DOI QR코드

DOI QR Code

Methanol extract of Myelophycus caespitosus ameliorates oxidative stress-induced cytotoxicity in C2C12 murine myoblasts via activation of heme oxygenase-1

  • Cheol Park (Division of Basic Sciences, College of Liberal Studies, Dong-Eui University) ;
  • Hyun Hwangbo (Department of Biochemistry, Dong-Eui University College of Korean Medicine) ;
  • Min Ho Han (National Marine Biodiversity Institute of Korea) ;
  • Jin-Woo Jeong (Honam National Institute of Biological Resources) ;
  • Suengmok Cho (Department of Food Science and Technology, Institute of Food Science, Pukyong National University) ;
  • Gi-Young Kim (Department of Marine Life Science, Jeju National University) ;
  • Hye-Jin Hwang (Department of Food and Nutrition, College of Nursing, Healthcare Sciences & Human Ecology, Dong-Eui University) ;
  • Yung Hyun Choi (Department of Biochemistry, Dong-Eui University College of Korean Medicine)
  • Received : 2022.11.02
  • Accepted : 2022.11.15
  • Published : 2023.01.30

Abstract

Myelophycus caespitosus, a brown alga belonging to genus Myelophycus, has been traditionally used as a food and medicinal resource in Northeastern Asia. However, few studies have been conducted on its pharmacological activity. In this study, we evaluated whether methanol extract of M. caespitosus (MEMC) could protect against oxidative damage caused by hydrogen peroxide (H2O2) in C2C12 murine myoblasts. Our results revealed that MEMC could suppress H2O2-induced growth inhibition and DNA damage while blocking the production of reactive oxygen species. In H2O2-treated cells, cell cycle progression was halted at the G2/M phase, accompanied by changes in expression of key cell cycle regulators. However, these effects were attenuated by MEMC. In addition, we found that MEMC protected cells from induction of apoptosis associated with mitochondrial impairment caused by H2O2 treatment. Furthermore, MEMC enhanced the phosphorylation of nuclear factor-erythroid-2 related factor 2 (Nrf2) and expression and activity of heme oxygenase-1 (HO-1) in H2O2-treaetd C2C12 myoblasts. However, such anti-apoptotic and cytoprotective effects of MEMC were greatly abolished by HO-1 inhibitor, suggesting that MEMC could increase Nrf2-mediated activity of HO-1 to protect C2C12 myoblasts from oxidative stress.

Keywords

Acknowledgement

This research was supported by Korea Institute of Marine Science & Technology Promotion (KIMST) funded by the Ministry of Oceans and Fisheries, Korea (20220488).

