scholarly journals Cavefish cope with environmental hypoxia by developing more erythrocytes and overexpression of hypoxia inducible genes

eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Corine M van der Weele ◽  
William R Jeffery
Keyword(s):  
Normal Development ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Tolerance ◽  
Astyanax Mexicanus ◽  
Hypoxia Inducible Factor 1 ◽  
Primitive Hematopoiesis ◽  
Cave Environment ◽  
Surface Dwelling ◽  
Inducible Genes ◽  
Lateral Mesoderm

Dark caves lacking primary productivity can expose subterranean animals to hypoxia. We used the surface-dwelling (surface fish) and cave-dwelling (cavefish) morphs of Astyanax mexicanus as a model for understanding the mechanisms of hypoxia tolerance in the cave environment. Primitive hematopoiesis, which is restricted to the posterior lateral mesoderm in other teleosts, also occurs in the anterior lateral mesoderm in Astyanax, potentially pre-adapting surface fish for hypoxic cave colonization. Cavefish have enlarged both hematopoietic domains and develop more erythrocytes than surface fish, which are required for normal development in both morphs. Laboratory induced hypoxia suppresses growth in surface fish but not in cavefish. Both morphs respond to hypoxia by overexpressing hypoxia-inducible factor 1 (hif1) pathway genes, and some hif1 genes are constitutively upregulated in normoxic cavefish to similar levels as in hypoxic surface fish. We conclude that cavefish cope with hypoxia by increasing erythrocyte development and constitutive hif1 gene overexpression.

scholarly journals Multi-Omic Meta-Analysis of Transcriptomes and the Bibliome Uncovers Novel Hypoxia-Inducible Genes

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 582
Author(s):  
Yoko Ono ◽  
Hidemasa Bono
Keyword(s):  
Meta Analysis ◽  
Hypoxia Inducible Factor ◽  
Data Driven ◽  
Similarity Coefficients ◽  
Hypoxia Inducible Factor 1 ◽  
Response System ◽  
Inducible Genes ◽  
The Relationship ◽  
G Protein Coupled ◽  
Sufficient Oxygen

Hypoxia is a condition in which cells, tissues, or organisms are deprived of sufficient oxygen supply. Aerobic organisms have a hypoxic response system, represented by hypoxia-inducible factor 1-α (HIF1A), to adapt to this condition. Due to publication bias, there has been little focus on genes other than well-known signature hypoxia-inducible genes. Therefore, in this study, we performed a meta-analysis to identify novel hypoxia-inducible genes. We searched publicly available transcriptome databases to obtain hypoxia-related experimental data, retrieved the metadata, and manually curated it. We selected the genes that are differentially expressed by hypoxic stimulation, and evaluated their relevance in hypoxia by performing enrichment analyses. Next, we performed a bibliometric analysis using gene2pubmed data to examine genes that have not been well studied in relation to hypoxia. Gene2pubmed data provides information about the relationship between genes and publications. We calculated and evaluated the number of reports and similarity coefficients of each gene to HIF1A, which is a representative gene in hypoxia studies. In this data-driven study, we report that several genes that were not known to be associated with hypoxia, including the G protein-coupled receptor 146 gene, are upregulated by hypoxic stimulation.

scholarly journals Hypoxia-inducible factor-1 mediates adaptive developmental plasticity of hypoxia tolerance in zebrafish, Danio rerio

2014 ◽  
Vol 281 (1786) ◽  
pp. 20140637 ◽  
Author(s):  
Cayleih E. Robertson ◽  
Patricia A. Wright ◽  
Louise Köblitz ◽  
Nicholas J. Bernier
Keyword(s):  
Danio Rerio ◽  
Cellular Response ◽  
Developmental Plasticity ◽  
Developmental Stages ◽  
Critical Role ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Tolerance ◽  
Anthropogenic Factors ◽  
Critical Window ◽  
Hypoxia Inducible Factor 1

In recent years, natural and anthropogenic factors have increased aquatic hypoxia the world over. In most organisms, the cellular response to hypoxia is mediated by the master regulator hypoxia-inducible factor-1 (HIF-1). HIF-1 also plays a critical role in the normal development of the cardiovascular system of vertebrates. We tested the hypothesis that hypoxia exposures which resulted in HIF-1 induction during embryogenesis would be associated with enhanced hypoxia tolerance in subsequent developmental stages. We exposed zebrafish ( Danio rerio ) embryos to just 4 h of severe hypoxia or total anoxia at 18, 24 and 36 h post-fertilization (hpf). Of these, exposure to hypoxia at 24 and 36 hpf as well as anoxia at 36 hpf activated the HIF-1 cellular pathway. Zebrafish embryos that acutely upregulated the HIF-1 pathway had an increased hypoxia tolerance as larvae. The critical window for hypoxia sensitivity and HIF-1 signalling was 24 hpf. Adult male fish had a lower critical oxygen tension ( P crit ) compared with females. Early induction of HIF-1 correlated directly with an increased proportion of males in the population. We conclude that mounting a HIF-1 response during embryogenesis is associated with long-term impacts on the phenotype of later stages which could influence both individual hypoxia tolerance and population dynamics.

