Identification and Characterization of a Novel Gene-encoded Antioxidant Peptide from Odorous Frog Skin

Author(s): Xiaoqing Cao, Jing Tang, Zhe Fu, Zhuo Feng, Siyuan Wang, Meifeng Yang, Chunyun Wu, Ying Wang*, Xinwang Yang*.

Journal Name: Protein & Peptide Letters

Volume 26 , Issue 3 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Amphibian skin plays an essential role in protecting organisms from harmful external factors such as UV radiation. How amphibians protect themselves from reactive oxygen species following long-term sun exposure is an important and interesting question. Amphibian skins possess a novel antioxidant system composed of various Antioxidant Peptides (AOPs), which maintain redox homeostasis. However, only a few AOPs have been identified so far.

Methods: Using combinational methods of peptidomics and genomics, we characterized a novel gene-encoded antioxidant peptide (herein named OA-VI12) from Odorrana andersonii skin secretions, which was produced by the post-translational processing of a 59-residue prepropeptide. The amino acid sequence of the OA-V112 was 'VIPFLACRPLGL', with a molecular mass of 1298.6 Da and no observed post-transcriptional modifications. Functional analysis demonstrated that OA-VI12 was capable of scavenging ABTS+, DPPH, NO and decreasing the Fe3+ production.

Results: We determined that the C7 amino acid was responsible for ABTS+ and Fe3+ scavenging, activities, the F4, C7, and P9 amino acids were crucial for DPPH scavenging activity, and the P9 amino acid was responsible for NO scavenging activity. Unlike several other amphibian peptides, OA-VI12 did not accelerate wound healing in a full-thickness skin-wound mouse model and did not demonstrate direct microbial killing. Here, we identified and named a novel gene-encoded antioxidant peptide from the skin secretions of an odorous frog species, which may assist in the development of potential antioxidant candidates.

Conclusion: This study may help improve our understanding of the molecular basis of amphibians’ adaptation to environments experiencing long-term UV radiation.

Keywords: Odorrana andersonii, OA-VI12, antioxidant peptide, molecular basis, amphibian adaptation, UV radiation.

