Metabolic adaptations to environmental changes in Caenorhabditis elegans

Paul, Rüdiger J.; Gohla, Jan; Föll, Roman; Schneckenburger, Herbert

doi:10.1016/s0305-0491(00)00284-4

Cited by 16 publications

(8 citation statements)

References 25 publications

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“…Shifting from oxidative phosphorylation to the O 2 -independent glycolytic pathway is the most ancient cellular response to hypoxia, occurring even in Caenorhabditis elegans (77). Interestingly, HIF-1␣ is conserved from C. elegans to humans and HIF-2␣ only exists in more complicated vertebrates such as chicken, quail, and mammals (24,28,47).…”

Section: Discussionmentioning

confidence: 99%

Differential Roles of Hypoxia-Inducible Factor 1α (HIF-1α) and HIF-2α in Hypoxic Gene Regulation

Wang

Chodosh

et al. 2003

Molecular and Cellular Biology

1,240

1,078

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Transcriptional responses to hypoxia are primarily mediated by hypoxia-inducible factor (HIF), a heterodimer of HIF-␣ and the aryl hydrocarbon receptor nuclear translocator subunits. The HIF-1␣ and HIF-2␣ subunits are structurally similar in their DNA binding and dimerization domains but differ in their transactivation domains, implying they may have unique target genes. Previous studies using Hif-1␣ ؊/؊ embryonic stem and mouse embryonic fibroblast cells show that loss of HIF-1␣ eliminates all oxygen-regulated transcriptional responses analyzed, suggesting that HIF-2␣ is dispensable for hypoxic gene regulation. In contrast, HIF-2␣ has been shown to regulate some hypoxia-inducible genes in transient transfection assays and during embryonic development in the lung and other tissues. To address this discrepancy, and to identify specific HIF-2␣ target genes, we used DNA microarray analysis to evaluate hypoxic gene induction in cells expressing HIF-2␣ but not HIF-1␣. In addition, we engineered HEK293 cells to express stabilized forms of HIF-1␣ or HIF-2␣ via a tetracycline-regulated promoter. In this first comparative study of HIF-1␣ and HIF-2␣ target genes, we demonstrate that HIF-2␣ does regulate a variety of broadly expressed hypoxia-inducible genes, suggesting that its function is not restricted, as initially thought, to endothelial cell-specific gene expression. Importantly, HIF-1␣ (and not HIF-2␣) stimulates glycolytic gene expression in both types of cells, clearly showing for the first time that HIF-1␣ and HIF-2␣ have unique targets.Oxygen (O 2 ), the final electron acceptor during oxidative phosphorylation, is absolutely required for invertebrate and vertebrate life. The immediate response to O 2 deprivation (hypoxia) is a defense phase, which suppresses ATP consumption by arresting protein translation and ion channel activity, two major ATP sinks during normoxia. During a rescue phase, in spite of a general reduction in RNA synthesis, transcription of some genes increases dramatically under low O 2 (21, 34). These hypoxia-responsive genes are involved in glucose transport, glycolysis, erythropoiesis, angiogenesis, vasodilation, and respiratory rate, and together they function to minimize the effects caused by low O 2 at cellular, tissue and systemic levels (93, 106).The activation of many O 2 -regulated genes is mediated by hypoxia-inducible factor (HIF), a heterodimer consisting of HIF-1␣ and HIF-1␤ (also called the aryl hydrocarbon receptor nuclear translocator [ARNT]) in most cells (52,104,105). Both HIF-1␣ and ARNT belong to the basic helix-loop-helix (bHLH)-Per-Arnt-Sim (PAS) family of transcription factors, which share several conserved structural domains, including a bHLH region for DNA binding and two PAS domains for target gene specificity and dimerization (102). Although ARNT is absolutely required for HIF activity (63, 110), HIF function is primarily regulated by HIF-1␣ protein stability (37,46,84). Under normoxia, HIF-1␣ is ubiquitinated through interaction with the von Hippel-Lindau tumor suppr...

