Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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The role of noble bumblebee (Bombus terrestris) queen glycosaminoglycan in aged rat and gene expression profile based on DNA microarray

  • Ahn, Mi Young (Department of Agricultural Biology, National Institute of Agricultural Sciences, Rural Development Administration (RDA)) ;
  • Yoon, Hyung Joo (Department of Agricultural Biology, National Institute of Agricultural Sciences, Rural Development Administration (RDA)) ;
  • Hwang, Jae Sam (Department of Agricultural Biology, National Institute of Agricultural Sciences, Rural Development Administration (RDA)) ;
  • Jin, Jang Mi (Korean Basic Science Institute) ;
  • Park, Kun-Koo (Pharmacogenechips Inc)
  • Received : 2020.04.28
  • Accepted : 2020.09.23
  • Published : 2021.01.15
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Abstract

Glycosaminoglycans (GAGs) have been used to diminish the deleterious effects associated with aging by preventing the destruction of cartilage, bone, discs, and skin. The objective of this study was to evaluate the anti-aging effect of a newly prepared GAG derived from bumblebee (Bombus terrestris) queen (BTQG, 10 mg/kg). Gryllus bimaculatus (Gb, cricket) GAG (GbG, 10 mg/kg) or glucosamine sulfate (GS) was used as a positive control. N-glycans derived from BTQG contained hexose polymers including Hex4HexNAc3Pen1, Hex9, and Hex5HexNAc3dHex2 as the primary components. The GAGs were intraperitoneally administered to 14-month-old aged rats for 1 month. BTQG reduced the serum levels of free fatty acid, alkaline phosphatase (ALP), glutamate pyruvate transaminase (GPT), creatinine, and blood urea nitrogen (BUN), showing hepato-and renal-protective effects with anti-lipidemic activities comparable to GS. The changes of gene expression profile of liver tissue by cDNA microarray showed the simultaneous upregulation of 36 genes in the BTQG-treated rat group compared to the control group, including secretogranin II (Scg2), Activator (AP)-1-regulated protein-related reactive oxygen species (ROS) DNA damage repair, metallothionein 1a, and alpha-2 macroglobulin. The BTQG-treated group also showed 417 downregulated genes, including vimentin, moesin, and mitochondrial carbonic anhydrase. Insect glycosaminoglycan from the bumblebee (B. terrestris) queen may help decelerate the aging stage by ameliorating the aging effects on circulation, and liver and kidney function.

Keywords

Acknowledgement

The authors acknowledge National Institute of Agricultural Sciences for financial (RDA, PJ011853) and technical supports. Technical support for analysis of N-glycan sequence data was obtained from Division of Mass Spectrometry Research of Korean Basic Science Institute.

