Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Extracts from Gracilaria vermiculophylla Prevent Cellular Senescence and Improve Differentiation Potential in Replicatively Senescent Human Bone Marrow Mesenchymal Stem Cells

홍조류인 Gracilaria vermiculophylla 추출물에 의한 노화 골수유래 중간엽줄기세포의 항노화 및 분화능력 개선 효과

  • Jeong, Sin-Gu (Department of Biology, College of Natural Science, Chosun University) ;
  • Cho, Tae Oh (Department of Biology, College of Natural Science, Chosun University) ;
  • Cho, Goang-Won (Department of Biology, College of Natural Science, Chosun University)
  • 정신구 (조선대학교 자연과학대학 생명과학과) ;
  • 조태오 (조선대학교 자연과학대학 생명과학과) ;
  • 조광원 (조선대학교 자연과학대학 생명과학과)
  • Received : 2018.05.18
  • Accepted : 2018.07.03
  • Published : 2018.09.30
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Abstract

The red algae Gracilaria vermiculophylla is widespread on seashores worldwide and has been used as food in Asian countries. Previous studies have reported that extracts of Gracilaria red algae have beneficial anti-oxidant and anti-inflammatory effects. The present study examined the anti-senescence effects of Gracilaria vermiculophylla extracts (GV-Ex) in replicatively senescent human bone marrow mesenchymal stem cells (hBM-MSCs). GV-Ex pretreatment improved the cellular viability of hBM-MSCs that had been injured by oxidative stress. These effects of GV-Ex were confirmed by MTT assay and immunoblot analysis using the apoptotic proteins p53 and cleaved caspase-3. The reactive oxygen species (ROS) levels were examined in long-term cultured Passages 17 (P-17) mesenchymal stem cells (MSC) and compared to P-7 MSC. The ROS accumulation was greater in the P-17 than in the P-7. However, these increased ROS levels in the P-17 were decreased significantly after treatment with GV-Ex, and restoration of the levels of the anti-oxidant enzymes SOD1, SOD2, and CAT was also observed under these conditions. In addition, P-17 hBM-MSC treated with GV-Ex had decreased levels of the senescence proteins p53, p21, and p16. The results show that the ability of P-17 hBM-MSC to differentiate into osteocytes and adipocytes was improved by GV-Ex treatment, suggesting that GV-Ex ameliorates the functional decline of senescent stem cells.

홍조류인 꼬물꼬시래기(Gracilaria vermiculophylla)는 전 세계의 해변 지역에 널리 퍼져 있으며 아시아 국가에서 식량 자원으로 이용되어왔다. 이전 연구에 따르면, Gracilaria 속 홍조류 추출물에서 항산화 및 항염증 효과가 보고 되었다. 본 연구에서는 노화된 인간의 골수 유래 중간엽 줄기세포(hBM-MSCs)를 이용하여 Gracilaria vermiculophylla 추출물(GV-Ex)의 항노화 효과를 조사하였다. MTT 분석와 immunoblot 분석(apoptotic protein p53과 cleaved caspase-3)을 이용하여, GV-Ex 전처리는 산화적 스트레스에 의해 손상된 hBM-MSCs의 세포생존력을 향상시킴을 확인하였다. 또, 세포내 생성된 ROS는 장기간 배양 된 MSCs (Passages 17; P-17)와 P-7 MSC에서 측정하여 서로 비교하였는데, P-17 MSC에서 증가되었고, GV-Ex 처리하면(GV-Ex treated P-17 MSCs) 유의하게 감소되었다. 또한, 항산화 효소인 SOD1와 SOD2, CAT의 발현 역시 GV-Ex 처리함에 따라 복원됨을 관찰하였다. 노화 표지단백질인 p53와 p21, p16 등의 발현 또한 GV-Ex를 처리한 P-17 MSC에서 감소되었다. 줄기세포의 골세포(osteocytes) 혹은 지방세포(adipocytes)로 분화하는 능력 역시 GV-Ex를 처리한 P-17 MSCs에서 개선되었다. 이상과 같은 결과를 통해, GV 추출물은 노화된 줄기세포의 기능을 개선함을 시사한다.

