N,N’ bis-(2-mercaptoethyl) isophthalamide induces developmental delay in Caenorhabditis elegans by promoting DAF-16 nuclear localization
N,N’ bis-(2-mercaptoethyl) isophthalamide (NBMI) is a lipophilic thiol-containing agent that has high affinity for toxic metal ions, such as Hg2+, Pb2+, and Cd2+. Studies have shown that NBMI is a potent chelator of heavy metals, yet its potential toxicity in animals has yet to be determined. Using...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-01-01
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| Series: | Toxicology Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214750020303577 |
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| author | Tao Ke Félix Alexandre Antunes Soares Abel Santamaría Aaron B. Bowman Anatoly V. Skalny Michael Aschner |
| author_facet | Tao Ke Félix Alexandre Antunes Soares Abel Santamaría Aaron B. Bowman Anatoly V. Skalny Michael Aschner |
| author_sort | Tao Ke |
| collection | DOAJ |
| description | N,N’ bis-(2-mercaptoethyl) isophthalamide (NBMI) is a lipophilic thiol-containing agent that has high affinity for toxic metal ions, such as Hg2+, Pb2+, and Cd2+. Studies have shown that NBMI is a potent chelator of heavy metals, yet its potential toxicity in animals has yet to be determined. Using the model organism Caenorhabditis elegans (C. elegans), we show no significant change in worms’ death rate or lifespan following NBMI treatment (10−1000 μM). However, NBMI treatment was associated with a significant developmental delay. To determine if the daf-2/age-1/daf-16 pathway is involved in NBMI toxicity, mRNA levels of these genes were assessed in worms treated with NBMI. Here, we found that while NBMI failed to significantly alter the expression of daf-16 or daf-2; age-1 was significantly downregulated by NBMI. Furthermore, NBMI significantly increased DAF-16 nuclear localization. Consistent with a role for this pathway in NBMI toxicity, the developmental arrest by NBMI was more prominent in the DAF-16 transgenic strain than in the wild type N2 strain. Moreover, in the mutant strains harboring null alleles of daf-16, NBMI had no effect on development. In addition, NBMI repressed the expression of detoxifying genes (skn-1, gst-4 and gcs-1). In summary, NBMI has a low developmental toxicity in the C. elegans model, and the nuclear translocation of DAF-16 is involved in the developmental effect of NBMI. |
| first_indexed | 2024-12-17T00:18:45Z |
| format | Article |
| id | doaj.art-2067e2270bb248739c247d213bf90227 |
| institution | Directory Open Access Journal |
| issn | 2214-7500 |
| language | English |
| last_indexed | 2024-12-17T00:18:45Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Toxicology Reports |
| spelling | doaj.art-2067e2270bb248739c247d213bf902272022-12-21T22:10:38ZengElsevierToxicology Reports2214-75002020-01-017930937N,N’ bis-(2-mercaptoethyl) isophthalamide induces developmental delay in Caenorhabditis elegans by promoting DAF-16 nuclear localizationTao Ke0Félix Alexandre Antunes Soares1Abel Santamaría2Aaron B. Bowman3Anatoly V. Skalny4Michael Aschner5Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, 10461, United StatesDepartment of Biochemistry and Molecular Biology, Federal University of Santa Maria, Santa Maria, RS, BrazilLaboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurología y Neurocirugía, 14269, Mexico City, MexicoSchool of Health Sciences, Purdue University, West Lafayette, IN 47907-2051, United StatesYaroslavl State University, Sovetskaya St., 14, Yaroslavl 150000, RussiaDepartment of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, 10461, United States; Corresponding author: 1300 Morris Park Avenue Forchheimer Building, Room 209, Bronx, NY 10461 United States.N,N’ bis-(2-mercaptoethyl) isophthalamide (NBMI) is a lipophilic thiol-containing agent that has high affinity for toxic metal ions, such as Hg2+, Pb2+, and Cd2+. Studies have shown that NBMI is a potent chelator of heavy metals, yet its potential toxicity in animals has yet to be determined. Using the model organism Caenorhabditis elegans (C. elegans), we show no significant change in worms’ death rate or lifespan following NBMI treatment (10−1000 μM). However, NBMI treatment was associated with a significant developmental delay. To determine if the daf-2/age-1/daf-16 pathway is involved in NBMI toxicity, mRNA levels of these genes were assessed in worms treated with NBMI. Here, we found that while NBMI failed to significantly alter the expression of daf-16 or daf-2; age-1 was significantly downregulated by NBMI. Furthermore, NBMI significantly increased DAF-16 nuclear localization. Consistent with a role for this pathway in NBMI toxicity, the developmental arrest by NBMI was more prominent in the DAF-16 transgenic strain than in the wild type N2 strain. Moreover, in the mutant strains harboring null alleles of daf-16, NBMI had no effect on development. In addition, NBMI repressed the expression of detoxifying genes (skn-1, gst-4 and gcs-1). In summary, NBMI has a low developmental toxicity in the C. elegans model, and the nuclear translocation of DAF-16 is involved in the developmental effect of NBMI.http://www.sciencedirect.com/science/article/pii/S2214750020303577ChelationDevelopmental delayMethylmercuryC. elegans |
| spellingShingle | Tao Ke Félix Alexandre Antunes Soares Abel Santamaría Aaron B. Bowman Anatoly V. Skalny Michael Aschner N,N’ bis-(2-mercaptoethyl) isophthalamide induces developmental delay in Caenorhabditis elegans by promoting DAF-16 nuclear localization Toxicology Reports Chelation Developmental delay Methylmercury C. elegans |
| title | N,N’ bis-(2-mercaptoethyl) isophthalamide induces developmental delay in Caenorhabditis elegans by promoting DAF-16 nuclear localization |
| title_full | N,N’ bis-(2-mercaptoethyl) isophthalamide induces developmental delay in Caenorhabditis elegans by promoting DAF-16 nuclear localization |
| title_fullStr | N,N’ bis-(2-mercaptoethyl) isophthalamide induces developmental delay in Caenorhabditis elegans by promoting DAF-16 nuclear localization |
| title_full_unstemmed | N,N’ bis-(2-mercaptoethyl) isophthalamide induces developmental delay in Caenorhabditis elegans by promoting DAF-16 nuclear localization |
| title_short | N,N’ bis-(2-mercaptoethyl) isophthalamide induces developmental delay in Caenorhabditis elegans by promoting DAF-16 nuclear localization |
| title_sort | n n bis 2 mercaptoethyl isophthalamide induces developmental delay in caenorhabditis elegans by promoting daf 16 nuclear localization |
| topic | Chelation Developmental delay Methylmercury C. elegans |
| url | http://www.sciencedirect.com/science/article/pii/S2214750020303577 |
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