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 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.

scholarly journals Myeloid Knockout of HIF-1αDoes Not Markedly Affect Hemorrhage/Resuscitation-Induced Inflammation and Hepatic Injury

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
G. Wetzel ◽  
B. Relja ◽  
A. Klarner ◽  
D. Henrich ◽  
N. Dehne ◽  
...  
Keyword(s):  
Hepatic Injury ◽  
Hypoxia Inducible Factor ◽  
Myeloid Cell ◽  
Vascular Endothelial ◽  
Elevated Plasma ◽  
Wild Type ◽  
Hypoxia Inducible Factor 1 ◽  
Myeloid Cell Line ◽  
Endothelial Growth Factor

Background. Hypoxia-inducible factor-1α(HIF-1α) and NF-κB play important roles in the inflammatory response after hemorrhagic shock and resuscitation (H/R). Here, the role of myeloid HIF-1αin liver hypoxia, injury, and inflammation after H/R with special regard to NF-κB activation was studied.Methods. Mice with a conditional HIF-1αknockout (KO) in myeloid cell-line and wild-type (WT) controls were hemorrhaged for 90 min (30±2 mm Hg) and resuscitated. Controls underwent only surgical procedures.Results. After six hours, H/R enhanced the expression of HIF-1α-induced genes vascular endothelial growth factor (VEGF) and adrenomedullin (ADM). In KO mice, this was not observed. H/R-induced liver injury in HIF-1αKO was comparable to WT. Elevated plasma interleukin-6 (IL-6) levels after H/R were not reduced by HIF-1αKO. Local hepatic hypoxia was not significantly reduced in HIF-1αKO compared to controls after H/R. H/R-induced NF-κB phosphorylation in liver did not significantly differ between WT and KO.Conclusions. Here, deleting HIF-1αin myeloid cells and thereby in Kupffer cells was not protective after H/R. This data indicates that other factors, such as NF-κB, due to its upregulated phosphorylation in WT and KO mice, contrary to HIF-1α, are rather key modulators of inflammation after H/R in our model.

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.

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 Plastic responses of survival and fertility following heat stress in pupal and adult Drosophila virilis

2021 ◽  
Author(s):  
Benjamin Walsh ◽  
Steven Parratt ◽  
Natasha Mannion ◽  
Rhonda Snook ◽  
Amanda Bretman ◽  
...  
Keyword(s):  
Heat Stress ◽  
High Temperature ◽  
Temperature Stress ◽  
High Temperatures ◽  
Male Fertility ◽  
Thermal Tolerance ◽  
Drosophila Virilis ◽  
Life History Stage ◽  
Heat Hardening ◽  
The Impact

The impact of rising global temperatures on survival and reproduction is putting many species at risk of extinction. In particular, it has recently been shown that thermal effects on reproduction, especially limits to male fertility, can underpin species distributions in insects. However, the physiological factors influencing fertility at high temperatures are poorly understood. Key factors that affect somatic thermal tolerance such as hardening, the ability to phenotypically increase thermal tolerance after a mild heat shock, and the differential impact of temperature on different life stages, are largely unexplored for thermal fertility tolerance. Here, we examine the impact of high temperatures on male fertility in the cosmopolitan fruit fly Drosophila virilis. We first determined whether temperature stress at either the pupal or adult life-history stage impacts fertility. We then tested the capacity for heat-hardening to mitigate heat-induced sterility. We found that thermal stress reduces fertility in different ways in pupae and adults. Pupal heat stress delays sexual maturity, whereas males heated as adults can reproduce initially following heat stress, but lose the ability to produce offspring. We also found evidence that while heat-hardening in D. virilis can improve high temperature survival, there is no significant protective impact of this same hardening treatment on fertility. These results suggest that males may be unable to prevent the costs of high temperature stress on fertility through heat-hardening which limits a species’ ability to quickly and effectively reduce fertility loss in the face of short-term high temperature events.

The upstream stimulatory factor-2a inhibits plasminogen activator inhibitor-1 gene expression by binding to a promoter element adjacent to the hypoxia-inducible factor-1 binding site

Blood ◽  
2001 ◽  
Vol 97 (9) ◽  
pp. 2657-2666 ◽  
Author(s):  
Anatoly Samoylenko ◽  
Ulrike Roth ◽  
Kurt Jungermann ◽  
Thomas Kietzmann
Keyword(s):  
Plasminogen Activator ◽  
Hypoxia Inducible Factor ◽  
Plasminogen Activator Inhibitor ◽  
Wild Type ◽  
Upstream Stimulatory Factor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Hypoxia Inducible Factor 1 ◽  
Stimulatory Factor ◽  
Activator Inhibitor ◽  
Pai 1

