HIF-1 is required for heat acclimation in the nematode Caenorhabditis elegans

Author: Treinin, M.; Shliar, J.; Jiang, H.; Powell-Coffman, J.A.; Bromberg, Z.; Horowitz, M.

Description: Chronic exposure to environmental heat improves tolerance via heat acclimation (AC). Our previous data on mammals indicate that reprogramming the expression of genes coding for stress proteins and energy-metabolism enzymes plays a major role. Knowledge of pathways leading to AC is limited. For their identification, we established a Caenorhabditis elegans AC model and tested mutants in which signaling pathways pertinent to acclimatory responses are mutated. AC attained by maintaining adult C. elegans at 25 degrees C for 18 h enhanced heat endurance of wild-type worms subjected to heat stress (35 degrees C) and conferred protection against hypoxia and cadmium. Survival curves demonstrated that both daf-2 (insulin receptor pathway) showing enhanced heat tolerance and daf-16 loss-of-function (a transcription factor mediating DAF-2 signaling) mutants benefit from AC, suggesting that the insulin receptor pathway does not mediate AC. In contrast, the hif-1 (hypoxia inducible factor) loss-of-function strain did not show acclimation, and non-acclimated vhl-1 and egl-9 mutants (overexpressing HIF-1) had greater heat endurance than the wild type. Like mammals, HIF-1 and HSP72 levels increased in the wild-type AC nematodes. HSP72 upregulation in AC hif-1 mutants was also observed; however, it was insufficient to improve heat/stress tolerance, suggesting that HIF-1 upregulation is essential for acclimation, whereas HSP72 upregulation in the absence of HIF-1 is inadequate. We conclude that HIF-1 upregulation is both an evolutionarily conserved and a necessary component of heat acclimation. The known targets of HIF-1 imply that metabolic adaptations are essential for AC-dependent tolerance to heat and heavy metals, in addition to their known role in hypoxic adaptation.

Subject headings: Acclimatization/genetics/physiology; Animals; Cadmium/metabolism; Caenorhabditis elegans/genetics/physiology; Caenorhabditis elegans Proteins/biosynthesis/genetics/physiology; DNA-Binding Proteins/biosynthesis/genetics/physiology; Gene Expression Regulation/physiology; Genes, Helminth/genetics/physiology; Hot Temperature; Hypoxia-Inducible Factor 1; Metals, Heavy/metabolism; Mutation; Nuclear Proteins/biosynthesis/genetics/physiology; Phenotype; Receptor, Insulin/physiology; Signal Transduction/genetics/physiology; Survival Analysis; Transcription Factors; C elegans

Publication year: 2003

Journal or book title: Physiological Genomics

Volume: 14

Issue: 1

Pages: 17-24

Find the full text: https://scholar.archive.org/work/umtvk3iyxzflnpjboxfwla73uu/access/wayback/https://www.physiology.org/doi/pdf/10.1152/physiolgenomics.00179.2002

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Type: Journal Article

Serial number: 2904