Fluazinam targets mitochondrial complex I to induce reactive oxygen species-dependent cytotoxicity in SH-SY5Y cells

Lee, Jeong Eun; Kang, Jungu; Ki, Yeo-Woon; Park, Jae Hyeon; Shin, In Chul; Koh, Hyun Chul

doi:10.1016/j.neuint.2012.03.007

Cited by 21 publications

(10 citation statements)

References 45 publications

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“…3). Additional chemicals that induced changes consistent with Cluster 2 included tebunfenpyrad, diquat dibromide, fenazaquin, fluazinam, diphenylamine, difenzoquat metilsulfate, myxothiazol, vincristine, and kresoxim-methyl, as well as mixtures of either pyraclostrobin or kresoxim-methyl with boscalid, each of which have a mechanism of action related to mitochondrial electron transport, oxidative phosphorylation, and/or microtubule destabilization 23–28 . RASL-seq also recapitulated the expression profiles for topoisomerase inhibitors, which downregulate expression of long synaptic genes 9,20 (Fig.…”

Section: Resultsmentioning

confidence: 99%

High-throughput screening and classification of chemicals and their effects on neuronal gene expression using RASL-seq

Simon

Paranjape

Wolter

et al. 2019

Sci Rep

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We previously used RNA-seq to identify chemicals whose effects on neuronal gene expression mimicked transcriptional signatures of autism, aging, and neurodegeneration. However, this approach was costly and time consuming, which limited our study to testing a single chemical concentration on mixed sex cortical neuron cultures. Here, we adapted a targeted transcriptomic method (RASL-seq, similar to TempO-seq) to interrogate changes in expression of a set of 56 signature genes in response to a library of 350 chemicals and chemical mixtures at four concentrations in male and female mouse neuronal cultures. This enabled us to replicate and expand our previous classifications, and show that transcriptional responses were largely equivalent between sexes. Overall, we found that RASL-seq can be used to accelerate the pace at which chemicals and mixtures that transcriptionally mimic autism and other neuropsychiatric diseases can be identified, and provides a cost-effective way to quantify gene expression with a panel of marker genes.

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Section: Resultsmentioning

confidence: 99%

High-throughput screening and classification of chemicals and their effects on neuronal gene expression using RASL-seq

Simon

Paranjape

Wolter

et al. 2019

Sci Rep

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“…In addition, it was interesting to note that the NADH dehydrogenase subunit 7 was significantly up-regulated (change fold = 1.505) in response to SYP-14288. This protein, which is one of the main sources of superoxide and is responsible for the translocation four protons across the mitochondrial membrane, has previously been reported to be the primary target of the uncoupler Fluazinam (Lee et al, 2012), which can be taken as further evidence that the two fungicides have shared a mode of action.…”

Section: Discussionmentioning

confidence: 98%

Insights from the proteome profile of Phytophthora capsici in response to the novel fungicide SYP-14288

Cai

Wang

et al. 2019

PeerJ

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Phytophthora capsica is a destructive oomycete plant pathogen that causes huge losses to crop production worldwide. However, the novel fungicide SYP-14288 has shown excellent activity against various stages of the oomycete life cycle as well against fungal plant pathogens. The current study utilized isobaric tags for relative and absolute quantitation technology to generate proteome profiles of P. capsici in the presence or absence of SYP-14288 in order to gain a greater understanding of the SYP-14288 mode of action. A total of 1,443 individual proteins were identified during the investigation, of which 599 were considered to have significantly altered expression. Further investigation using Cluster of Orthologous Groups of proteins analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated most of the proteins with altered expression were associated with carbohydrate metabolism, energy metabolism and their downstream biological functions, especially with regard to oxidoreductase activity and subsequent adenosine triphosphate (ATP) production associated pathways. Quantitative expression analysis using qRT-PCR validated the proteomic data. These results seem to indicate that SYP-14288 treatment caused a shift in energy metabolism that resulted in the activation of compensatory mechanisms affecting carbohydrate and lipid metabolism. The study also found evidence that the up-regulation of transmembrane transporters and proteins associated with stress response might also be coopted to compensate for the disrupted proton gradient and other downstream effects. Taken together these results provide strong evidence that SYP-14288 has a similar mode of action to the oxidative phosphorylation uncoupler Fluazinam but further investigation, including molecular studies, is required to completely characterize the SYP-14288 mode of action in P. capsici. However, the proteomic data collected in the current study does provide important insight into the overall effect of SYP-14288 in P. capsici, which could be useful for the registration and application of this novel fungicide.

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“…However, the repetitive use of lime destroys the soil structure, ultimately affecting sustainable production (Webster and Dixon 1991). Fluazinam, a synthetic fungicide, has been shown to control P. brassicae (Howard et al 2010;Yuan et al 2016), however, improper use of the soil and plant residues greatly affects human health and environmental safety (Lee et al 2012). Endophytic actinomycetes isolated from the roots of Chinese cabbage can effectively control clubroot (Lee et al 2008), but the activity against P. brassicae is susceptible to soil environmental conditions, and their field efficacy is inconsistent and often ineffective (Saravanan et al 2003;Mcgrann et al 2017).…”

Section: Introductionmentioning

confidence: 99%

Plasmodiophora brassicae in Yunnan and its Resistant Sources in Chinese Cabbage

Han¹

2021

IJAB

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The Williams differential system was employed for pathotype identification of 34 Plasmodiophora brassicaeroot samples collected from Yunnan Province and pathotypes 1, 2, 4, 10 and 14 were detected. Pathotype 4 was dominant with 70.59% of all the samples in Yunnan. The distribution of the P. brassicae pathotypes was mapped. Resistance to P. brassicae (clubroot disease) was investigated in 22 Chinese cabbage cultivars and it was found that the cultivar Shangpin had multiple resistances and was immune while Shangpin CR527 and Shangpin CR523 were resistant to P. brassicae. These cultivars can be used by farmers as sources of resistance to P. brassicae, to aid them in reducing disease in their crops. Seven known clubroot-resistant genes were detected in the 22 Chinese cabbage cultivars. CRa and CRb were found to be the most resistant to P. brassicae pathotype 4. Beisheng CR12 was resistant to pathotypes 1, 4, 10 and 14, but did not carry any known resistance genes, which indicated that unknown resistant genes were present. This study will lay the foundation for the control of clubroot disease and promote disease-resistant breeding of Chinese cabbage. © 2021 Friends Science Publishers

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Fluazinam targets mitochondrial complex I to induce reactive oxygen species-dependent cytotoxicity in SH-SY5Y cells

Cited by 21 publications

References 45 publications

High-throughput screening and classification of chemicals and their effects on neuronal gene expression using RASL-seq

High-throughput screening and classification of chemicals and their effects on neuronal gene expression using RASL-seq

Insights from the proteome profile of Phytophthora capsici in response to the novel fungicide SYP-14288

Plasmodiophora brassicae in Yunnan and its Resistant Sources in Chinese Cabbage

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