{"title":"手稿已提交:Chemico-Biological Interactions CHEMBIOINT-D-24-02395-R3 早期长期暴露于黄曲霉毒素 B1 会诱导衰老并改变草履虫与 SKN-1/Nrf2 相关的先天免疫。","authors":"Tzu-Ting Chang, Chun-Han Chang, Vivian Hsiu-Chuan Liao","doi":"10.1016/j.cbi.2024.111349","DOIUrl":null,"url":null,"abstract":"<div><div>Aflatoxin B1 (AFB1), a known human carcinogen, represents the most toxic aflatoxin metabolite. Exposure to AFB1 causes increased oxidative stress and immunotoxicity, which are important factors contributing to aging. However, the role of AFB1-induced toxicity in altered innate immunity and aging remains largely unclear. The nematode <em>Caenorhabditis elegans</em> is a suitable model organism for studying aging and toxicology due to its well-studied molecular mechanisms and short life cycle. Effects of AFB1 at 1, 2.5, and 5 μM (312, 781, and 1561 μg/L) on growth, reproduction, and lifespan were examined. The <em>Pseudomonas aeruginosa</em> PA14 slow-killing assay was performed to investigate innate immunity, followed by studying the possible mechanisms using transgenic strains and qPCR analysis. The results showed that early life long-term AFB1 exposure (2.5 and 5 μM) delayed development, reduced reproduction, and shortened lifespan in <em>C. elegans</em>. Furthermore, in aged worms, AFB1 exposure caused a dose-dependent decrease in survival of <em>C. elegans</em> against <em>P. aeruginosa</em> PA14 infection. At adulthood day 4 in the presence of live <em>Escherichia coli</em> OP50, AFB1 (2.5 μM) significantly increased lipofuscin levels (a hallmark of aging) compared to adult day 0, whereas no increase in lipofuscin was observed in nematodes (adulthood day 4) fed with dead <em>E. coli</em> OP50. Additionally, the increased lipofuscin was abolished in the <em>skn-1</em> mutant with either live or dead <em>E. coli</em> OP50. Furthermore, AFB1 suppressed intestinal SKN-1::GFP translocation. Two-way ANOVA analysis revealed that the activity of <em>E. coli</em> OP50 and AFB1 interactively affected the expression of genes: <em>skn-1</em>, <em>gst-4</em>, <em>hsp-16.1</em>, <em>hsp-16.49</em>, and <em>hsp-70</em>. Our findings highlight the role of AFB1-induced toxicity in altered innate immunity and aging through the involvement of the transcription factor SKN-1/Nrf2.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"406 ","pages":"Article 111349"},"PeriodicalIF":4.7000,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Early life long-term exposure to aflatoxin B1 induces aging and alters innate immunity associated with SKN-1/Nrf2 in Caenorhabditis elegans\",\"authors\":\"Tzu-Ting Chang, Chun-Han Chang, Vivian Hsiu-Chuan Liao\",\"doi\":\"10.1016/j.cbi.2024.111349\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Aflatoxin B1 (AFB1), a known human carcinogen, represents the most toxic aflatoxin metabolite. Exposure to AFB1 causes increased oxidative stress and immunotoxicity, which are important factors contributing to aging. However, the role of AFB1-induced toxicity in altered innate immunity and aging remains largely unclear. The nematode <em>Caenorhabditis elegans</em> is a suitable model organism for studying aging and toxicology due to its well-studied molecular mechanisms and short life cycle. Effects of AFB1 at 1, 2.5, and 5 μM (312, 781, and 1561 μg/L) on growth, reproduction, and lifespan were examined. The <em>Pseudomonas aeruginosa</em> PA14 slow-killing assay was performed to investigate innate immunity, followed by studying the possible mechanisms using transgenic strains and qPCR analysis. The results showed that early life long-term AFB1 exposure (2.5 and 5 μM) delayed development, reduced reproduction, and shortened lifespan in <em>C. elegans</em>. Furthermore, in aged worms, AFB1 exposure caused a dose-dependent decrease in survival of <em>C. elegans</em> against <em>P. aeruginosa</em> PA14 infection. At adulthood day 4 in the presence of live <em>Escherichia coli</em> OP50, AFB1 (2.5 μM) significantly