Photoprotective and therapeutic effects of Apamin, Melittin and Phospholipase A2 on human keratinocyte cell line

Year 2022, Volume: 50 Issue: 1, 13 - 24, 05.01.2022

Esin Akbay , Alp Yiğit Özdemir , Şebnem Erfen , Mehmet Ali Onur

https://doi.org/10.15671/hjbc.901013

Abstract

The aim of this study is to determine the protective and therapeutic properties of bee venom components Apamin, Melittin and Phospholipase A2 against UV damage on the human keratinocyte cell line. Cosmetic and therapeutic effects of bee venom have been reported in previous studies, but it is not known which components of the venom have the most effect. For this purpose, firstly, an in vitro UV damage model was designed. Components of bee venom were tested at a different concentration. Cell viability, cytotoxicity and apoptotic processes were analyzed on the designed model. As a result, it has been observed that Apamin demonstrated a significant protective effect against UV-induced cell death at all concentrations. Photoprotective effects of Melittin were observed in all concentration time periods and its photoprotective effects were increased as the concentration increased. Our results were indicated that Phospholipase A2 could be used as a photoprotective and phototherapy agent. This study is the first to show the protective and therapeutic properties of bee venom components against UV damage. As a result, it has been shown that these components can be successful photoprotective and phototherapeutic agents against UV-induced damage, but more detailed studies should be conducted to minimize their toxic effects on cells.

Keywords

Apamin, Melittin, Phospholipase A2, Photoprotection, Phototherapy, HaCaT cell line

