Air Pollution Alters Caenorhabditis elegans Development and Lifespan: Responses to Traffic-Related Nanoparticulate Matter

Haghani, Amin; Dalton, Hans M; Safi, Nikoo; Shirmohammadi, Farimah; Sioutas, Constantinos; Morgan, Todd E.; Finch, Caleb E.; Curran, Sean P.

doi:10.1093/gerona/glz063

Cited by 28 publications

(18 citation statements)

References 49 publications

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“…If particulate air pollution is a significant source of proteotoxic stress, we would expect it to trigger stress-responsive gene expression. In fact, the immediate transcriptional upregulation of some UPR targets such as the molecular chaperone gene hsp-4 and oxidative stress targets such as the antioxidant gene, gst-4 [12] has been recently reported for L1-stage wild type C. elegans exposed to nPM for 1hr. As at least some of the studies proposed here will involve chronic (3d) exposures to nPM, we aim to determine whether the expression of proteostasis network components responds to nPM stress over this time period.…”

Section: Can Alterations In Chaperone Gene Expression In Response mentioning

confidence: 98%

Section: Experimental Design and Rationalementioning

confidence: 99%

“…Consistent with this hypothesis, it was recently shown that the expression levels of proteostasis network genes in C . elegans are responsive to nPM [ 12 ]. Furthermore, the degradative pathways of the proteostasis network have also been shown to be activated in mice exposed to nPM [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Determining the effects of nanoparticulate air pollution on proteostasis in Caenorhabditis elegans

Green

Kikis

2020

PLoS ONE

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The proteostasis network comprises the biochemical pathways that together maintain and regulate proper protein synthesis, transport, folding, and degradation. Many neurodegenerative diseases are characterized by a failure of the proteostasis network to sustain the health of the proteome, resulting in protein misfolding, aggregation, and, often, neurotoxicity. Although important advances have been made in recent years to identify genetic risk factors for neurodegenerative diseases, we still know relatively little about environmental risk factors such as air pollution. Exposure to nano-sized particulate air pollution, referred to herein as nanoparticulate matter (nPM), has been shown to trigger the accumulation of misfolded and oligomerized amyloid beta in mice. This suggests that the ability to maintain proteostasis is likely compromised in Alzheimer ‘s disease (AD) pathogenesis upon exposure to nPM. We aim to determine whether this aspect of the environment interacts with proteostasis network machinery to trigger protein misfolding. This could at least partially explain how air pollution exacerbates the symptoms of neurodegenerative diseases of aging, such as AD. We hypothesize that nPM challenges the buffering capacity of the proteostasis network by reducing the efficiency of folding for metastable proteins, thereby disrupting what has proven to be a very delicate proteostasis balance. We will test this hypothesis using C. elegans as our model system. Specifically, we will determine the impact of particulate air pollution on the aggregation and toxicity of disease-associated reporters of proteostasis and on transcriptional responses to stress.

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Section: Can Alterations In Chaperone Gene Expression In Response mentioning

confidence: 98%

Section: Experimental Design and Rationalementioning

confidence: 99%

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Determining the effects of nanoparticulate air pollution on proteostasis in Caenorhabditis elegans

Green

Kikis

2020

PLoS ONE

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“…New primers used in this study are as follows: Lifespan analysis. Lifespan data was collected as previously described 40,[74][75][76] . In brief, plates containing synchronized populations were scored daily for survival, beginning at L4 stage.…”

Section: Rna Extraction and Gene Expressionmentioning

confidence: 99%

Roles for the RNA polymerase III regulator MAFR-1 in regulating sperm quality in Caenorhabditis elegans

Hammerquist¹,

Curran²

2020

Sci Rep

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The negative regulator of RNA polymerase (pol) III mafr-1 has been shown to affect RNA pol III transcript abundance, lipid biosynthesis and storage, progeny output, and lifespan. We deleted mafr-1 from the Caenorhabditis elegans genome and found that animals lacking mafr-1 replicated many phenotypes from previous RNAi-based studies and discovered a new sperm-specific role. Utilizing a yeast two-hybrid assay, we discovered several novel interactors of MAFR-1 that are expressed in a sperm- and germline-enriched manner. In support of a role for MAFR-1 in the male germline, we found mafr-1 null males have smaller spermatids that are less capable in competition for fertilization; a phenotype that was dependent on RNA pol III activity. Restoration of MAFR-1 expression specifically in the germline rescued the spermatid-related phenotypes, suggesting a cell autonomous role for MAFR-1 in nematode male fertility. Based on the high degree of conservation of Maf1 activity across species, our study may inform similar roles for Maf1 and RNA pol III in mammalian male fertility.

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“…Lifespan data was collected as previously described in the HT115 RNAi E. coli diet (Dalton and Curran, 2018;Haghani et al, 2019;Paek et al, 2012;Pang and Curran, 2014). In brief, plates containing synchronized populations were scored daily for survival, beginning at L4 stage.…”

Section: Lifespan Analysismentioning

confidence: 99%

Roles for the RNA polymerase III regulator MAFR-1 in regulating sperm quality inCaenorhabditis elegans

Hammerquist

Curran

2020

Preprint

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The negative regulator of RNA polymerase (pol) III mafr-1 has been shown to affect RNA pol III transcript abundance, lipid biosynthesis and storage, progeny output, and lifespan. We deleted mafr-1 from the Caenorhabditis elegans genome and found that animals lacking mafr-1 replicated many phenotypes from previous RNAi-based studies, but strikingly not the oocyte-related reproductive phenotypes. Utilizing a yeast two-hybrid assay, we discovered several novel interactors of MAFR-1 that are expressed in a sperm-and germline-enriched manner. In support of a role for MAFR-1 in the male germline, we found mafr-1 null males have smaller spermatids that are less capable in competition for fertilization; a phenotype that was dependent on RNA pol III activity. Restoration of MAFR-1 expression specifically in the germline rescued the spermatid-related phenotypes, suggesting a cell autonomous role for MAFR-1 in nematode male fertility. Based on the high degree of conservation of Maf1 activity across species, our study may inform similar roles for Maf1 and RNA pol III in mammalian male fertility.

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Air Pollution Alters Caenorhabditis elegans Development and Lifespan: Responses to Traffic-Related Nanoparticulate Matter

Cited by 28 publications

References 49 publications

Determining the effects of nanoparticulate air pollution on proteostasis in Caenorhabditis elegans

Determining the effects of nanoparticulate air pollution on proteostasis in Caenorhabditis elegans

Roles for the RNA polymerase III regulator MAFR-1 in regulating sperm quality in Caenorhabditis elegans

Roles for the RNA polymerase III regulator MAFR-1 in regulating sperm quality inCaenorhabditis elegans

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