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p38 MAPK-SKN-1/Nrf signaling cascade is required for intestinal barrier against graphene oxide toxicity in Caenorhabditis elegans.
Nanotoxicology. 2016 12; 10(10):1469-1479.N

Abstract

Biological barrier plays a crucial role for organisms against the possible toxicity from engineered nanomaterials (ENMs). Graphene oxide (GO) has been proven to cause potential toxicity on organisms. However, the molecular mechanisms for intestinal barrier of animals against GO toxicity are largely unclear. Using in vivo assay system of Caenorhabditis elegans, we found that mutation of genes encoding core p38 mitogen-activated protein kinase (MAPK) signaling pathway caused susceptible property to GO toxicity and enhanced translocation of GO into the body of nematodes. Genetic assays indicated that SKN-1/Nrf functioned downstream of p38 MAPK signaling pathway to regulate GO toxicity and translocation. Transcription factor of SKN-1 could regulate GO toxicity and translocation at least through function of its targeted gene of gst-4 encoding one of phase II detoxification proteins. Moreover, intestine-specific RNA interference (RNAi) assay demonstrated that the p38 MAPK-SKN-1/Nrf signaling cascade could function in intestine to regulate GO toxicity and intestinal permeability in GO exposed nematodes. Therefore, p38 MAPK-SKN-1/Nrf signaling cascade may act as an important molecular basis for intestinal barrier against GO toxicity in organisms. Exposure to GO induced significantly increased expression of genes encoding p38 MAPK-SKN-1/Nrf signaling cascade, which further implies that the identified p38 MAPK-SKN-1/Nrf signaling cascade may encode a protection mechanism for nematodes in intestine to be against GO toxicity.

Authors+Show Affiliations

Zhao Y
a Key Laboratory of Environmental Medicine Engineering in Ministry of Education, Medical School, Southeast University , Nanjing , China , and. b Department of Preventive Medicine , Bengbu Medical College , Bengbu , China.
Zhi L
a Key Laboratory of Environmental Medicine Engineering in Ministry of Education, Medical School, Southeast University , Nanjing , China , and.
Wu Q
a Key Laboratory of Environmental Medicine Engineering in Ministry of Education, Medical School, Southeast University , Nanjing , China , and.
Yu Y
a Key Laboratory of Environmental Medicine Engineering in Ministry of Education, Medical School, Southeast University , Nanjing , China , and.
Sun Q
a Key Laboratory of Environmental Medicine Engineering in Ministry of Education, Medical School, Southeast University , Nanjing , China , and.
Wang D
a Key Laboratory of Environmental Medicine Engineering in Ministry of Education, Medical School, Southeast University , Nanjing , China , and.

MeSH

AnimalsCaenorhabditis elegansCaenorhabditis elegans ProteinsDNA-Binding ProteinsGraphiteIntestinal MucosaIntestinesMAP Kinase Signaling SystemMitogen-Activated Protein Kinase 1NF-E2 Transcription FactorNanoparticlesOxidesRNA InterferenceSignal TransductionTranscription Factorsp38 Mitogen-Activated Protein Kinases

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27615004

Citation

Zhao, Yunli, et al. "P38 MAPK-SKN-1/Nrf Signaling Cascade Is Required for Intestinal Barrier Against Graphene Oxide Toxicity in Caenorhabditis Elegans." Nanotoxicology, vol. 10, no. 10, 2016, pp. 1469-1479.
Zhao Y, Zhi L, Wu Q, et al. P38 MAPK-SKN-1/Nrf signaling cascade is required for intestinal barrier against graphene oxide toxicity in Caenorhabditis elegans. Nanotoxicology. 2016;10(10):1469-1479.
Zhao, Y., Zhi, L., Wu, Q., Yu, Y., Sun, Q., & Wang, D. (2016). P38 MAPK-SKN-1/Nrf signaling cascade is required for intestinal barrier against graphene oxide toxicity in Caenorhabditis elegans. Nanotoxicology, 10(10), 1469-1479.
Zhao Y, et al. P38 MAPK-SKN-1/Nrf Signaling Cascade Is Required for Intestinal Barrier Against Graphene Oxide Toxicity in Caenorhabditis Elegans. Nanotoxicology. 2016;10(10):1469-1479. PubMed PMID: 27615004.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - p38 MAPK-SKN-1/Nrf signaling cascade is required for intestinal barrier against graphene oxide toxicity in Caenorhabditis elegans. AU - Zhao,Yunli, AU - Zhi,Lingtong, AU - Wu,Qiuli, AU - Yu,Yonglin, AU - Sun,Qiqing, AU - Wang,Dayong, Y1 - 2016/09/27/ PY - 2016/9/13/pubmed PY - 2017/6/24/medline PY - 2016/9/13/entrez KW - Caenorhabditis elegans KW - SKN-1/Nrf KW - graphene oxide KW - intestinal barrier KW - nanotoxicology KW - p38 MAPK signaling SP - 1469 EP - 1479 JF - Nanotoxicology JO - Nanotoxicology VL - 10 IS - 10 N2 - Biological barrier plays a crucial role for organisms against the possible toxicity from engineered nanomaterials (ENMs). Graphene oxide (GO) has been proven to cause potential toxicity on organisms. However, the molecular mechanisms for intestinal barrier of animals against GO toxicity are largely unclear. Using in vivo assay system of Caenorhabditis elegans, we found that mutation of genes encoding core p38 mitogen-activated protein kinase (MAPK) signaling pathway caused susceptible property to GO toxicity and enhanced translocation of GO into the body of nematodes. Genetic assays indicated that SKN-1/Nrf functioned downstream of p38 MAPK signaling pathway to regulate GO toxicity and translocation. Transcription factor of SKN-1 could regulate GO toxicity and translocation at least through function of its targeted gene of gst-4 encoding one of phase II detoxification proteins. Moreover, intestine-specific RNA interference (RNAi) assay demonstrated that the p38 MAPK-SKN-1/Nrf signaling cascade could function in intestine to regulate GO toxicity and intestinal permeability in GO exposed nematodes. Therefore, p38 MAPK-SKN-1/Nrf signaling cascade may act as an important molecular basis for intestinal barrier against GO toxicity in organisms. Exposure to GO induced significantly increased expression of genes encoding p38 MAPK-SKN-1/Nrf signaling cascade, which further implies that the identified p38 MAPK-SKN-1/Nrf signaling cascade may encode a protection mechanism for nematodes in intestine to be against GO toxicity. SN - 1743-5404 UR - https://www.unboundmedicine.com/medline/citation/27615004/p38_MAPK_SKN_1/Nrf_signaling_cascade_is_required_for_intestinal_barrier_against_graphene_oxide_toxicity_in_Caenorhabditis_elegans_ DB - PRIME DP - Unbound Medicine ER -