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Novel Bioactive Peptides from Meretrix meretrix Protect Caenorhabditis elegans against Free Radical-Induced Oxidative Stress through the Stress Response Factor DAF-16/FOXO.
Mar Drugs 2018; 16(11)MD

Abstract

The hard clam Meretrix meretrix, which has been traditionally used as medicine and seafood, was used in this study to isolate antioxidant peptides. First, a peptide-rich extract was tested for its protective effect against paraquat-induced oxidative stress using the nematode model Caenorhabditis elegans. Then, three novel antioxidant peptides; MmP4 (LSDRLEETGGASS), MmP11 (KEGCREPETEKGHR) and MmP19 (IVTNWDDMEK), were identified and were found to increase the resistance of nematodes against paraquat. Circular dichroism spectroscopy revealed that MmP4 was predominantly in beta-sheet conformation, while MmP11 and MmP19 were primarily in random coil conformation. Using transgenic nematode models, the peptides were shown to promote nuclear translocation of the DAF-16/FOXO transcription factor, a pivotal regulator of stress response and lifespan, and induce the expression of superoxide dismutase 3 (SOD-3), an antioxidant enzyme. Analysis of DAF-16 target genes by real-time PCR reveals that sod-3 was up-regulated by MmP4, MmP11 and MmP19 while ctl-1 and ctl-2 were also up-regulated by MmP4. Further examination of daf-16 using RNA interference suggests that the peptide-increased resistance of C. elegans to oxidative stress was DAF-16 dependent. Taken together, these data demonstrate the antioxidant activity of M. meretrix peptides, which are associated with activation of the stress response factor DAF-16 and regulation of the antioxidant enzyme genes.

Authors+Show Affiliations

Center for Bioresources and Drug Discovery, School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China. jiawzh@gdpu.edu.cn.Center for Bioresources and Drug Discovery, School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China. pengqbetter@163.com.Center for Bioresources and Drug Discovery, School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China. sulinnan1234@foxmail.com.Center for Bioresources and Drug Discovery, School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China. axuesong@163.com.Research and Development Center, Infinitus (China) Company Ltd., Guangzhou 510665, China. william.ma@infinitus-int.com.Research and Development Center, Infinitus (China) Company Ltd., Guangzhou 510665, China. fiona.liang@infinitus-int.com.Research and Development Center, Infinitus (China) Company Ltd., Guangzhou 510665, China. xiquan.yin@infinitus-int.com.Shenzhen Key Laboratory of Microbiology and Gene Engineering, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China. zouyd@szu.edu.cn.Center for Bioresources and Drug Discovery, School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China. huangzebo@scut.edu.cn. School of Food Science and Engineering, South China University of Technology, Guangzhou 510641, China. huangzebo@scut.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30423886

Citation

Jia, Weizhang, et al. "Novel Bioactive Peptides From Meretrix Meretrix Protect Caenorhabditis Elegans Against Free Radical-Induced Oxidative Stress Through the Stress Response Factor DAF-16/FOXO." Marine Drugs, vol. 16, no. 11, 2018.
Jia W, Peng Q, Su L, et al. Novel Bioactive Peptides from Meretrix meretrix Protect Caenorhabditis elegans against Free Radical-Induced Oxidative Stress through the Stress Response Factor DAF-16/FOXO. Mar Drugs. 2018;16(11).
Jia, W., Peng, Q., Su, L., Yu, X., Ma, C. W., Liang, M., ... Huang, Z. (2018). Novel Bioactive Peptides from Meretrix meretrix Protect Caenorhabditis elegans against Free Radical-Induced Oxidative Stress through the Stress Response Factor DAF-16/FOXO. Marine Drugs, 16(11), doi:10.3390/md16110444.
Jia W, et al. Novel Bioactive Peptides From Meretrix Meretrix Protect Caenorhabditis Elegans Against Free Radical-Induced Oxidative Stress Through the Stress Response Factor DAF-16/FOXO. Mar Drugs. 2018 Nov 11;16(11) PubMed PMID: 30423886.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel Bioactive Peptides from Meretrix meretrix Protect Caenorhabditis elegans against Free Radical-Induced Oxidative Stress through the Stress Response Factor DAF-16/FOXO. AU - Jia,Weizhang, AU - Peng,Qiong, AU - Su,Linnan, AU - Yu,Xuesong, AU - Ma,Chung Wah, AU - Liang,Ming, AU - Yin,Xiquan, AU - Zou,Yongdong, AU - Huang,Zebo, Y1 - 2018/11/11/ PY - 2018/10/23/received PY - 2018/11/03/revised PY - 2018/11/06/accepted PY - 2018/11/15/entrez PY - 2018/11/15/pubmed PY - 2018/11/15/medline KW - Caenorhabditis elegans KW - Meretrix meretrix KW - antioxidant peptides KW - oxidative stress KW - reactive oxygen species KW - transcription factor DAF-16/FOXO JF - Marine drugs JO - Mar Drugs VL - 16 IS - 11 N2 - The hard clam Meretrix meretrix, which has been traditionally used as medicine and seafood, was used in this study to isolate antioxidant peptides. First, a peptide-rich extract was tested for its protective effect against paraquat-induced oxidative stress using the nematode model Caenorhabditis elegans. Then, three novel antioxidant peptides; MmP4 (LSDRLEETGGASS), MmP11 (KEGCREPETEKGHR) and MmP19 (IVTNWDDMEK), were identified and were found to increase the resistance of nematodes against paraquat. Circular dichroism spectroscopy revealed that MmP4 was predominantly in beta-sheet conformation, while MmP11 and MmP19 were primarily in random coil conformation. Using transgenic nematode models, the peptides were shown to promote nuclear translocation of the DAF-16/FOXO transcription factor, a pivotal regulator of stress response and lifespan, and induce the expression of superoxide dismutase 3 (SOD-3), an antioxidant enzyme. Analysis of DAF-16 target genes by real-time PCR reveals that sod-3 was up-regulated by MmP4, MmP11 and MmP19 while ctl-1 and ctl-2 were also up-regulated by MmP4. Further examination of daf-16 using RNA interference suggests that the peptide-increased resistance of C. elegans to oxidative stress was DAF-16 dependent. Taken together, these data demonstrate the antioxidant activity of M. meretrix peptides, which are associated with activation of the stress response factor DAF-16 and regulation of the antioxidant enzyme genes. SN - 1660-3397 UR - https://www.unboundmedicine.com/medline/citation/30423886/Novel_Bioactive_Peptides_from_Meretrix_meretrix_Protect_Caenorhabditis_elegans_against_Free_Radical_Induced_Oxidative_Stress_through_the_Stress_Response_Factor_DAF_16/FOXO_ L2 - http://www.mdpi.com/resolver?pii=md16110444 DB - PRIME DP - Unbound Medicine ER -