a total of 90 fish tested). After 24, 48 and 72 h, dead and alive fish were counted. Shown here is the percentage of dead fish at the respective time points and the standard deviation. At 24 h 53.3%(±4.4) of fish were dead, at 48 hours 85.3% (±5.1) and at 72 hours 100% (±0). Control groups (n = 30), which were in parallel exposed to normoxic conditions showed no mortality (not shown). None of the zebrafish survived the immediate exposure to an O2 concentration of 0.8 mg/l (10% air saturation) over the 3-day period. In contrast, fishes gradually exposed to hypoxia showed no induced mortality for even the 25 day time periods used in our experiments

Mentions: We describe here the survival rates of adult zebrafish upon immediate and gradual exposure to different pO2 concentrations. Immediate exposure to pO2 of 15 Torr (O2 concentration of 0.8 mg/l or 10% air saturated water) was lethal for the adult zebrafish and none survived for longer than 72 h (Fig. 1). If lowered gradually (see experimental procedures for regimen in Sect. “Hypoxia treatment”) zebrafish were able to grow and gain weight at O2 levels of 10% air saturation. The zebrafish were able to survive for longer than 6 months and no mortality was observed, demonstrating that they can well adapt to these conditions (data not shown). For the experiments with zebrafish and cichlids, the pO2 concentration was gradually lowered to 10% air saturation (0.8 mg/l) (see “Material and methods”) and fishes were kept under 10% air saturation for 3 weeks. Control groups were always kept in parallel under normoxic conditions.Fig. 1


Transcriptome analysis of the response to chronic constant hypoxia in zebrafish hearts.

Marques IJ, Leito JT, Spaink HP, Testerink J, Jaspers RT, Witte F, van den Berg S, Bagowski CP - J. Comp. Physiol. B, Biochem. Syst. Environ. Physiol. (2007)

Survival of zebrafish embryos after immediate exposure to hypoxia. Zebrafish were immediately exposed to hypoxia (15 Torr; 0.8 mg/ml; 10% air saturated water). Results are derived from three independent experiments with n = 30 in each experiment (adding to a total of 90 fish tested). After 24, 48 and 72 h, dead and alive fish were counted. Shown here is the percentage of dead fish at the respective time points and the standard deviation. At 24 h 53.3%(±4.4) of fish were dead, at 48 hours 85.3% (±5.1) and at 72 hours 100% (±0). Control groups (n = 30), which were in parallel exposed to normoxic conditions showed no mortality (not shown). None of the zebrafish survived the immediate exposure to an O2 concentration of 0.8 mg/l (10% air saturation) over the 3-day period. In contrast, fishes gradually exposed to hypoxia showed no induced mortality for even the 25 day time periods used in our experiments
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2200676&req=5

Fig1: Survival of zebrafish embryos after immediate exposure to hypoxia. Zebrafish were immediately exposed to hypoxia (15 Torr; 0.8 mg/ml; 10% air saturated water). Results are derived from three independent experiments with n = 30 in each experiment (adding to a total of 90 fish tested). After 24, 48 and 72 h, dead and alive fish were counted. Shown here is the percentage of dead fish at the respective time points and the standard deviation. At 24 h 53.3%(±4.4) of fish were dead, at 48 hours 85.3% (±5.1) and at 72 hours 100% (±0). Control groups (n = 30), which were in parallel exposed to normoxic conditions showed no mortality (not shown). None of the zebrafish survived the immediate exposure to an O2 concentration of 0.8 mg/l (10% air saturation) over the 3-day period. In contrast, fishes gradually exposed to hypoxia showed no induced mortality for even the 25 day time periods used in our experiments
Mentions: We describe here the survival rates of adult zebrafish upon immediate and gradual exposure to different pO2 concentrations. Immediate exposure to pO2 of 15 Torr (O2 concentration of 0.8 mg/l or 10% air saturated water) was lethal for the adult zebrafish and none survived for longer than 72 h (Fig. 1). If lowered gradually (see experimental procedures for regimen in Sect. “Hypoxia treatment”) zebrafish were able to grow and gain weight at O2 levels of 10% air saturation. The zebrafish were able to survive for longer than 6 months and no mortality was observed, demonstrating that they can well adapt to these conditions (data not shown). For the experiments with zebrafish and cichlids, the pO2 concentration was gradually lowered to 10% air saturation (0.8 mg/l) (see “Material and methods”) and fishes were kept under 10% air saturation for 3 weeks. Control groups were always kept in parallel under normoxic conditions.Fig. 1

Bottom Line: We describe here that chronic constant hypoxia (CCH) leads to a smaller ventricular outflow tract, reduced lacunae within the central ventricular cavity and around the trabeculae and an increase in the number of cardiac myocyte nuclei per area in the hearts of two teleost species, zebrafish (Danio rerio) and cichlids (Haplochromis piceatus).We have analyzed over 15,000 different transcripts and found 376 differentially regulated genes, of which 260 genes showed increased and 116 genes decreased expression levels.We have identified here many novel genes involved in the response to CCH in the heart, which may have potential clinical implications in the future.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrative Zoology, Institute of Biology, University of Leiden, Wassenaarseweg 64, 2333 AL, Leiden, The Netherlands.

ABSTRACT
Insufficient blood supply during acute infarction and chronic ischemia leads to tissue hypoxia which can significantly alter gene expression patterns in the heart. In contrast to most mammals, some teleost fishes are able to adapt to extremely low oxygen levels. We describe here that chronic constant hypoxia (CCH) leads to a smaller ventricular outflow tract, reduced lacunae within the central ventricular cavity and around the trabeculae and an increase in the number of cardiac myocyte nuclei per area in the hearts of two teleost species, zebrafish (Danio rerio) and cichlids (Haplochromis piceatus). In order to identify the molecular basis for the adaptations to CCH, we profiled the gene expression changes in the hearts of adult zebrafish. We have analyzed over 15,000 different transcripts and found 376 differentially regulated genes, of which 260 genes showed increased and 116 genes decreased expression levels. Two notch receptors (notch-2 and notch-3) as well as regulatory genes linked to cell proliferation were transcriptionally upregulated in hypoxic hearts. We observed a simultaneous increase in expression of IGF-2 and IGFbp1 and upregulation of several genes important for the protection against reactive oxygen species (ROS). We have identified here many novel genes involved in the response to CCH in the heart, which may have potential clinical implications in the future.

Show MeSH
Related in: MedlinePlus