Stress response pathways protect germ cells from omega-6 polyunsaturated fatty acid-mediated toxicity in Caenorhabditis elegans

Christopher M Webster; Marshall L Deline; Jennifer L Watts

doi:10.1016/j.ydbio.2012.10.002

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Stress response pathways protect germ cells from omega-6 polyunsaturated fatty acid-mediated toxicity in Caenorhabditis elegans

Journal article

Open access

Peer reviewed

Stress response pathways protect germ cells from omega-6 polyunsaturated fatty acid-mediated toxicity in Caenorhabditis elegans

Christopher M Webster, Marshall L Deline and Jennifer L Watts

Developmental biology, Vol.373(1), pp.14-25

01/01/2013

DOI: https://doi.org/10.1016/j.ydbio.2012.10.002

Handle:

https://hdl.handle.net/2376/110392

PMID: 23064027

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Abstract

Stress, Physiological - physiology

Species Specificity

Germ Cells - drug effects

Signal Transduction - genetics

Chromatography, Gas

Hot Temperature

Transcription Factors - genetics

8,11,14-Eicosatrienoic Acid - toxicity

DNA-Binding Proteins - genetics

Mutation - genetics

Germ Cells - physiology

Caenorhabditis elegans

Insulin - metabolism

Animals

RNA Interference

Cell Death - drug effects

Indoles

Infertility - etiology

Caenorhabditis elegans Proteins - genetics

Dietary Fats - toxicity

Real-Time Polymerase Chain Reaction

Cell Membrane - drug effects

Microscopy, Fluorescence

Polyunsaturated fatty acids serve both structural and functional roles as membrane components and precursors for a number of different factors involved in inflammation and signaling. These fatty acids are required in the human diet, although excess dietary intake of omega-6 fatty polyunsaturated fatty acids may have a negative influence on human health. In the model nematode, Caenorhabditis elegans, dietary exposure to dihomo-gamma-linolenic acid (DGLA), an omega-6 fatty acid, causes the destruction of germ cells and leads to sterility. In this study we used genetic and microscopic approaches to further characterize this phenomenon. We found that strains carrying mutations in genes involved in lipid homeostasis enhanced sterility phenotypes, while mutations reducing the activity of the conserved insulin/IGF signaling pathway suppressed sterility phenotypes. Exposure to a mild heat stress prior to omega-6 fatty acid treatment led to an adaptive or hormetic response, resulting in less sterility. Mutations in skn-1 and knockdown of genes encoding phase II detoxification enzymes led to increased sterility in the presence of dietary DGLA. Thus, detoxification systems and genetic changes that increase overall stress responses protect the germ cells from destruction. Microscopic analyses revealed that dietary DGLA leads to deterioration of germ cell membranes in the proliferative and transition zones of the developing germ line. Together, these data demonstrate that specific omega-6 polyunsaturated fatty acids, or molecules derived from them, are transported to the germ line where they disrupt the rapidly expanding germ cell membranes, leading to germ cell death.

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Title: Stress response pathways protect germ cells from omega-6 polyunsaturated fatty acid-mediated toxicity in Caenorhabditis elegans
Creators: Christopher M Webster - School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, WA 99614-6340, USA
Marshall L Deline
Jennifer L Watts
Publication Details: Developmental biology, Vol.373(1), pp.14-25
Academic Unit: Molecular Biosciences, School of
Publisher: United States
Grant note: R01 DK74114 / NIDDK NIH HHS R01 DK074114 / NIDDK NIH HHS
Identifiers: 99900547122401842
Language: English
Resource Type: Journal article