References

  1. Abrigo J, Simon F, Cabrera D, Vilos C, Cabello-Verrugio C. Mitochondrial dysfunction in skeletal muscle pathologies. Curr Protein Pept Sci. 2019;20:536-46. https://doi.org/10.2174/1389203720666190402100902
  2. Besednova NN, Andryukov BG, Zaporozhets TS, Kuznetsova TA, Kryzhanovsky SP, Ermakova SP, et al. Molecular targets of brown algae phlorotannins for the therapy of inflammatory processes of various origins. Mar Drugs. 2022;20:243.
  3. Bock FJ, Tait SWG. Mitochondria as multifaceted regulators of cell death. Nat Rev Mol Cell Biol. 2020;21:85-100. https://doi.org/10.1038/s41580-019-0173-8
  4. Carroll AR, Copp BR, Davis RA, Keyzers RA, Prinsep MR. Marine natural products. Nat Prod Rep. 2021;38:362-413. https://doi.org/10.1039/D0NP00089B
  5. Choi YH. Trans-cinnamaldehyde protects C2C12 myoblasts from DNA damage, mitochondrial dysfunction and apoptosis caused by oxidative stress through inhibiting ROS production. Genes Genomics. 2021;43:303-12. https://doi.org/10.1007/s13258-020-00987-9
  6. Choi YH. Tacrolimus induces apoptosis in leukemia Jurkat cells through inactivation of the reactive oxygen species-dependent phosphoinositide-3-kinase/Akt signaling pathway. Biotechnol Bioprocess Eng. 2022;27:183-92. https://doi.org/10.1007/s12257-021-0199-6
  7. Dai Y, Jin F, Wu W, Kumar SK. Cell cycle regulation and hematologic malignancies. Blood Sci. 2019;1:34-43. https://doi.org/10.1097/BS9.0000000000000009
  8. Di Filippo ES, Mancinelli R, Pietrangelo T, La Rovere RM, Quattrocelli M, Sampaolesi M, et al. Myomir dysregulation and reactive oxygen species in aged human satellite cells. Biochem Biophys Res Commun. 2016;473:462-70. https://doi.org/10.1016/j.bbrc.2016.03.030
  9. Di Meo S, Iossa S, Venditti P. Skeletal muscle insulin resistance: role of mitochondria and other ROS sources. J Endocrinol. 2017;233:R15-42. https://doi.org/10.1530/JOE-16-0598
  10. Ding Y, Zhang Z, Yue Z, Ding L, Zhou Y, Huang Z, et al. Rosmarinic acid ameliorates H2O2-induced oxidative stress in L02 cells through MAPK and Nrf2 pathways. Rejuvenation Res. 2019;22:289-98. https://doi.org/10.1089/rej.2018.2107
  11. Drysch M, Schmidt SV, Becerikli M, Reinkemeier F, Dittfeld S, Wagner JM, et al. Myostatin deficiency protects C2C12 cells from oxidative stress by inhibiting intrinsic activation of apoptosis. Cells. 2021;10:1680.
  12. Fulle S, Sancilio S, Mancinelli R, Gatta V, Di Pietro R. Dual role of the caspase enzymes in satellite cells from aged and young subjects. Cell Death Dis. 2013;4:e955.
  13. Hanyuda T, Aoki S, Kawai H. Reinstatement of Myelophycus caespitosus (Scytosiphonaceae, Phaeophyceae) from Japan. Phycol Res. 2020;68:126-34. https://doi.org/10.1111/pre.12405
  14. Jayasooriya RGPT, Kang CH, Jang YJ, Kang SH, Dilshara MG, Choi YH, et al. Methanol extract of Myelophycus caespitosus inhibits the inflammatory response in lipopolysaccharide-stimulated BV2 microglial cells by downregulating NF-kB via Inhibition of the Akt signaling pathway. Trop J Pharm Res. 2012;11:917-24.
  15. Jayawardena TU, Asanka Sanjeewa KK, Shanura Fernando IP, Ryu BM, Kang MC, Jee Y, et al. Sargassum horneri (Turner) C. Agardh ethanol extract inhibits the fine dust inflammation response via activating Nrf2/HO-1 signaling in RAW 264.7 cells. BMC Complement Altern Med. 2018;18:249.
  16. Jenkins T, Gouge J. Nrf2 in cancer, detoxifying enzymes and cell death programs. Antioxidants. 2021;10:1030.