[1]
Lalhminghlui, K.; Jagetia, G.C. Evaluation of the free-radical scavenging and antioxidant activities of Chilauni Schima wallichii Korth in vitro. Future Sci, 2018, 4(2), FSO272.
[2]
Shang, H.M.; Zhou, H.Z.; Yang, J.Y.; Li, R.; Song, H.; Wu, H.X. In vitro and in vivo antioxidant activities of inulin. PLoS One, 2018, 13(2), e0192273.
[3]
Baur, J.A.; Pearson, K.J.; Price, N.L.; Jamieson, H.A.; Lerin, C.; Kalra, A.; Prabhu, V.V.; Allard, J.S.; Lopez-Lluch, G.; Lewis, K.; Pistell, P.J.; Poosala, S.; Becker, K.G.; Boss, O.; Gwinn, D.; Wang, M.; Ramaswamy, S.; Fishbein, K.W.; Spencer, R.G.; Lakatta, E.G.; Le Couteur, D.; Shaw, R.J.; Navas, P.; Puigserver, P.; Ingram, D.K.; de Cabo, R.; Sinclair, D.A. Resveratrol improves health and survival of mice on a high-calorie diet. Nature, 2006, 444(7117), 337-342.
[4]
Calabrese, V.; Maines, M.D. Antiaging medicine: antioxidants and aging. Antioxid. Redox Signal., 2006, 8(3-4), 362-364.
[5]
Pryor, W.A. Free radical biology: Xenobiotics, cancer, and aging. Ann. N. Y. Acad. Sci., 1982, 393, 1-22.
[6]
Barbosa, E.A.; Oliveira, A.; Placido, A.; Socodato, R.; Portugal, C.C.; Mafud, A.C.; Ombredane, A.S.; Moreira, D.C.; Vale, N.; Bessa, L.J.; Joanitti, G.A.; Alves, C.; Gomes, P.; Delerue-Matos, C.; Mascarenhas, Y.P.; Marani, M.M.; Relvas, J.B.; Pintado, M.; Leite, J. Structure and function of a novel antioxidant peptide from the skin of tropical frogs. Free Radic. Biol. Med., 2018, 115, 68-79.
[7]
Yang, X.; Wang, Y.; Zhang, Y.; Lee, W.H.; Zhang, Y. Rich diversity and potency of skin antioxidant peptides revealed a novel molecular basis for high-altitude adaptation of amphibians. Sci. Rep., 2016, 6, 19866.
[8]
Cao, X.; Wang, Y.; Wu, C.; Li, X.; Fu, Z.; Yang, M.; Bian, W.; Wang, S.; Song, Y.; Tang, J.; Yang, X. Cathelicidin-OA1, a novel antioxidant peptide identified from an amphibian, accelerates skin wound healing. Sci. Rep., 2018, 8(1), 943.
[9]
Yu, H.; Qiao, X.; Gao, J.; Wang, C.; Cai, S.; Feng, L.; Wang, H.; Wang, Y.P. Identification and characterization of novel antioxidant peptides involved in redox homeostasis of frog, Limnonectes fragilis. Protein Pept. Lett., 2015, 22(9), 776-784.
[10]
Brogden, K.A. Antimicrobial peptides: Pore formers or metabolic inhibitors in bacteria? Nat. Rev. Microbiol., 2005, 3(3), 238-250.
[11]
Clarke, B.T. The natural history of amphibian skin secretions, their normal functioning and potential medical applications. Biol. Rev. Camb. Philos. Soc., 1997, 72(3), 365-379.
[12]
Li, J.; Xu, X.; Xu, C.; Zhou, W.; Zhang, K.; Yu, H.; Zhang, Y.; Zheng, Y.; Rees, H.H.; Lai, R.; Yang, D.; Wu, J. Anti-infection peptidomics of amphibian skin. Mol. Cell. Proteomics, 2007, 6(5), 882-894.
[13]
Simmaco, M.; De Biase, D.; Severini, C.; Aita, M.; Erspamer, G.F.; Barra, D.; Bossa, F. Purification and characterization of bioactive peptides from skin extracts of Rana esculenta. Biochim. Biophys. Acta, 1990, 1033(3), 318-323.
[14]
Duda, T.F. Jr.; Vanhoye, D.; Nicolas, P. Roles of diversifying selection and coordinated evolution in the evolution of amphibian antimicrobial peptides. Mol. Biol. Evol., 2002, 19(6), 858-864.
[15]
Yang, H.; Wang, X.; Liu, X.; Wu, J.; Liu, C.; Gong, W.; Zhao, Z.; Hong, J.; Lin, D.; Wang, Y.; Lai, R. Antioxidant peptidomics reveals novel skin antioxidant system. Mol. Cell. Proteomics, 2009, 8(3), 571-583.
[16]
Guo, C.; Hu, Y.; Li, J.; Liu, Y.; Li, S.; Yan, K.; Wang, X.; Liu, J.; Wang, H. Identification of multiple peptides with antioxidant and antimicrobial activities from skin and its secretions of Hylarana taipehensis, Amolops lifanensis, and Amolops granulosus. Biochimie, 2014, 105, 192-201.
[17]
Liu, C.; Hong, J.; Yang, H.; Wu, J.; Ma, D.; Li, D.; Lin, D.; Lai, R. Frog skins keep redox homeostasis by antioxidant peptides with rapid radical scavenging ability. Free Radic. Biol. Med., 2010, 48(9), 1173-1181.
[18]
He, W.; Feng, F.; Huang, Y.; Guo, H.; Zhang, S.; Li, Z.; Liu, J.; Wang, Y.; Yu, H. Host defense peptides in skin secretions of Odorrana tiannanensis: Proof for other survival strategy of the frog than merely anti-microbial. Biochimie, 2012, 94(3), 649-655.
[19]
Lu, Z.; Zhai, L.; Wang, H.; Che, Q.; Wang, D.; Feng, F.; Zhao, Z.; Yu, H. Novel families of antimicrobial peptides with multiple functions from skin of Xizang plateau frog Nanorana parkeri. Biochimie, 2010, 92(5), 475-481.
[20]
Xu, X.; Lai, R. The chemistry and biological activities of peptides from amphibian skin secretions. Chem. Rev., 2015, 115(4), 1760-1846.
[21]
Kohen, R.; Gati, I. Skin low molecular weight antioxidants and their role in aging and in oxidative stress. Toxicology, 2000, 148(2-3), 149-157.
[22]
Shindo, Y.; Witt, E.; Packer, L. Antioxidant defense mechanisms in murine epidermis and dermis and their responses to ultraviolet light. J. Invest. Dermatol., 1993, 100(3), 260-265.
[23]
Kohen, R. Skin antioxidants: Their role in aging and in oxidative stress--new approaches for their evaluation. Biomed. Pharmacother., 1999, 53(4), 181-192.
[24]
Iwaya, C.; Nomiyama, T.; Komatsu, S.; Kawanami, T.; Tsutsumi, Y.; Hamaguchi, Y.; Horikawa, T.; Yoshinaga, Y.; Yamashita, S.; Tanaka, T.; Terawaki, Y.; Tanabe, M.; Nabeshima, K.; Iwasaki, A.; Yanase, T. Exendin-4, a glucagonlike peptide-1 receptor agonist, attenuates breast cancer growth by inhibiting NF-kappaB activation. Endocrinology, 2017, 158(12), 4218-4232.
[25]
Rose, R.C.; Bode, A.M. Biology of free radical scavengers: An evaluation of ascorbate. FASEB J., 1993, 7(12), 1135-1142.
[26]
Barbosa, E.A.; Iembo, T.; Martins, G.R.; Silva, L.P.; Prates, M.V.; Andrade, A.C.; Bloch, C., Jr Skin secretion peptides: The molecular facet of the deimatic behavior of the four-eyed frog, Physalaemus nattereri (Anura, Leptodactylidae). Rapid Commun. Mass Spectrom., 2015, 29(21), 2061-2068.
[27]
Lai, R.; Liu, H.; Lee, H. W.; Zhang, Y. A novel bradykinin-related peptide from skin secretions of toad Bombina maxima and its precursor containing six identical copies of the final product. Biochem. Biophys. Res. Commun., 2001, 286(2), 259-263.
[28]
Stocker, R. Antioxidant activities of bile pigments. Antioxid. Redox Signal., 2004, 6(5), 841-849.


Rights & PermissionsPrintExport Cite as


Article Details

VOLUME: 26
ISSUE: 3
Year: 2019
Page: [160 - 169]
Pages: 10
DOI: 10.2174/0929866525666181114153136
Price: $58

Article Metrics

PDF: 16
HTML: 2