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Fluorodeoxyuridine Improves Caenorhabditis elegans Proteostasis Independent of Reproduction Onset

Protein homeostasis (proteostasis) networks are dynamic throughout the lifespan of an organism. During Caenorhabditis elegans adulthood, the maintenance of metastable proteins and the activation of stress responses are inversely associated with germline stem cell proliferation. Here, we employed the...

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Detalles Bibliográficos
Autores principales: Feldman, Naama, Kosolapov, Libby, Ben-Zvi, Anat
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897603/
https://www.ncbi.nlm.nih.gov/pubmed/24465816
http://dx.doi.org/10.1371/journal.pone.0085964
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author Feldman, Naama
Kosolapov, Libby
Ben-Zvi, Anat
author_facet Feldman, Naama
Kosolapov, Libby
Ben-Zvi, Anat
author_sort Feldman, Naama
collection PubMed
description Protein homeostasis (proteostasis) networks are dynamic throughout the lifespan of an organism. During Caenorhabditis elegans adulthood, the maintenance of metastable proteins and the activation of stress responses are inversely associated with germline stem cell proliferation. Here, we employed the thymidylate synthase inhibitor 5-fluoro-2′-deoxyuridine (FUdR) to chemically inhibit reproduction, thus allowing for examination of the interplay between reproduction and somatic proteostasis. We found that treatment with FUdR modulates proteostasis decline both before and after reproduction onset, such that effective induction of the heat shock response was maintained during adulthood and that metastable temperature-sensitive mutant phenotypes were rescued under restrictive conditions. However, FUdR treatment also improved the folding capacity of germline- and gonadogenesis-defective mutants, suggesting that proteostasis modulation by FUdR is independent of germline stem cell proliferation or inhibition of reproduction. Our data, therefore, indicate that FUdR converges on alternative regulatory signals that modulate C. elegans proteostasis capacity during development and adulthood.
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spelling pubmed-38976032014-01-24 Fluorodeoxyuridine Improves Caenorhabditis elegans Proteostasis Independent of Reproduction Onset Feldman, Naama Kosolapov, Libby Ben-Zvi, Anat PLoS One Research Article Protein homeostasis (proteostasis) networks are dynamic throughout the lifespan of an organism. During Caenorhabditis elegans adulthood, the maintenance of metastable proteins and the activation of stress responses are inversely associated with germline stem cell proliferation. Here, we employed the thymidylate synthase inhibitor 5-fluoro-2′-deoxyuridine (FUdR) to chemically inhibit reproduction, thus allowing for examination of the interplay between reproduction and somatic proteostasis. We found that treatment with FUdR modulates proteostasis decline both before and after reproduction onset, such that effective induction of the heat shock response was maintained during adulthood and that metastable temperature-sensitive mutant phenotypes were rescued under restrictive conditions. However, FUdR treatment also improved the folding capacity of germline- and gonadogenesis-defective mutants, suggesting that proteostasis modulation by FUdR is independent of germline stem cell proliferation or inhibition of reproduction. Our data, therefore, indicate that FUdR converges on alternative regulatory signals that modulate C. elegans proteostasis capacity during development and adulthood. Public Library of Science 2014-01-21 /pmc/articles/PMC3897603/ /pubmed/24465816 http://dx.doi.org/10.1371/journal.pone.0085964 Text en © 2014 Feldman et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Feldman, Naama
Kosolapov, Libby
Ben-Zvi, Anat
Fluorodeoxyuridine Improves Caenorhabditis elegans Proteostasis Independent of Reproduction Onset
title Fluorodeoxyuridine Improves Caenorhabditis elegans Proteostasis Independent of Reproduction Onset
title_full Fluorodeoxyuridine Improves Caenorhabditis elegans Proteostasis Independent of Reproduction Onset
title_fullStr Fluorodeoxyuridine Improves Caenorhabditis elegans Proteostasis Independent of Reproduction Onset
title_full_unstemmed Fluorodeoxyuridine Improves Caenorhabditis elegans Proteostasis Independent of Reproduction Onset
title_short Fluorodeoxyuridine Improves Caenorhabditis elegans Proteostasis Independent of Reproduction Onset
title_sort fluorodeoxyuridine improves caenorhabditis elegans proteostasis independent of reproduction onset
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897603/
https://www.ncbi.nlm.nih.gov/pubmed/24465816
http://dx.doi.org/10.1371/journal.pone.0085964
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