A new HIF-1 alpha variant induced by zinc ion suppresses HIF-1-mediated hypoxic responses

2001 ◽  
Vol 114 (22) ◽  
pp. 4051-4061
Author(s):  
Yang-Sook Chun ◽  
Eunjoo Choi ◽  
Eun-Jin Yeo ◽  
Jong Ho Lee ◽  
Myung-Suk Kim ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Consensus Sequence ◽  
Hypoxia Inducible Factor ◽  
Zinc Ion ◽  
Dominant Negative ◽  
Hypoxia Inducible Factor 1 ◽  
Aryl Hydrocarbon ◽  
Hypoxic Conditions ◽  
Alpha Variant ◽  
Inducible Genes

The expressions of hypoxia-inducible genes are upregulated by hypoxia-inducible factor 1 (HIF-1), which is a heterodimer of HIF-1α and HIF-1β/ARNT (aryl hydrocarbon receptor nuclear transporter). Under hypoxic conditions, HIF-1α becomes stabilized and both HIF-1α and ARNT are translocated into the nucleus and codimerized, binding to the HIF-1 consensus sequence and transactivating hypoxia-inducible genes. Other than hypoxia, cobalt and nickel, which can substitute for iron in the ferroprotein, induce the stabilization of HIF-1α and the activation of HIF-1. We found previously that, although zinc, another example of a metal substitute for iron, stabilized HIF-1α, it suppressed the formation of HIF-1 by blocking the nuclear translocation of ARNT. Here, we identify a new spliced variant of human HIF-1α that is induced by zinc. The isoform lacks the 12th exon, which produced a frame-shift and gave a shorter form of HIF-1α (557 amino acids), designated HIF-1αZ (HIF-1α induced by Zn). This moiety was found to inhibit HIF-1 activity and reduce mRNA expressions of the hypoxia-inducible genes. It blocked the nuclear translocation of ARNT but not that of endogenous HIF-1α, and was associated with ARNT in the cytosol. These results suggest that HIF-1αZ functions as a dominant-negative isoform of HIF-1 by sequestering ARNT in the cytosol. In addition, the generation of HIF-1αZ seems to be responsible for the inhibitory effects of the zinc ion on HIF-1-mediated hypoxic responses, because the expressed HIF-1αZ behaved in the same manner as zinc in terms of inhibited HIF-1 activity and ARNT translocation.

Linkage of Pteridine Metabolism to Iron Homeostasis

Pteridines ◽  
2004 ◽  
Vol 15 (3) ◽  
pp. 120-125
Author(s):  
Günter Weiss
Keyword(s):  
Iron Homeostasis ◽  
Critical Role ◽  
Hypoxia Inducible Factor ◽  
Central Component ◽  
Regulation Of Transcription ◽  
Binding Affinities ◽  
Hypoxia Inducible Factor 1 ◽  
Proliferation And Differentiation ◽  
Inducible Genes ◽  
Essential Growth

Abstract Iron is an essential growth factor for the proliferation and differentiation of all living cells in being centrally involved in oxygen transport by hemoglobin and myoglobin, in electron transport during mitochondrial respiration as being a part of complex I and II enzymes or in the regulation of transcription via its role as central component of ribonucelotid reductase (1,2). Moroever, iron plays a critical role in macrophage mediated cytotoxicity by contributing to the production of highly toxic hydroxy radical species needed for host defense (3). In addition, radicals formed by the catalytic action of by iron can modulate the binding affinities of several transcription factors to their target promoter region, such as hypoxia inducible factor -1 or nuclear factor-kB, thus affecting transcription of stress inducible genes (4-6).

scholarly journals Cavefish Increase Red Blood Cell Development and Reprogram Metabolism as Adaptations to Environmental Hypoxia

2019 ◽  
Author(s):  
Corine M. van der Weele ◽  
William R. Jeffery
Keyword(s):  
Blood Cell ◽  
Red Blood Cells ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Cell Formation ◽  
Single Species ◽  
Marker Genes ◽  
Astyanax Mexicanus ◽  
Cave Environment ◽  
Lateral Mesoderm