Keywords

References

  1. Arai, Y., Martin-Ruiz, C. M., Takayama, M., Abe, Y., Takebayashi, T., Koyasu, S., Suematsu, M., Hirose, N. and von Zglinicki, T. 2015. Inflammation, but not telomere length, predicts successful ageing at extreme old age: a longitudinal study of semi-supercentenarians. EBioMedicine 2, 1549-1558. https://doi.org/10.1016/j.ebiom.2015.07.029
  2. Biteau, B., Hochmuth, C. E. and Jasper, H. 2011. Maintaining tissue homeostasis: dynamic control of somatic stem cell activity. Cell Stem Cell 9, 402-411. https://doi.org/10.1016/j.stem.2011.10.004
  3. de Almeida, C. L., Falcao Hde, S., Lima, G. R., Montenegro Cde, A., Lira, N. S., de Athayde-Filho, P. F., Rodrigues, L. C., de Souza Mde, F., Barbosa-Filho, J. M. and Batista, L. M. 2011. Bioactivities from marine algae of the genus Gracilaria. Int. J. Mol. Sci. 12, 4550-4573. https://doi.org/10.3390/ijms12074550
  4. Fang, C., Gu, L., Smerin, D., Mao, S. and Xiong, X. 2017. The interrelation between reactive oxygen species and autophagy in neurological disorders. Oxid. Med. Cell. Longev. 2017, 8495160.
  5. Jeong, S. G. and Cho, G. W. 2015. Endogenous ROS levels are increased in replicative senescence in human bone marrow mesenchymal stromal cells. Biochem. Biophys. Res. Commun. 460, 971-976. https://doi.org/10.1016/j.bbrc.2015.03.136
  6. Jeong, S. G. and Cho, G. W. 2015. Trichostatin A modulates intracellular reactive oxygen species through SOD2 and FOXO1 in human bone marrow-mesenchymal stem cells. Cell Biochem. Funct. 33, 37-43. https://doi.org/10.1002/cbf.3084
  7. Jeong, S. G. and Cho, G. W. 2016. Accumulation of apoptosis-insensitive human bone marrow-mesenchymal stromal cells after long-term expansion. Cell Biochem. Funct. 34, 310-316. https://doi.org/10.1002/cbf.3191
  8. Johnson, F. and Giulivi, C. 2005. Superoxide dismutases and their impact upon human health. Mol. Aspects Med. 26, 340-352. https://doi.org/10.1016/j.mam.2005.07.006
  9. Kim, E. K., Lim, S., Park, J. M., Seo, J. K., Kim, J. H., Kim, K. T., Ryu, S. H. and Suh, P. G. 2012. Human mesenchymal stem cell differentiation to the osteogenic or adipogenic lineage is regulated by AMP-activated protein kinase. J. cell. Physi. 227, 1680-1687. https://doi.org/10.1002/jcp.22892
  10. Kim, M. H., Hong, H. N., Hong, J. P., Park, C. J., Kwon, S. W., Kim, S. H., Kang, G. and Kim, M. 2010. The effect of VEGF on the myogenic differentiation of adipose tissue derived stem cells within thermosensitive hydrogel matrices. Biomaterials 31, 1213-1218. https://doi.org/10.1016/j.biomaterials.2009.10.057
  11. Liu, L. and Rando, T. A. 2011. Manifestations and mechanisms of stem cell aging. J. Cell Biol. 193, 257-266. https://doi.org/10.1083/jcb.201010131
  12. Lu, T. and Finkel, T. 2008. Free radicals and senescence. Exp. Cell Res. 314, 1918-1922. https://doi.org/10.1016/j.yexcr.2008.01.011
