Aluminium exposure disrupts elemental homeostasis in Caenorhabditis elegans

Page, Kathryn; White, Kenneth; McCrohan, Catherine R.; Killilea, David W.; Lithgow, Gordon J.

doi:10.1039/c2mt00146b

Cited by 21 publications

(12 citation statements)

References 68 publications

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“…ICP analysis was conducted as previously described 37 . Briefly, synchronized populations of arrested L1s were grown en masse (25,000-40,000 worms) at 25°C to induce sterility in the temperature-sensitive mutant, spe-9(hc88) .…”

Section: Methodsmentioning

confidence: 99%

Manganese disturbs metal and protein homeostasis in Caenorhabditis elegans

et al. 2014

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Parkinson's disease (PD) is a debilitating motor and cognitive neurodegenerative disorder for which there is no cure. While aging is the major risk factor for developing PD, clear environmental risks have also been identified. Environmental exposure to the metal manganese (Mn) is a prominent risk factor for developing PD and occupational exposure to high levels of Mn can cause a syndrome known as manganism, which has symptoms that closely resemble PD. In this study, we developed a model of manganism in the environmentally tractable nematode, Caenorhabditis elegans. We find that, in addition to previously described modes of Mn toxicity, which primarily include mitochondrial dysfunction and oxidative stress, Mn exposure also significantly antagonizes protein homeostasis, another key pathological feature associated with PD and many age-related neurodegenerative diseases. Mn treatment activates the ER unfolded protein response, severely exacerbates toxicity in a disease model of protein misfolding, and alters aggregate solubility. Further, aged animals, which have previously been shown to exhibit decreased protein homeostasis, are particularly susceptible to Mn toxicity when compared to young animals, indicating the aging process sensitizes animals to metal toxicity. Mn exposure also significantly alters iron (Fe) and calcium (Ca) homeostasis, which are important for mitochondrial and ER health and which may further compound toxicity. These finding indicate that modeling manganism in C. elegans can provide a useful platform for identifying therapeutic interventions for ER stress, proteotoxicity, and age-dependent susceptibilities, key pathological features of PD and other related neurodegenerative diseases.

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Section: Methodsmentioning

confidence: 99%

Manganese disturbs metal and protein homeostasis in Caenorhabditis elegans

et al. 2014

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“…Elemental content was normalized to the dry weight of the tissue. Quality control and analytical procedures were performed as previously described (33). Further dilutions of the samples were used where necessary to obtain results for highly abundant elements.…”

Section: Studymentioning

confidence: 99%

Hamp1 mRNA and plasma hepcidin levels are influenced by sex and strain but do not predict tissue iron levels in inbred mice

McLachlan

Page

Lee

et al. 2017

American Journal of Physiology-Gastrointestinal and Liver Physi

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Iron homeostasis is tightly regulated, and the peptide hormone hepcidin is considered to be a principal regulator of iron metabolism. Previous studies in a limited number of mouse strains found equivocal sex- and strain-dependent differences in mRNA and serum levels of hepcidin and reported conflicting data on the relationship between hepcidin () mRNA levels and iron status. Our aim was to clarify the relationships between strain, sex, and hepcidin expression by examining multiple tissues and the effects of different dietary conditions in multiple inbred strains. Two studies were done: first, mRNA, liver iron, and plasma diferric transferrin levels were measured in 14 inbred strains on a control diet; and second, mRNA and plasma hepcidin levels in both sexes and iron levels in the heart, kidneys, liver, pancreas, and spleen in males were measured in nine inbred/recombinant inbred strains raised on an iron-sufficient or high-iron diet. Both sex and strain have a significant effect on both hepcidin mRNA (primarily a sex effect) and plasma hepcidin levels (primarily a strain effect). However, liver iron and diferric transferrin levels are not predictors of mRNA levels in mice fed iron-sufficient or high-iron diets, nor are the mRNA and plasma hepcidin levels good predictors of tissue iron levels, at least in males. We also measured plasma erythroferrone, performed RNA-sequencing analysis of liver samples from six inbred strains fed the iron-sufficient, low-iron, or high-iron diets, and explored differences in gene expression between the strains with the highest and lowest hepcidin levels. Both sex and strain have a significant effect on both hepcidin mRNA (primarily a sex effect) and plasma hepcidin levels (primarily a strain effect). Liver iron and diferric transferrin levels are not predictors of mRNA levels in mice, nor are the mRNA and plasma hepcidin levels good predictors of tissue iron levels, at least in males.

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“…Although the physiological requirement for Al has yet to be defined, it has been posited that Al may have an etiopathogenic role in neurodegenerative diseases (Halatek et al, 2005). Studies with Al in the form of AlCl 3 , Al(NO 3 ) 3 , or Al 2 (SO 4 ) 3 identified phenotypic abnormalities, including toxic effects on lifespan, body size, development, reproduction, locomotion, behavioral plasticity, and memory in the worm (Wang et al, 2009; Page et al, 2012). Additionally, Page et al showed changes in elemental composition of whole worms exposed to Al, noting a significant increase in multiple metals and ensuing oxidative stress (Ba, Fe, Cr, and Cu), hypothesizing that altered levels of these elements contributed to the aforementioned phenotypes seen in chronic Al toxicity (Page et al, 2012).…”

Section: Techniques For Studying Neurodegeneration In C Elegansmentioning

confidence: 99%

Metal-induced neurodegeneration in C. elegans

Chen¹,

Martinez-Finley²,

Bornhorst³

et al. 2013

Front. Aging Neurosci.

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The model species, Caenorhabditis elegans, has been used as a tool to probe for mechanisms underlying numerous neurodegenerative diseases. This use has been exploited to study neurodegeneration induced by metals. The allure of the nematode comes from the ease of genetic manipulation, the ability to fluorescently label neuronal subtypes, and the relative simplicity of the nervous system. Notably, C. elegans have approximately 60–80% of human genes and contain genes involved in metal homeostasis and transport, allowing for the study of metal-induced degeneration in the nematode. This review discusses methods to assess degeneration as well as outlines techniques for genetic manipulation and presents a comprehensive survey of the existing literature on metal-induced degeneration studies in the worm.

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Aluminium exposure disrupts elemental homeostasis in Caenorhabditis elegans

Cited by 21 publications

References 68 publications

Manganese disturbs metal and protein homeostasis in Caenorhabditis elegans

Manganese disturbs metal and protein homeostasis in Caenorhabditis elegans

Hamp1 mRNA and plasma hepcidin levels are influenced by sex and strain but do not predict tissue iron levels in inbred mice

Metal-induced neurodegeneration in C. elegans

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