The effect of pentachlorophenol and its metabolite tetrachlorohydroquinone on RNA, protein, and ribosome synthesis in saccharomyces cells

Ehrlich, W.; Mangir, M.; Lochmann, Ernst-Randolf

doi:10.1016/0147-6513(87)90037-6

Cited by 8 publications

(4 citation statements)

References 12 publications

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“…First, intact cells normally contain 2 to 5 percent dsRNA in native heterogeneous nuclear ribonucleoproteins [ 36 , 37 ], which could potentially translocate to cytoplasm and activate PKR upon toxin treatment. Second, cytoplasmic poly (A)-rich RNA reportedly activates PKR in vitro and in vivo [ 38 , 39 , 40 , 41 ]. Since the HeLa lysate does not contain these cellular RNAs, it reduces the possibility of artifactual activation of PKR by them.…”

Section: Discussionmentioning

confidence: 99%

Direct Activation of Ribosome-Associated Double-Stranded RNA-Dependent Protein Kinase (PKR) by Deoxynivalenol, Anisomycin and Ricin: A New Model for Ribotoxic Stress Response Induction

Zhou

Landgraf

et al. 2014

Toxins

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Double-stranded RNA (dsRNA)-activated protein kinase (PKR) is a critical upstream mediator of the ribotoxic stress response (RSR) to the trichothecene deoxynivalenol (DON) and other translational inhibitors. Here, we employed HeLa cell lysates to: (1) characterize PKR’s interactions with the ribosome and ribosomal RNA (rRNA); (2) demonstrate cell-free activation of ribosomal-associated PKR and (3) integrate these findings in a unified model for RSR. Robust PKR-dependent RSR was initially confirmed in intact cells. PKR basally associated with 40S, 60S, 80S and polysome fractions at molar ratios of 7, 2, 23 and 3, respectively. Treatment of ATP-containing HeLa lysates with DON or the ribotoxins anisomycin and ricin concentration-dependently elicited phosphorylation of PKR and its substrate eIF2α. These phosphorylations could be blocked by PKR inhibitors. rRNA immunoprecipitation (RNA-IP) of HeLa lysates with PKR-specific antibody and sequencing revealed that in the presence of DON or not, the kinase associated with numerous discrete sites on both the 18S and 28S rRNA molecules, a number of which contained double-stranded hairpins. These findings are consistent with a sentinel model whereby multiple PKR molecules basally associate with the ribosome positioning them to respond to ribotoxin-induced alterations in rRNA structure by dimerizing, autoactivating and, ultimately, evoking RSR.

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Section: Discussionmentioning

confidence: 99%

Direct Activation of Ribosome-Associated Double-Stranded RNA-Dependent Protein Kinase (PKR) by Deoxynivalenol, Anisomycin and Ricin: A New Model for Ribotoxic Stress Response Induction

Zhou

Landgraf

et al. 2014

Toxins

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“…Our observation of dramatically reduced growth in the presence of increasing concentrations of PCP fits with previous studies in other organisms. PCP causes growth delays in Saccharomyces cerevisiae , human neuroblastoma cells, zebrafish embryos, and Helix aspersa ( Ehrlich et al, 1987 , Fraser et al, 2019 , Gomot-De Vaufleury, 2000 , Xu et al, 2014b ). The growth delay we observed in our study suggests that PCP causes similar developmental effects in C. elegans .…”

Section: Discussionmentioning

confidence: 99%

“…The growth delay we observed in our study suggests that PCP causes similar developmental effects in C. elegans . Studies in Saccharomyces cerevisiae suggest that these mechanisms may be targeting RNA production and ribosome synthesis, either by PCP itself or via a downstream metabolite ( Ehrlich et al 1987 ). If PCP exposure acts via analogous pathways in the worm, it is possible that developing larvae may not be producing adequate amounts of protein and are suffering growth delays as a result.…”

Section: Discussionmentioning

confidence: 99%

Mild pentachlorophenol-mediated uncoupling of mitochondria depletes ATP but does not cause an oxidized redox state or dopaminergic neurodegeneration in Caenorhabditis elegans

Markovich

Hartman

Ryde

et al. 2022

Current Research in Toxicology

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“…In vivo and in vitro experiments have suggested that PCP is a promoter of carcinogenesis in rodents (Chhabra et al , 1999), an endocrine disruptor and a probable carcinogen in humans (Proudfoot et al , 2003; Seiler et al , 1991). PCP has been shown to affect the endocrine system of vertebrate life forms (Beard et al , 1999) and is also reported to inhibit RNA and ribosome synthesis (Ehrlich et al , 1987). It causes adverse effects to the liver (Umemura et al , 1999; Kimbrough et al , 1978; Wang et al , 2001), kidneys, lungs, immune system (Blakley et al , 1998; Colosia et al , 1993) and gastrointestinal tract (Deichmann et al , 1942; George et al , 2006).…”

Section: Introductionmentioning

confidence: 99%

Chlorophenol stress affects aromatic amino acid biosynthesis—a genome‐wide study

Yadav

Shitiz

Pandey

et al. 2010

Yeast

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Chlorophenols are a class of chemicals commonly used in preservatives, disinfectants, algaecides, herbicides and pesticides. However, there is a growing evidence that these compounds are a threat to human health. This is alarming as many chlorophenols are common pollutants found in the global environment at potentially biohazardous levels. Despite chlorophenols being abundant, widely used and poisonous, we know relatively little about their mechanism of toxicity in eukaryotes. Thus, we performed genome-wide growth screens using Saccharomyces cerevisiae to understand the molecular basis of chlorophenol toxicity. Of ∼4850 single gene knockout strains tested, 393 mutants showed growth sensitivity to treatment with 4-chlorophenol (4-CP), 2,4-dichlorophenol (2,4-DCP) or pentachlorophenol (PCP). Only eight mutants showed growth hypersensitivity to all the three treatments and harboured deletions in genes important for aromatic amino acid biosynthesis (ARO1, ARO7 ) or mitochondrial protein synthesis and respiration (ATP5, ISA1, RML2, GET2, SLS1, MRPL38 ).

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The effect of pentachlorophenol and its metabolite tetrachlorohydroquinone on RNA, protein, and ribosome synthesis in saccharomyces cells

Cited by 8 publications

References 12 publications

Direct Activation of Ribosome-Associated Double-Stranded RNA-Dependent Protein Kinase (PKR) by Deoxynivalenol, Anisomycin and Ricin: A New Model for Ribotoxic Stress Response Induction

Direct Activation of Ribosome-Associated Double-Stranded RNA-Dependent Protein Kinase (PKR) by Deoxynivalenol, Anisomycin and Ricin: A New Model for Ribotoxic Stress Response Induction

Mild pentachlorophenol-mediated uncoupling of mitochondria depletes ATP but does not cause an oxidized redox state or dopaminergic neurodegeneration in Caenorhabditis elegans

Chlorophenol stress affects aromatic amino acid biosynthesis—a genome‐wide study

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