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Section: Discussionmentioning

confidence: 99%

Differential Roles of Hypoxia-Inducible Factor 1α (HIF-1α) and HIF-2α in Hypoxic Gene Regulation

Wang

Chodosh

et al. 2003

Molecular and Cellular Biology

1,240

1,078

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“…Zebrafish, in response to cold temperature, increase specific antioxidant enzymes such as superoxide dismutase (SOD)-1 and SOD-2 (Malek et al 2004), and carp also show a specific gene expression profile in response to cold temperature that is reminiscent of those changes seen in calorically restricted mice (Gracey et al 2004;Han and Hickey 2005;Lee et al 1999Lee et al , 2000. C. elegans also displays a specific physiological change in response to cold temperatures (Madi et al 2003;Paul et al 2000), and it has even been noted that cold temperature is a type of mild stress, which suggests a possible hormetic effect. Wong et al have shown that clk-1 mutants are insensitive to temperature changes during embryogenesis, which demonstrates that developmental adjustments to changing temperatures is an active process requiring genes such as clk-1 (Wong et al 1995).…”

Section: Introductionmentioning

confidence: 99%

Evidence for only two independent pathways for decreasing senescence in Caenorhabditis elegans

Yen

Mobbs

2009

AGE

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Cold temperature, dietary restriction, reduced insulin/insulin-like growth factor signaling, and mutations in mitochondrial genes have all been shown to extend the lifespan of Caenorhabditis elegans (Kenyon et al., Nature 366:461-464, 1993; Klass, Mech Ageing Dev 6:413-429, 1977; Lakowski and Hekimi, Science 272:1010-1013. Additionally, all of them extend the lifespan of mice (Bluher et al., Science 299:572-574, 2003; Conti et al., Science 314:825-828, 2006; Holzenberger et al., Nature 421:182-187, 2003; Liu et al., Genes Dev 19:2424-2434 Weindruch and Walford, Science 215:1415-1418, 1982. The mechanism by which these treatments extend lifespan is currently unknown, but our study uses an epistatic approach to show that these four manipulations are mainly additive in terms of lifespan. Classical interpretation of this data suggests that these manipulations are independent of each other. However, using a Gompertz mortality rate analysis, the maximum mortality rate doubling time can be achieved through the use of only dietary restriction and cold temperature, suggesting that the mechanisms by which cold temperature and caloric restriction extend lifespan are the only independent mechanisms.

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“…This phenotype could be a direct result of decreased GAPDH activity. In wild-type adult C. elegans, there is a correlation between the anoxia-induced arrest of motility with constant levels of protein-bound NADH and an increase in free NADH (Paul et al 2000). Thus, it would be of interest to determine and compare the levels of free NADH and protein-bound NADH in the daf-2(e1370), wild-type, gpd-2(RNAi), and daf-2(e1370);gpd-2(RNAi) animals exposed to anoxia.…”

mentioning

confidence: 99%

Glyceraldehyde-3-Phosphate Dehydrogenase Mediates Anoxia Response and Survival in Caenorhabditis elegans

2006

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Oxygen deprivation has a role in the pathology of many human diseases. Thus it is of interest in understanding the genetic and cellular responses to hypoxia or anoxia in oxygen-deprivation-tolerant organisms such as Caenorhabditis elegans. In C. elegans the DAF-2/DAF-16 pathway, an IGF-1/insulin-like signaling pathway, is involved with dauer formation, longevity, and stress resistance. In this report we compared the response of wild-type and daf-2(e1370) animals to anoxia. Unlike wild-type animals, the daf-2(e1370) animals have an enhanced anoxia-survival phenotype in that they survive long-term anoxia and hightemperature anoxia, do not accumulate significant tissue damage in either of these conditions, and are motile after 24 hr of anoxia. RNA interference was used to screen DAF-16-regulated genes that suppress the daf-2(e1370)-enhanced anoxia-survival phenotype. We identified gpd-2 and gpd-3, two nearly identical genes in an operon that encode the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase. We found that not only is the daf-2(e1370)-enhanced anoxia phenotype dependent upon gpd-2 and gpd-3, but also the motility of animals exposed to brief periods of anoxia is prematurely arrested in gpd-2/3(RNAi) and daf-2(e1370);gpd-2/3(RNAi) animals. These data suggest that gpd-2 and gpd-3 may serve a protective role in tissue exposed to oxygen deprivation.

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Metabolic adaptations to environmental changes in Caenorhabditis elegans

Cited by 16 publications

References 25 publications

Differential Roles of Hypoxia-Inducible Factor 1α (HIF-1α) and HIF-2α in Hypoxic Gene Regulation

Differential Roles of Hypoxia-Inducible Factor 1α (HIF-1α) and HIF-2α in Hypoxic Gene Regulation

Evidence for only two independent pathways for decreasing senescence in Caenorhabditis elegans

Glyceraldehyde-3-Phosphate Dehydrogenase Mediates Anoxia Response and Survival in Caenorhabditis elegans

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