  17. Jeong MJ, Lim DS, Kim SO, Park C, Leem SH, Lee H, et al. Protection of oxidative stress-induced DNA damage and apoptosis by rosmarinic acid in murine myoblast C2C12 cells. Biotechnol Bioprocess Eng. 2022;27:171-82. https://doi.org/10.1007/s12257-021-0248-1
  18. Ji LL. Redox signaling in skeletal muscle: role of aging and exercise. Adv Physiol Educ. 2015;39:352-9. https://doi.org/10.1152/advan.00106.2014
  19. Kang JS, Choi IW, Han MH, Lee DS, Kim GY, Hwang HJ, et al. The cytoprotective effect of Petalonia binghamiae methanol extract against oxidative stress in C2C12 myoblasts: mediation by upregulation of heme oxygenase-1 and nuclear factor-erythroid 2 related factor 2. Mar Drugs. 2015;13:2666-79. https://doi.org/10.3390/md13052666
  20. Kopp B, Khoury L, Audebert M. Validation of the γH2AX biomarker for genotoxicity assessment: a review. Arch Toxicol. 2019;93:2103-14. https://doi.org/10.1007/s00204-019-02511-9
  21. Lekshmi VS, Rauf AA, Muraleedhara Kurup G. Sulfated polysaccharides from the edible marine algae Padina tetrastromatica attenuates isoproterenol-induced oxidative damage via activation of PI3K/Akt/Nrf2 signaling pathway: an in vitro and in vivo approach. Chem Biol Interact. 2019;308:258-68. https://doi.org/10.1016/j.cbi.2019.05.044
  22. Li J, Yang Q, Han L, Pan C, Lei C, Chen H, et al. C2C12 mouse myoblasts damage induced by oxidative stress is alleviated by the antioxidant capacity of the active substance phloretin. Front Cell Dev Biol. 2020;8:541260.
  23. Liu Y, Guo Z, Wang S, Liu Y, Wei Y. Fucoxanthin pretreatment ameliorates visible light-induced phagocytosis disruption of RPE cells under a lipid-rich environment via the Nrf2 pathway. Mar Drugs. 2021;20:15.
  24. Mubarok W, Elvitigala KCML, Nakahata M, Kojima M, Sakai S. Modulation of cell-cycle progression by hydrogen peroxide-mediated cross-linking and degradation of cell-adhesive hydrogels. Cells. 2022;11:881.
  25. Mukherjee S, Park JP, Yun JW. Carboxylesterase3 (Ces3) interacts with bone morphogenetic protein 11 and promotes differentiation of osteoblasts via Smad1/5/9 pathway. Biotechnol Bioprocess Eng. 2022;27:1-16. https://doi.org/10.1007/s12257-021-0133-y
  26. Niu T, Fu G, Zhou J, Han H, Chen J, Wu W, et al. Floridoside exhibits antioxidant properties by activating HO-1 expression via p38/ERK MAPK pathway. Mar Drugs. 2020;18:105.
  27. Park C, Hong SH, Shin SS, Lee DS, Han MH, Cha HJ, et al. Activation of the Nrf2/HO-1 signaling pathway contributes to the protective effects of Sargassum serratifolium extract against oxidative stress-induced DNA damage and apoptosis in SW1353 human chondrocytes. Int J Environ Res Public Health. 2018;15:1173.
  28. Park C, Lee H, Hong S, Molagoda IMN, Jeong JW, Jin CY, et al. Inhibition of lipopolysaccharide-induced inflammatory and oxidative responses by trans-cinnamaldehyde in C2C12 myoblasts. Int J Med Sci. 2021;18:2480-92. https://doi.org/10.7150/ijms.59169
  29. Pradhan B, Nayak R, Patra S, Jit BP, Ragusa A, Jena M. Bioactive metabolites from marine algae as potent pharmacophores against oxidative stress-associated human diseases: a comprehensive review. Molecules. 2020;26:37.
  30. Rahmanian N, Shokrzadeh M, Eskandani M. Recent advances in γH2AX biomarker-based genotoxicity assays: a marker of DNA damage and repair. DNA Repair (Amst). 2021;108:103243.
  31. Rui Y, Li S, Luan F, Li D, Liu R, Zeng N. Several alkaloids in Chinese herbal medicine exert protection in acute kidney injury: focus on mechanism and target analysis. Oxid Med Cell Longev. 2022;2022:2427802.