Project Number

FHD-2020-18650

References

• Referans1 M.T. Leccia, C. Lebbe, J.P. Claudel, M. Narda, N. Basset-Seguin, New Vision in Photoprotection and Photorepair, Dermatol. Ther., 9 (2019) 103-115.
• Referans2 N. Sánchez-Marzo, A. Pérez-Sánchez, V. Ruiz-Torres, A. Martínez-Tébar, J. Castillo, M. Herranz-López, E. Barrajón-Catalán, Antioxidant and Photoprotective Activity of Apigenin and its Potassium Salt Derivative in Human Keratinocytes and Absorption in Caco-2 Cell Monolayers, Int. J. Mol. Sci., 20 (2019) 2148.
• Referans3 M. Wlaschek, G. Heinen, A. Poswig, A. Schwarz, T. Krieg, K. Scharffetter-Kochanek, UVA-induced autocrine stimulation of fibroblast-derived collagenase/MMP-1 by interrelated loops of interleukin-1 and interleukin-6, Photochem. Photobiol., 59 (1994) 550-556.
• Referans4 M. Ichihashi, M. Ueda, A. Budiyanto, T. Bito, M. Oka, M. Fukunaga, K. Tsuru, T. Horikawa, UV-induced skin damage, Toxicology, 189 (2003) 21-39.
• Referans5 C.S. Sander, H. Changi, F. Hamm, P. Elsner, J.J. Thiele, Role of oxidative stress and the antioxidant network in cutaneous carcinogenesis, Int. J. Dermatol., 43 (2004) 326-335.
• Referans6 A. Kurek-Górecka, M. Górecki, A. Rzepecka-Stojko, R. Balwierz, J. Stojko, Bee Products in Dermatology and Skin Care, Molecules, 25 (2020) 556.
• Referans7 R. Wehbe, J. Frangieh, M. Rima, D. El Obeid, J.M. Sabatier, Z. Fajloun, Bee Venom: Overview of Main Compounds and Bioactivities for Therapeutic Interests, Molecules, 24 (2019) 2997.
• Referans8 C. Lamy, S.J. Goodchild, K.L. Weatherall, D.E. Jane, J.F. Liégeois, V. Seutin, N.V. Marrion, Allosteric block of KCa2 channels by apamin, J. Biol. Chem., 285 (2010) 27067-27077.
• Referans9 M. Moreno, E. Giralt, Three valuable peptides from bee and wasp venoms for therapeutic and biotechnological use: melittin, apamin and mastoparan, Toxins (Basel), 7 (2015) 1126-1150.
• Referans10 W.H. Kim, H.J. An, J.Y. Kim, M.G. Gwon, H. Gu, S.J. Lee, J.Y. Park, K.D. Park, S.M. Han, M.K. Kim, K.K. Park, Apamin inhibits TNF-α- and IFN-γ-induced inflammatory cytokines and chemokines via suppressions of NF-κB signaling pathway and STAT in human keratinocytes, Pharmacol. Rep., 69 (2017) 1030-1035.
• Referans11 A.B. Mukherjee, L. Miele, N. Pattabiraman, Phospholipase A2 enzymes: regulation and physiological role, Biochem Pharmacol., 48 (1994) 1-10.
• Referans 12 G.A. Scott, S.E. Jacobs, A.P. Pentland, sPLA2-X stimulates cutaneous melanocyte dendricity and pigmentation through a lysophosphatidylcholine-dependent mechanism, J. Invest. Dermatol. 126 (2006) 855-861.
• Referans13 V. Muthusamy, T.J. Piva, A comparative study of UV-induced cell signalling pathways in human keratinocyte-derived cell lines, Arch. Dermatol. Res., 305 (2013) 817-833.
• Referans14 S. Han, K. Lee, J. Yeo, H. Kweon, S. Woo, M. Lee, H. Baek, K. Park, Inhibitory effect of bee venom against ultraviolet B induced MMP-11 and MMP-3 in human dermal fibroblasts, J. Apicult. Res., 46 (2007) 94-98.
• Referans15 H.J. An, J.Y. Kim, W.H. Kim, M.G Gwon, H.M. Gu, M.J. Jeon, S.M. Han, S.C. Pak, C.K. Lee, I.S. Park, K.K. Park, Therapeutic effects of bee venom and its major component, melittin, on atopic dermatitis in vivo and in vitro, Br. J. Pharmacol., 175 (2018) 4310-4324.
• Referans16 A. Nakashima, S. Tomono, T. Yamazaki, M. Inui, N. Morita, I. Ichimonji, H. Takagi, F. Nagaoka, M. Matsumoto, Y. Ito, T. Yanagishita, K. Miyake, D. Watanabe, S. Akashi-Takamura, Phospholipase A2 from bee venom increases poly(I:C)-induced activation in human keratinocytes, Int. Immunol., 32 (2020) 371-383.
• Referans17 K.P. Lawrence, R. Gacesa, P.F. Long, A.R. Young, Molecular photoprotection of human keratinocytes in vitro by the naturally occurring mycosporine-like amino acid palythine, Br. J. Dermatol., 178 (2018) 1353-1363.
• Referans18 L. Li, M. Li, S. Xu, H. Chen, X. Chen, H. Gu, Apigenin restores impairment of autophagy and downregulation of unfolded protein response regulatory proteins in keratinocytes exposed to ultraviolet B radiation, J. Photochem. Photobiol. B., 194 (2019) 84-95.
• Referans19 A.B. Durukan, E. Akbay, A. Ünlü, A. Özdemir, M.A. Onur, The cytotoxic properties and apoptotic potential of N-butyl and 2-octyl cyanoacrylates used in surgical treatment of chronic venous insufficiency, Turk Gogus Kalp Damar Cerrahisi Derg., 27 (2019) 185-191.
• Referans20 S.I. Abdel Wahab, A.B. Abdul, A.S. Alzubairi, M. Mohamed Elhassan, S. Mohan, In vitro ultramorphological assessment of apoptosis induced by zerumbone on (HeLa), J. Biomed. Biotechnol., 2009 (2009) 769568.
• Referans21 G. Ciapetti, D. Granchi, L. Savarino, E. Cenni, E. Magrini, N. Baldini, A. Giunti, In vitro testing of the potential for orthopedic bone cements to cause apoptosis of osteoblast-like cells, Biomaterials, 23 (2002) 617-627.
• Referans22 S.M. Han, G.G. Lee, K.K. Park, Skin Sensitization Study of Bee Venom (Apis mellifera L.) in Guinea Pigs, Toxicol. Res., 28 (2012) 1-4.
• Referans23 S.M. Han, I.P. Hong, S.O. Woo, S.N. Chun, K.K. Park, Y.M. Nicholls, S.C. Pak, The beneficial effects of honeybee-venom serum on facial wrinkles in humans, Clin. Interv. Aging, 10 (2015) 1587-1592.
• Referans24 S.M. Han, I.P. Hong, S.O. Woo, S.G. Kim, H.R. Jang, K.K. Park, Evaluation of the skin phototoxicity and photosensitivity of honeybee venom, J. Cosmet. Dermatol., 16 (2017) e68-e75.
• Referans25 M. Lazdunski, M. Fosset, M. Hughes, C. Mourre, G. Romey, H. Schmid-Antomarchi, The apamin-sensitive Ca2+-dependent K+ channel molecular properties, differentiation and endogenous ligands in mammalian brain, Biochem. Soc. Symp., 50 (1985) 31-42.
• Referans26 H. Raghuraman, A. Chattopadhyay, Melittin: a membrane-active peptide with diverse functions, Biosci. Rep. ,27 (2007) 189-223.
• Referans27 W.R. Lee, K.H. Kim, H.J. An, J.Y. Kim, Y.C. Chang, H. Chung, Y.Y. Park, M.L. Lee, K.K. Park, The protective effects of melittin on Propionibacterium acnes-induced inflammatory responses in vitro and in vivo, J. Invest. Dermatol., 134 (2014)1922-1930.
• Referans28 W.H. Kim, H.J. An, J.Y. Kim, M.G. Gwon, H. Gu, M. Jeon, M.K. Kim, S.M. Han, K.K. Park, Anti-Inflammatory Effect of Melittin on Porphyromonas Gingivalis LPS-Stimulated Human Keratinocytes, Molecules, 23 (2018) 332.
• Referans29 D.J. Son, J.W. Lee, Y.H. Lee, H.S. Song, C.K. Lee, J.T. Hong, Therapeutic application of anti-arthritis, pain-releasing, and anti-cancer effects of bee venom and its constituent compounds, Pharmacol. Ther., 115 (2007) 246-270.
• Referans30 A.K. Sobotka, R.M. Franklin, N.F. Adkinson, M. Valentine, H. Baer, L.M. Lichtenstein, Allergy to insect stings. II. Phospholipase A: the major allergen in honeybee venom, J. Allergy Clin. Immunol., 57 (1976) 29-40.
• Referans31 N.W. Palm, R.K. Rosenstein, S. Yu, D.D. Schenten, E. Florsheim, R. Medzhitov, Bee venom phospholipase A2 induces a primary type 2 response that is dependent on the receptor ST2 and confers protective immunity, Immunity, 39 (2013) 976-985.