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Mar. Drugs 2018, 16(11), 444; https://doi.org/10.3390/md16110444

Novel Bioactive Peptides from Meretrix meretrix Protect Caenorhabditis elegans against Free Radical-Induced Oxidative Stress through the Stress Response Factor DAF-16/FOXO

1
Center for Bioresources and Drug Discovery, School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China
2
Research and Development Center, Infinitus (China) Company Ltd., Guangzhou 510665, China
3
Shenzhen Key Laboratory of Microbiology and Gene Engineering, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China
4
School of Food Science and Engineering, South China University of Technology, Guangzhou 510641, China
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 23 October 2018 / Revised: 3 November 2018 / Accepted: 6 November 2018 / Published: 11 November 2018
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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. View Full-Text
Keywords: antioxidant peptides; oxidative stress; reactive oxygen species; transcription factor DAF-16/FOXO; Meretrix meretrix; Caenorhabditis elegans antioxidant peptides; oxidative stress; reactive oxygen species; transcription factor DAF-16/FOXO; Meretrix meretrix; Caenorhabditis elegans
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Jia, W.; Peng, Q.; Su, L.; Yu, X.; Ma, C.W.; Liang, M.; Yin, X.; Zou, Y.; Huang, Z. 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, 444.

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