AbstractThe teleost Astyanax mexicanus is a single species with surface dwelling (surface fish) and cave dwelling (cavefish) morphs. Constructive and regressive traits have evolved in cavefish as adaptations for survival in perpetual darkness. In addition to darkness, cavefish must cope with de-oxygenated aquatic environments. Blood cell quantification and expression of hematopoietic marker genes indicated that cavefish have more erythrocytes than surface fish, and that this increase has a developmental basis. In contrast to zebrafish and other teleost embryos, in which erythrocyte formation is restricted to the posterior lateral mesoderm, the anterior as well as the posterior lateral mesoderm is involved in red blood cell formation in Astyanax embryos, and both of these hematopoietic domains are expanded in cavefish embryos. Erythroid development in the anterior mesoderm may be a pre-adaptation for surface fish to successfully colonize hypoxic cave environments. We also show that cavefish are less sensitive to phenylhydrazine-induced erythrocyte ablation than surface fish, suggesting a functional advantage of increased red blood cells. By mimicking a hypoxic cave environment in the laboratory, we further demonstrate that cavefish respond to hypoxia differently than surface fish. Surface fish with fewer red blood cells use overall metabolic depression to counteract hypoxia, whereas cavefish with larger numbers of erythrocytes respond to hypoxia by switching to anaerobic metabolism. These results suggest that cavefish may have adapted to hypoxic environments by enhancing the capacity to form erythrocytes and reprogramming metabolism.SummaryAstyanax mexicanus cavefish adapt to life in hypoxic cave environments by evolving the capacity to increase red blood cell numbers during early development and reprogramming metabolism to favor anaerobic processes.

scholarly journals Hypoxia inducible factor-1 α knockout does not impair acute thermal tolerance or heat hardening in zebrafish

2020 ◽  
Vol 16 (7) ◽  
pp. 20200292
Author(s):  
William Joyce ◽  
Steve F. Perry
Keyword(s):  
High Temperature ◽  
Thermal Tolerance ◽  
Hypoxia Inducible Factor ◽  
Extreme Environments ◽  
Hypoxia Tolerance ◽  
Similar Degree ◽  
Wild Type ◽  
Double Knockout ◽  
Hypoxia Inducible Factor 1 ◽  
Heat Hardening

The rapid increase in critical thermal maximum (CT max ) in fish (or other animals) previously exposed to critically high temperature is termed ‘heat hardening’, which likely represents a key strategy to cope with increasingly extreme environments. The physiological mechanisms that determine acute thermal tolerance, and the underlying pathways facilitating heat hardening, remain debated. It has been posited, however, that exposure to high temperature is associated with tissue hypoxia and may be associated with the increased expression of hypoxia-inducible factor-1 (Hif-1). We studied acute thermal tolerance in zebrafish ( Danio rerio ) lacking functional Hif-1 α paralogs (Hif-1aa and Hif-1ab double knockout; Hif-1 α −/− ), which are known to exhibit markedly reduced hypoxia tolerance. We hypothesized that Hif-1 α −/− zebrafish would suffer reduced acute thermal tolerance relative to wild type and that the heat hardening ability would be lost. However, on the contrary, we observed that Hif-1 α −/− and wild-type fish did not differ in CT max , and both genotypes exhibited heat hardening of a similar degree when CT max was re-tested 48 h later. Despite exhibiting impaired hypoxia tolerance, Hif-1 α −/− zebrafish display unaltered thermal tolerance, suggesting that these traits are not necessarily functionally associated. Hif-1 α is accordingly not required for short-term acclimation in the form of heat hardening.

scholarly journals Specific cyprinid HIF isoforms contribute to cellular mitochondrial regulation

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jing Chen ◽  
Lihong Guan ◽  
Ming Zou ◽  
Shunping He ◽  
Dapeng Li ◽  
...  
Keyword(s):  
Cellular Response ◽  
Genome Duplication ◽  
Citrate Synthase ◽  
Tricarboxylic Acid Cycle ◽  
Hypoxia Inducible Factor ◽  
Cyprinid Fish ◽  
Hypoxia Tolerance ◽  
Mitochondrial Mass ◽  
Mitochondrial Regulation ◽  
Hypoxia Inducible Factor 1

Abstract Hypoxia-inducible factor 1 (HIF-1) functions as a master regulator of the cellular response to hypoxic stress. Two HIF-1α paralogs, HIF-1αA and HIF-1αB, were generated in euteleosts by the specific, third round of genome duplication, but one paralog was later lost in most families with the exception of cyprinid fish. How these duplicates function in mitochondrial regulation and whether their preservation contributes to the hypoxia tolerance demonstrated by cyprinid fish in freshwater environments is not clear. Here we demonstrated the divergent function of these two zebrafish Hif-1a paralogs through cellular approaches. The results showed that Hif-1aa played a role in tricarboxylic acid cycle by increasing the expression of Citrate synthase and the activity of mitochondrial complex II, and it also enhanced mitochondrial membrane potential and ROS production by reducing free Ca2+ in the cytosol. Hif-1ab promoted intracellular ATP content by up-regulating the activity of mitochondrial complexes I, III and IV and the expression of related genes. Furthermore, both the two zebrafish Hif-1a paralogs promoted mitochondrial mass and the expression level of mtDNA, contributing to mitochondrial biogenesis. Our study reveals the divergent functions of Hif-1aa and Hif-1ab in cellular mitochondrial regulation.

