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Phytochemicals-induced hormesis protects Caenorhabditis elegans against α-synuclein protein aggregation and stress through modulating HSF-1 and SKN-1/Nrf2 signaling pathways.
Biomed Pharmacother. 2018 Jun; 102:812-822.BP

Abstract

Mild stress activates the adaptive cellular response for the subsequent severe stress called hormesis. Hormetic stress plays a vital role to activate multiple stress-responsive genes for the benefit of an organism. In tropical regions of world, tubers of Dioscorea spp. has been extensively used in folk medicine and also consumed as food. In this study, we report that the phytochemicals of Dioscorea alata L., tubers extends the lifespan of nematode model Caenorhabditis elegans by hormetic mechanism. We showed that the low dose of tubers extract at 200 and 300 μg/mL extends the mean lifespan of wild-type worms, whereas higher doses are found to be toxic. Supplementation of tubers extract slightly increased the intracellular ROS in second-day adult worms and it might activate the adaptive stress response, which protects the worms from oxidative and thermal stress. Transgenic reporter gene expression assay showed that extract treatment enhanced the expression of stress protective genes such as hsp-16.2, hsp-6, hsp-60 and gst-4. Further studies proved that the transcription factors HSF-1 and SKN-1/Nrf2 were implicated in hormetic stress response of the worms. Moreover, pretreatment of extract reduced the high glucose-mediated lipid accumulation by enhancing the expression of glyoxalase-1. It was also found that the aggregation of Parkinson's related protein α-synuclein reduced in the transgenic strain NL5901 and extended its lifespan. Finally, our results concluded that the presences of hormetic dietary phytochemicals in tubers might drive the stress response in C. elegans via HSF-1 and SKN-1/Nrf2 signaling pathways.

Authors+Show Affiliations

Unit of Nematology, Department of Zoology, Bharathiar University, Coimbatore, Tamil Nadu, India.Unit of Nematology, Department of Zoology, Bharathiar University, Coimbatore, Tamil Nadu, India.Unit of Nematology, Department of Zoology, Bharathiar University, Coimbatore, Tamil Nadu, India.Unit of Nematology, Department of Zoology, Bharathiar University, Coimbatore, Tamil Nadu, India.College of Science, Northeastern University, Boston, MA 02115, USA.Unit of Nematology, Department of Zoology, Bharathiar University, Coimbatore, Tamil Nadu, India. Electronic address: sunpalan@gmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29605769

Citation

Govindan, Shanmugam, et al. "Phytochemicals-induced Hormesis Protects Caenorhabditis Elegans Against Α-synuclein Protein Aggregation and Stress Through Modulating HSF-1 and SKN-1/Nrf2 Signaling Pathways." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 102, 2018, pp. 812-822.
Govindan S, Amirthalingam M, Duraisamy K, et al. Phytochemicals-induced hormesis protects Caenorhabditis elegans against α-synuclein protein aggregation and stress through modulating HSF-1 and SKN-1/Nrf2 signaling pathways. Biomed Pharmacother. 2018;102:812-822.
Govindan, S., Amirthalingam, M., Duraisamy, K., Govindhan, T., Sundararaj, N., & Palanisamy, S. (2018). Phytochemicals-induced hormesis protects Caenorhabditis elegans against α-synuclein protein aggregation and stress through modulating HSF-1 and SKN-1/Nrf2 signaling pathways. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 102, 812-822. https://doi.org/10.1016/j.biopha.2018.03.128
Govindan S, et al. Phytochemicals-induced Hormesis Protects Caenorhabditis Elegans Against Α-synuclein Protein Aggregation and Stress Through Modulating HSF-1 and SKN-1/Nrf2 Signaling Pathways. Biomed Pharmacother. 2018;102:812-822. PubMed PMID: 29605769.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phytochemicals-induced hormesis protects Caenorhabditis elegans against α-synuclein protein aggregation and stress through modulating HSF-1 and SKN-1/Nrf2 signaling pathways. AU - Govindan,Shanmugam, AU - Amirthalingam,Mohankumar, AU - Duraisamy,Kalaiselvi, AU - Govindhan,Thiruppathi, AU - Sundararaj,Nivitha, AU - Palanisamy,Sundararaj, Y1 - 2018/04/05/ PY - 2017/12/11/received PY - 2018/03/21/revised PY - 2018/03/22/accepted PY - 2018/4/2/pubmed PY - 2018/10/3/medline PY - 2018/4/2/entrez KW - Caenorhabditis elegans KW - Dioscorea alata KW - Glyoxalase-1 KW - HSF-1 KW - Hormesis KW - SKN-1/Nrf2 SP - 812 EP - 822 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed. Pharmacother. VL - 102 N2 - Mild stress activates the adaptive cellular response for the subsequent severe stress called hormesis. Hormetic stress plays a vital role to activate multiple stress-responsive genes for the benefit of an organism. In tropical regions of world, tubers of Dioscorea spp. has been extensively used in folk medicine and also consumed as food. In this study, we report that the phytochemicals of Dioscorea alata L., tubers extends the lifespan of nematode model Caenorhabditis elegans by hormetic mechanism. We showed that the low dose of tubers extract at 200 and 300 μg/mL extends the mean lifespan of wild-type worms, whereas higher doses are found to be toxic. Supplementation of tubers extract slightly increased the intracellular ROS in second-day adult worms and it might activate the adaptive stress response, which protects the worms from oxidative and thermal stress. Transgenic reporter gene expression assay showed that extract treatment enhanced the expression of stress protective genes such as hsp-16.2, hsp-6, hsp-60 and gst-4. Further studies proved that the transcription factors HSF-1 and SKN-1/Nrf2 were implicated in hormetic stress response of the worms. Moreover, pretreatment of extract reduced the high glucose-mediated lipid accumulation by enhancing the expression of glyoxalase-1. It was also found that the aggregation of Parkinson's related protein α-synuclein reduced in the transgenic strain NL5901 and extended its lifespan. Finally, our results concluded that the presences of hormetic dietary phytochemicals in tubers might drive the stress response in C. elegans via HSF-1 and SKN-1/Nrf2 signaling pathways. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/29605769/Phytochemicals_induced_hormesis_protects_Caenorhabditis_elegans_against_α_synuclein_protein_aggregation_and_stress_through_modulating_HSF_1_and_SKN_1/Nrf2_signaling_pathways_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(17)36784-7 DB - PRIME DP - Unbound Medicine ER -