Effects of an azasteroid on growth, development and reproduction of the free-living nematodes Caenorhabditis briggsae and Panagrellus redivivus

Bottjer, Kurt P.; Weinstein, Paul P.; Thompson, Malcolm J.

doi:10.1016/0305-0491(85)90135-x

Cited by 15 publications

(10 citation statements)

References 20 publications

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“…This abnormal cuticle development coincided with reduced motility in the drug-treated group (data not shown). Therefore, azacoprostane treatment seemed to cause an insufficient sterol supply leading to serious defects in growth, development, and the sterol-mediated reproductive system in C. elegans, as consistent with previous reports (8,11).…”

Section: Resultssupporting

confidence: 79%

“…As anticipated from the previously reported case of C. briggsae (11), there was a significant reduction in brood size (average 30% decrease, n ϭ 20) and an increase in embryonic lethality (average 80% increase, n ϭ 20) and growth retardation in the azacoprostane-treated group (data not shown). Furthermore, serious defects in gonads (i.e.…”

Section: Resultssupporting

confidence: 71%

“…Azacoprostane has also been known to inhibit viability and microfilarial production in the nematode Brugia pahangi (15). There was a significant reduction in growth, reproductive capability, and the percent development of the embryo to the adult in azacoprostane-treated Caenorhabditis briggsae (11).…”

mentioning

confidence: 88%

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Proteomic Changes during Disturbance of Cholesterol Metabolism by Azacoprostane Treatment in Caenorhabditis elegans

Choi

Chitwood

Paik

2003

Molecular & Cellular Proteomics

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Although nematodes like Caenorhabditis elegans are incapable of de novo cholesterol biosynthesis, they can utilize nonfunctional sterols by converting them into cholesterol and other sterols for cellular function. The results reported previously and presented here suggest that blocking of sterol conversion to cholesterol in C. elegans by 25-azacoprostane-HCl (azacoprostane) treatment causes a serious defect in germ cell development, growth, cuticle development, and motility behavior. To establish a biochemical basis for these physiological abnormalities, we performed proteomic analysis of mixed stage worms that had been treated with the drug. Our results from a differential display proteomic analysis revealed significant decreases in the levels of proteins involved in collagen and cytoskeleton organization such as protein disulfide isomerase (6.7-fold), ␤-tubulin (5.41-fold), and NEX-1 protein (>30-fold). Also reduced were enzymes involved in energy production such as phosphoglycerate kinase (4.8-fold) and phosphoenolpyruvate carboxykinase (8.5-fold), a target for antifilarial drugs such as azacoprostane. In particular, reductions in the expression of lipoprotein families such as vitellogenin-2 (7.7-fold) and vitellogenin-6 (5.4-fold) were prominent in the drug-treated worms, indicating that sterol metabolism disturbance caused by azacoprostane treatment is tightly coupled with suppression of the lipid transfer-related proteins at the protein level. However, competitive quantitative reverse transcriptase polymerase chain reaction showed that the transcriptional levels of vit-2, vit-6, and their receptors (e.g. rme-2 and lrp-1) in drug-treated worms were 3-to 5-fold higher than those in the untreated group, suggesting a presence of a sterol regulatory element-binding protein (SREBP)-like pathway in these genes. In fact, multiple predicted sterol regulatory elements or related regulatory sequences responding to sterols were found to be located at the 5-flanking regions in vit-2 and lrp-1 genes, and their transcriptional activities fluctuated highly in response to changes in sterol concentration. Thus, many physiological abnormalities caused by azacoprostanemediated sterol metabolism disturbance appear to be exerted at least in part through SREBP pathway in C. elegans.Molecular & Cellular

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Section: Resultssupporting

confidence: 79%

Section: Resultssupporting

confidence: 71%

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Proteomic Changes during Disturbance of Cholesterol Metabolism by Azacoprostane Treatment in Caenorhabditis elegans

Choi

Chitwood

Paik

2003

Molecular & Cellular Proteomics

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“…Our experiments, and published studies, show that cholesterol accumulation in sperm per se is not necessary for fertilization. For instance, it is known that cholesterol depletion by growth on cholesterol-free medium or growth on 25-azacoprostane, a nonfunctional analog of cholesterol, has no visible effect on the first generation of treated animals (Chitwood et al, 1984;Bottjer et al, 1985;Yochem et al, 1999). Only the second generation shows defects in molting and growth.…”

Section: Enrichment Of Cholesterol In Germ Line Cellsmentioning

confidence: 99%

“…Worms grown on plates depleted of cholesterol display defects in molting (Yochem et al, 1999). If cholesterol is substituted by its nonfunctional analog 25-azacoprostane, growth and reproduction of animals is strongly inhibited (Chitwood et al, 1984;Bottjer et al, 1985). Recently, while investigating the function of a C. elegans homologue of caveolin, we found that the cholesterol level in gonads influences signal transduction (Scheel et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Distribution and Transport of Cholesterol inCaenorhabditis elegans

Matyash

Geier

Henske

et al. 2001

MBoC

162

164

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Cholesterol transport is an essential process in all multicellular organisms. In this study we applied two recently developed approaches to investigate the distribution and molecular mechanisms of cholesterol transport in Caenorhabditis elegans. The distribution of cholesterol in living worms was studied by imaging its fluorescent analog, dehydroergosterol, which we applied to the animals by feeding. Dehydroergosterol accumulates primarily in the pharynx, nerve ring, excretory gland cell, and gut of L1-L3 larvae. Later, the bulk of dehydroergosterol accumulates in oocytes and spermatozoa. Males display exceptionally strong labeling of spermatids, which suggests a possible role for cholesterol in sperm development. In a complementary approach, we used a photoactivatable cholesterol analog to identify cholesterol-binding proteins in C. elegans. Three major and several minor proteins were found specifically cross-linked to photocholesterol after UV irradiation. The major proteins were identified as vitellogenins. rme-2 mutants, which lack the vitellogenin receptor, fail to accumulate dehydroergosterol in oocytes and embryos and instead accumulate dehydroergosterol in the body cavity along with vitellogenin. Thus, uptake of cholesterol by C. elegans oocytes occurs via an endocytotic pathway involving yolk proteins. The pathway is a likely evolutionary ancestor of mammalian cholesterol transport.

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Nematodes

Bodri

2021

Invertebrate Medicine

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Effects of an azasteroid on growth, development and reproduction of the free-living nematodes Caenorhabditis briggsae and Panagrellus redivivus

Cited by 15 publications

References 20 publications

Proteomic Changes during Disturbance of Cholesterol Metabolism by Azacoprostane Treatment in Caenorhabditis elegans

Proteomic Changes during Disturbance of Cholesterol Metabolism by Azacoprostane Treatment in Caenorhabditis elegans

Distribution and Transport of Cholesterol inCaenorhabditis elegans

Nematodes

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