scholarly journals The Regulation of Hypoxic Genes by Calcium Involves c-Jun/AP-1, Which Cooperates with Hypoxia-Inducible Factor 1 in Response to Hypoxia

2002 ◽  
Vol 22 (6) ◽  
pp. 1734-1741 ◽  
Author(s):  
Konstantin Salnikow ◽  
Thomas Kluz ◽  
Max Costa ◽  
David Piquemal ◽  
Zoya N. Demidenko ◽  
...  
Keyword(s):  
Gene Expression ◽  
Kinase Inhibitor ◽  
Regulation Of Gene Expression ◽  
Hypoxia Inducible Factor ◽  
Dominant Negative ◽  
Activator Protein 1 ◽  
Hypoxia Inducible Factor 1 ◽  
Intracellular Ca ◽  
Inducible Genes ◽  
Endothelial Growth Factor

ABSTRACT Hypoxia causes the accumulation of the transcription factor hypoxia-inducible factor 1 (HIF-1), culminating in the expression of hypoxia-inducible genes such as those for vascular endothelial growth factor (VEGF) and NDRG-1/Cap43. Previously, we have demonstrated that intracellular calcium (Ca2+) is required for the expression of hypoxia-inducible genes. Here we found that, unlike with hypoxia or hypoxia-mimicking conditions, the elevation of intracellular Ca2+ neither induced the HIF-1α protein nor stimulated HIF-1-dependent transcription. Furthermore, the elevation of intracellular Ca2+ induced NDRG-1/Cap43 mRNA in HIF-1α-deficient cells. It also increased levels of c-Jun protein, causing its phosphorylation. The protein kinase inhibitor K252a abolished c-Jun induction and activator protein 1 (AP-1)-dependent reporter expression caused by Ca2+ ionophore or hypoxia. K252a also significantly decreased hypoxia-induced VEGF and NDRG-1/Cap43 gene expression in both human and mouse cells. Using a set of deletion VEGF-Luc promoter constructs, we found that both HIF-1 and two AP-1 sites contribute to hypoxia-mediated induction of transcription. In contrast, only AP-1 sites contributed to Ca2+-mediated VEGF-Luc induction. A dominant-negative AP-1 prevented Ca2+-dependent transcription and partially impaired hypoxia-mediated transcription. In addition, dominant-negative AP-1 diminished the expression of the NDRG-1/Cap43 gene following hypoxia. We conclude that during hypoxia, an increase in intracellular Ca2+ activates a HIF-1-independent signaling pathway that involves AP-1-dependent transcription. Cooperation between the HIF-1 and AP-1 pathways allows fine regulation of gene expression during hypoxia.

scholarly journals Aquatic surface respiration improves survival during hypoxia in zebrafish ( Danio rerio ) lacking hypoxia-inducible factor 1-α

2022 ◽  
Vol 289 (1966) ◽  
Author(s):  
Milica Mandic ◽  
Kaitlyn Flear ◽  
Pearl Qiu ◽  
Yihang K. Pan ◽  
Steve F. Perry ◽  
...  
Keyword(s):  
Danio Rerio ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Tolerance ◽  
Wild Type ◽  
Survival Times ◽  
Aquatic Surface Respiration ◽  
Negative Effects ◽  
Hypoxia Inducible Factor 1 ◽  
Impact On Survival ◽  
The Impact

Hypoxia-inducible factor 1-α (Hif-1α), an important transcription factor regulating cellular responses to reductions in O 2 , previously was shown to improve hypoxia tolerance in zebrafish ( Danio rerio ). Here, we examined the contribution of Hif-1α to hypoxic survival, focusing on the benefit of aquatic surface respiration (ASR). Wild-type and Hif-1α knockout lines of adult zebrafish were exposed to two levels (moderate or severe) of intermittent hypoxia. Survival was significantly compromised in Hif-1α knockout zebrafish prevented from accessing the surface during severe (16 mmHg) but not moderate (23 mmHg) hypoxia. When allowed access to the surface in severe hypoxia, survival times did not differ between wild-type and Hif-1α knockouts. Performing ASR mitigated the negative effects of the loss of Hif-1α with the knockouts initiating ASR at a higher P O 2 threshold and performing ASR for longer than wild-types. The loss of Hif-1α had little impact on survival in fish between 1 and 5 days post-fertilization, but as the larvae aged, their reliance on Hif-1α increased. Similar to adult fish, ASR compensated for the loss of Hif-1α on survival. Together, these results demonstrate that age, hypoxia severity and, in particular, the ability to perform ASR significantly modulate the impact of Hif-1α on survival in hypoxic zebrafish.

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