increased lipofuscin levels (a hallmark of aging) compared to adult day 0, whereas no increase in lipofuscin was observed in nematodes (adulthood day 4) fed with dead <em>E. coli</em> OP50. Additionally, the increased lipofuscin was abolished in the <em>skn-1</em> mutant with either live or dead <em>E. coli</em> OP50. Furthermore, AFB1 suppressed intestinal SKN-1::GFP translocation. Two-way ANOVA analysis revealed that the activity of <em>E. coli</em> OP50 and AFB1 interactively affected the expression of genes: <em>skn-1</em>, <em>gst-4</em>, <em>hsp-16.1</em>, <em>hsp-16.49</em>, and <em>hsp-70</em>. Our findings highlight the role of AFB1-induced toxicity in altered innate immunity and aging through the involvement of the transcription factor SKN-1/Nrf2.</div></div>\",\"PeriodicalId\":274,\"journal\":{\"name\":\"Chemico-Biological Interactions\",\"volume\":\"406 \",\"pages\":\"Article 111349\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2025-01-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Chemico-Biological Interactions\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0009279724004952\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chemico-Biological Interactions","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0009279724004952","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Early life long-term exposure to aflatoxin B1 induces aging and alters innate immunity associated with SKN-1/Nrf2 in Caenorhabditis elegans
Aflatoxin B1 (AFB1), a known human carcinogen, represents the most toxic aflatoxin metabolite. Exposure to AFB1 causes increased oxidative stress and immunotoxicity, which are important factors contributing to aging. However, the role of AFB1-induced toxicity in altered innate immunity and aging remains largely unclear. The nematode Caenorhabditis elegans is a suitable model organism for studying aging and toxicology due to its well-studied molecular mechanisms and short life cycle. Effects of AFB1 at 1, 2.5, and 5 μM (312, 781, and 1561 μg/L) on growth, reproduction, and lifespan were examined. The Pseudomonas aeruginosa PA14 slow-killing assay was performed to investigate innate immunity, followed by studying the possible mechanisms using transgenic strains and qPCR analysis. The results showed that early life long-term AFB1 exposure (2.5 and 5 μM) delayed development, reduced reproduction, and shortened lifespan in C. elegans. Furthermore, in aged worms, AFB1 exposure caused a dose-dependent decrease in survival of C. elegans against P. aeruginosa PA14 infection. At adulthood day 4 in the presence of live Escherichia coli OP50, AFB1 (2.5 μM) significantly increased lipofuscin levels (a hallmark of aging) compared to adult day 0, whereas no increase in lipofuscin was observed in nematodes (adulthood day 4) fed with dead E. coli OP50. Additionally, the increased lipofuscin was abolished in the skn-1 mutant with either live or dead E. coli OP50. Furthermore, AFB1 suppressed intestinal SKN-1::GFP translocation. Two-way ANOVA analysis revealed that the activity of E. coli OP50 and AFB1 interactively affected the expression of genes: skn-1, gst-4, hsp-16.1, hsp-16.49, and hsp-70. Our findings highlight the role of AFB1-induced toxicity in altered innate immunity and aging through the involvement of the transcription factor SKN-1/Nrf2.
期刊介绍:
Chemico-Biological Interactions publishes research reports and review articles that examine the molecular, cellular, and/or biochemical basis of toxicologically relevant outcomes. Special emphasis is placed on toxicological mechanisms associated with interactions between chemicals and biological systems. Outcomes may include all traditional endpoints caused by synthetic or naturally occurring chemicals, both in vivo and in vitro. Endpoints of interest include, but are not limited to carcinogenesis, mutagenesis, respiratory toxicology, neurotoxicology, reproductive and developmental toxicology, and immunotoxicology.