Abstract Plasminogen activator inhibitor-1 (PAI-1) expression is induced by hypoxia (8% O2) via the PAI-1 promoter region −175/−159 containing a hypoxia response element (HRE-2) binding the hypoxia-inducible factor-1 (HIF-1) and an adjacent response element (HRE-1) binding a so far unknown factor. The aim of the present study was to identify this factor and to investigate its role in the regulation of PAI-1 expression. It was found by supershift assays that the upstream stimulatory factor-2a (USF-2a) bound mainly to the HRE-1 of the PAI-1 promoter and to a lesser extent to HRE-2. Overexpression of USF-2a inhibited PAI-1 messenger RNA and protein expression and activated L-type pyruvate kinase expression in primary rat hepatocytes under normoxia and hypoxia. Luciferase (Luc) gene constructs driven by 766 and 276 base pairs of the 5′-flanking region of the PAI-1 gene were transfected into primary hepatocytes together with expression vectors encoding wild-type USF-2a and a USF-2a mutant lacking DNA binding and dimerization activity (ΔHU2a). Cotransfection of the wild-type USF-2a vector reduced Luc activity by about 8-fold, whereas cotransfection of ΔHU2a did not influence Luc activity. Mutation of the HRE-1 (−175/−168) in the PAI-1 promoter Luc constructs decreased USF-dependent inhibition of Luc activity. Mutation of the HRE-2 (−165/−158) was less effective. Cotransfection of a HIF-1α vector could compete for the binding of USF at HRE-2. These results indicated that the balance between 2 transcriptional factors, HIF-1 and USF-2a, which can bind adjacent HRE sites, appears to be involved in the regulation of PAI-1 expression in many clinical conditions.

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 Endothelin-1 mediates intermittent hypoxia-induced inflammatory vascular remodeling through HIF-1 activation

2016 ◽  
Vol 120 (4) ◽  
pp. 437-443 ◽  
Author(s):  
Emmanuelle Gras ◽  
Elise Belaidi ◽  
Anne Briançon-Marjollet ◽  
Jean-Louis Pépin ◽  
Claire Arnaud ◽  
...  
Keyword(s):  
Vascular Remodeling ◽  
Intermittent Hypoxia ◽  
Hypoxia Inducible Factor ◽  
Intima Media Thickness ◽  
Nuclear Factor Κb ◽  
Endothelin Receptor ◽  
Wild Type ◽  
Endothelin 1 ◽  
Hypoxia Inducible Factor 1 ◽  
Obstructive Sleep

Obstructive sleep apnea (OSA) is a major risk factor for cardiovascular mortality, and apnea-induced intermittent hypoxia (IH) is known to promote various cardiovascular alterations such as vascular remodeling. However, the mechanisms that underlie IH remain incompletely investigated. We previously demonstrated that the hypoxia-inducible factor-1 (HIF-1) and endothelin-1 (ET-1) are involved in arterial hypertension and myocardial susceptibility to infarction induced by IH. Thus the objective of the present study was to investigate whether both ET-1 and HIF-1 were also involved in the vascular inflammatory remodeling induced by IH. Mice partially deficient for the Hif1α gene (HIF-1α+/−) and their wild-type equivalents, as well as C57BL/6J mice, treated or not with bosentan, a dual endothelin receptor antagonist, were exposed to IH or normoxia for 2 wk, 8 h/day. Splenocyte proliferative and secretory capacities, aortic nuclear factor-κB (NF-κB) and HIF-1 activities, and expression of cytokines and intima-media thickness (IMT) were measured. IH induced a systemic and aortic inflammation characterized by an increase in splenocyte proliferative and secretory capacities, aortic NF-κB activity, and cytokine expression in the aortic wall. This was accompanied by an increase in IMT. These modifications were prevented in HIF-1α+/− and bosentan-treated mice. The results of this study suggest that ET-1 is a major contributor to the vascular inflammatory remodeling induced by OSA-related IH, probably through HIF-1-dependent activation of NF-κB.

scholarly journals Hypoxia Associated Proteolytic Processing of OS-9 by the Metalloproteinase Meprinβ

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Barry Lee Martin ◽  
Sabena Michelle Conley ◽  
Regine Simone Harris ◽  
Corshe Devon Stanley ◽  
Jean-Marie Vianney Niyitegeka ◽  
...  
Keyword(s):  
Renal Injury ◽  
Ischemia Reperfusion ◽  
Hypoxia Inducible Factor ◽  
Proteolytic Processing ◽  
Kidney Cells ◽  
Wild Type ◽  
Hypoxia Inducible Factor 1 ◽  
Meprin Metalloproteases ◽  
Carboxyl Terminal

Meprin metalloproteases play a role in the pathology of ischemia/reperfusion- (IR-) induced renal injury. The endoplasmic reticulum-associated protein, osteosarcoma-9 (OS-9), has been shown to interact with the carboxyl-terminal tail of meprinβ. More importantly, OS-9 interacts with the hypoxia inducible factor-1α(HIF-1α) and the prolyl-hydroxylase, proteins which mediate the cell’s response to hypoxia. To determine if OS-9 is a meprin substrate, kidney proteins from meprinαβknockout mice (αβKO) (which lack endogenous meprins) and purified human OS-9 were incubated with activated forms of meprin A and meprin B, and Western blot analysis was used to evaluate proteolytic processing of OS-9. Fragmentation of OS-9 was observed in reactions with meprin B, but not meprin A. To determine whether meprin B cleaves OS-9in vivo, wild-type (WT) and meprinαβKO mice were subjected to IR-induced renal injury. Fragmentation of OS-9 was observed in kidney proteins from WT mice subjected to IR, but not in meprinαβKO counterparts. Transfection of kidney cells (MDCK and HEK293) with meprinβcDNA prevented accumulation of OS-9 following exposure to the hypoxia mimic, CoCl2. These data suggest that meprinβinteraction with OS-9 plays a role in the hypoxia response associated with IR-induced renal injury.

Sign in / Sign up

Export Citation Format

Share Document