  32. Sambasivan R, Tajbakhsh S. Adult skeletal muscle stem cells. Results Probl Cell Differ. 2015;56:191-213. https://doi.org/10.1007/978-3-662-44608-9_9
  33. Santa-Gonzalez GA, Gomez-Molina A, Arcos-Burgos M, Meyer JN, Camargo M. Distinctive adaptive response to repeated exposure to hydrogen peroxide associated with upregulation of DNA repair genes and cell cycle arrest. Redox Biol. 2016;9:124-33. https://doi.org/10.1016/j.redox.2016.07.004
  34. Sarwar MS, Xia YX, Liang ZM, Tsang SW, Zhang HJ. Mechanistic pathways and molecular targets of plant-derived anticancer ent-kaurane diterpenes. Biomolecules. 2020;10:144.
  35. Sivandzade F, Bhalerao A, Cucullo L. Analysis of the mitochondrial membrane potential using the cationic JC-1 dye as a sensitive fluorescent probe. Bio Protoc. 2019;9:e3128.
  36. Song BR, Alam MB, Lee SH. Terpenoid-rich extract of Dillenia indica L. bark displays antidiabetic action in insulin-resistant C2C12 cells and STZ-induced diabetic mice by attenuation of oxidative stress. Antioxidants (Basel). 2022;11:1227.
  37. Steinbacher P, Eckl P. Impact of oxidative stress on exercising skeletal muscle. Biomolecules. 2015;5:356-77. https://doi.org/10.3390/biom5020356
  38. Taylor WR, Stark GR. Regulation of the G2/M transition by p53. Oncogene. 2001;20:1803-15. https://doi.org/10.1038/sj.onc.1204252
  39. Tiwari S, Dewry RK, Srivastava R, Nath S, Mohanty TK. Targeted antioxidant delivery modulates mitochondrial functions, ameliorates oxidative stress and preserve sperm quality during cryopreservation. Theriogenology. 2022;179:22-31. https://doi.org/10.1016/j.theriogenology.2021.11.013
  40. Tonelli C, Chio IIC, Tuveson DA. Transcriptional regulation by Nrf2. Antioxid Redox Signal. 2018;29:1727-45. https://doi.org/10.1089/ars.2017.7342
  41. Urbani A, Prosdocimi E, Carrer A, Checchetto V, Szabo I. Mitochondrial ion channels of the inner membrane and their regulation in cell death signaling. Front Cell Dev Biol. 2021;8:620081.
  42. Wu AG, Yong YY, Pan YR, Zhang L, Wu JM, Zhang Y, et al. Targeting Nrf2-mediated oxidative stress response in traumatic brain injury: therapeutic perspectives of phytochemicals. Oxid Med Cell Longev. 2022;2022:1015791.
  43. Xu W, Zhu H, Hu B, Cheng Y, Guo Y, Yao W, et al. Echinacea in hepatopathy: a review of its phytochemistry, pharmacology, and safety. Phytomedicine. 2021;87:153572.
  44. Yu LM, Zhang WH, Han XX, Li YY, Lu Y, Pan J, et al. Hypoxia-induced ROS contribute to myoblast pyroptosis during obstructive sleep apnea via the NF-κB/HIF-1α signaling pathway. Oxid Med Cell Longev. 2019;2019:4596368.
  45. Yu Y, Cui Y, Niedernhofer LJ, Wang Y. Occurrence, biological consequences, and human health relevance of oxidative stress-induced DNA damage. Chem Res Toxicol. 2016;29:2008-39. https://doi.org/10.1021/acs.chemrestox.6b00265
  46. Yu ZY, Ma D, He ZC, Liu P, Huang J, Fang Q, et al. Heme oxygenase-1 protects bone marrow mesenchymal stem cells from iron overload through decreasing reactive oxygen species and promoting IL-10 generation. Exp Cell Res. 2018;362:28-42. https://doi.org/10.1016/j.yexcr.2017.10.029
  47. Zhang Q, Liu J, Duan H, Li R, Peng W, Wu C. Activation of Nrf2/HO-1 signaling: an important molecular mechanism of herbal medicine in the treatment of atherosclerosis via the protection of vascular endothelial cells from oxidative stress. J Adv Res. 2021;34:43-63. https://doi.org/10.1016/j.jare.2021.06.023