  13. Luceri, C., Bigagli, E., Femia, A. P., Caderni, G., Giovannelli, L. and Lodovici, M. 2018. Aging related changes in circulating reactive oxygen species (ROS) and protein carbonyls are indicative of liver oxidative injury. Toxicol. Rep. 5, 141-145. https://doi.org/10.1016/j.toxrep.2017.12.017
  14. Marcus, A. J., Coyne, T. M., Rauch, J., Woodbury, D. and Black, I. B. 2008. Isolation, characterization, and differentiation of stem cells derived from the rat amniotic membrane. Differentiation 76, 130-144. https://doi.org/10.1111/j.1432-0436.2007.00194.x
  15. Mazarrasa, I., Olsen, Y. S., Mayol, E., Marba, N. and Duarte, C. M. 2014. Global unbalance in seaweed production, research effort and biotechnology markets. Biotechnol. Adv. 32, 1028-1036. https://doi.org/10.1016/j.biotechadv.2014.05.002
  16. Nguyen, A., Leblond, F., Mamarbachi, M., Geoffroy, S. and Thorin, E. 2016. Age-dependent demethylation of Sod2 promoter in the mouse femoral artery. Oxid. Med. Cell. Longev. 2016, 8627384.
  17. Okuda, K., Bardeguez, A., Gardner, J. P., Rodriguez, P., Ganesh, V., Kimura, M., Skurnick, J., Awad, G. and Aviv, A. 2002. Telomere length in the newborn. Pediatr. Res. 52, 377-381. https://doi.org/10.1203/00006450-200209000-00012
  18. Pellettieri, J. and Sanchez Alvarado, A. 2007. Cell turnover and adult tissue homeostasis: from humans to planarians. Annu. Rev. Genet. 41, 83-105. https://doi.org/10.1146/annurev.genet.41.110306.130244
  19. Piazza, N., Hayes, M., Martin, I., Duttaroy, A., Grotewiel, M. and Wessells, R. 2009. Multiple measures of functionality exhibit progressive decline in a parallel, stochastic fashion in Drosophila Sod2 null mutants. Biogerontology 10, 637-648. https://doi.org/10.1007/s10522-008-9210-2
  20. Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., Moorman, M. A., Simonetti, D. W., Craig, S. and Marshak, D. R. 1999. Multilineage potential of adult human mesenchymal stem cells. Science 284, 143-147. https://doi.org/10.1126/science.284.5411.143
  21. Rossi, D. J., Jamieson, C. H. and Weissman, I. L. 2008. Stems cells and the pathways to aging and cancer. Cell 132, 681-696. https://doi.org/10.1016/j.cell.2008.01.036
  22. Strasser, A., O'Connor, L. and Dixit, V. M. 2000. Apoptosis signaling. Annu. Rev. Biochem. 69, 217-245. https://doi.org/10.1146/annurev.biochem.69.1.217
  23. Vehvilainen, P., Koistinaho, J. and Gundars, G. 2014. Mechanisms of mutant SOD1 induced mitochondrial toxicity in amyotrophic lateral sclerosis. Fron. Cell. Neurosci. 8, 126.
  24. Watanabe, K., Shibuya, S., Ozawa, Y., Nojiri, H., Izuo, N., Yokote, K. and Shimizu, T. 2014. Superoxide dismutase 1 loss disturbs intracellular redox signaling, resulting in global age-related pathological changes. BioMed Res. Internat. 2014, 140165.
  25. Yang, J. I., Yeh, C. C., Lee, J. C., Yi, S. C., Huang, H. W., Tseng, C. N. and Chang, H. W. 2012. Aqueous extracts of the edible Gracilaria tenuistipitata are protective against H(2)O(2)-induced DNA damage, growth inhibition, and cell cycle arrest. Molecules 17, 7241-7254. https://doi.org/10.3390/molecules17067241