References

  1. Eisenberg T, Abdellatif M, Schroeder S, Primessnig U, Stekovic S, Pendl T, Harger A, Schipke J, Zimmermann A, Schmidt A, Tong M, Ruckenstuhl C, Dammbrueck C, Gross AS, Herbst V, Magnes C, Trausinger G, Narath S, Meinitzer A, Hu Z, Kirsch A, Eller K, Carmona-Gutierrez D, Buttner S, Pietrocola F, Knittelfelder O, Schrepfer E, Rockenfeller P, Simonini C, Rahn A, Horsch M, Moreth K, Beckers J, Fuchs H, Gailus-Durner V, Neff F, Janik D, Rathkolb B, Rozman J, de Angelis MH, Moustafa T, Haemmerle G, Mayr M, Willeit P, von Frieling-Salewsky M, Pieske B, Scorrano L, Pieber T, Pechlaner R, Willeit J, Sigrist SJ, Linke WA, Muhlfeld C, Sadoshima J, Dengjel J, Kiechl S, Kroemer G, Sedej S, Madeo F (2016) Cardioprotection and lifespan extension by the natural polyamine spermidine. Nat Med 22:1428-1438. https://doi.org/10.1038/nm.4222
  2. Shute JK, Puxeddu E, Calzetta L (2018) Therapeutic use of heparin and derivatives beyond anticoagulation in patients with bronchial asthma or COPD. Curr Opin Pharm 40:39-45. https://doi.org/10.1016/j.coph.2018.01.006
  3. Ahn MY, Kim SJ, Kim NJ, Hwang JS, Yun EY (2015) Immune modulation of glycosaminoglycan derived from P. lewisi in TNF-α stimulated cells. Arch Pharm Res 38:1983-1991. https://doi.org/10.1007/s12272-015-0616-5
  4. Ahn MY, Han JW, Yoon HJ, Hwang JS (2012) Anti-inflammatory effect of bumblebee alcohol extracts in CFA-induced rat edema. Toxicol Res 28:249-253. https://doi.org/10.5487/TR.2012.28.4.249
  5. Ahn MY, Kim BJ, Kim HJ, Jin JM, Yoon HJ, Hwang JS, Park KK (2019) Anti-cancer effect of dung beetle glycosaminoglycans on melanoma. BMC Cancer 19:9. https://doi.org/10.1186/s12885-018-5202-z
  6. Lee DF, Oh JH, Chung J (2016) Glycosaminoglycan and proteoglycan in skin aging. J Dermatol Sci 83:174-181. https://doi.org/10.1016/j.jdermsci.2016.05.016
  7. Wong TY, Chang C, Yu C, Huang LLH (2017) Hyaluronan keeps mesenchymal stem cells quiescent and maintains the differentiation potential over time. Aging Cell 16:451-460. https://doi.org/10.1111/acel.12567
  8. Majtan J, Bilikova K, Markovic O, Grof J, Kogan G, Smiuth J (2007) Isolation and characterization of chitin from bumblebee (Bombus terrestris). Int J Biol Macromol 40:237-241. https://doi.org/10.1016/j.ijbiomac.2006.07.010
  9. Weindruch R, Kayo T, Lee CK, Prolla TA (2001) Microarray profiling of gene expression in aging and its alteration by caloric restriction in mice. J Nutr 131:918S-923S. https://doi.org/10.1093/jn/131.3.918S
  10. Kim YS, Jo YY, Chang IM, Toida T, Park Y, Linhardt RJ (1996) A new glycosaminoglycan from the giant African snail Achatina fulica. J Biol Chem 271:11750-11755. https://doi.org/10.1074/jbc.271.20.11750
  11. Magnelli PE, Bielik AM, Guthrie EP (2011) Identification and characterization of protein glycosyation using specific endo- and exoglycosidases. J Vis Exp 58:e3749. https://doi.org/10.3791/3749
  12. Ahn MY, Hahn BS, Ryu KS, Kim JW, Kim YS (2003) Purification and characterization of a serine protease with fibrinolytic activity from dung beetles, Catharsius molossus. Thromb Res 112:339-347. https://doi.org/10.1016/j.thromres.2004.01.005
  13. Ahn MY, Kim BJ, Kim HJ, Hwang JS, Jung YS, Park KK (2017) Anti-aging effect and gene expression profiling of dung beetle glycosaminoglycan in aged rats. Biomater Res 21:5. https://doi.org/10.1186/s40824-017-0091-9
  14. Ueno T, Fukuda N, Nagase H, Tsunemi A, Tahira K, Matsumoto T, Hiraoka-Yamamoto J, Ikeda K, Mitsumata M, Sato Y, Soma M, Matsumoto K, Yamori Y (2009) Atherogenic dyslipidemia and altered hepatic gene expression in SHRSP.Z-Leprfa/IzmDmer rats. Int J Mol Med 23:313-320. https://doi.org/10.3892/ijmm_00000133
  15. Ahn MY, Joo HJ, Kim JS, Yeon Y, Ryu HY, Choi BG, Song KS, Kim SH, Park MK, Jo YY (2020) Toxicity assessment of Gryllus bimaculatus (a type of cricket) glycosaminoglycan. Toxicol Res. https://doi.org/10.1007/s43188-020-00037-2
  16. Ahn MY, Kim BJ, Kim HJ, Yoon HJ, Jee SD, Hwang JS, Park KK (2017) Anti-obesity effect of Bombus ignitus queen glycosaminoglycans in rats on a high-fat. Int J Mol Sci 18:681. https://doi.org/10.3390/ijms18030681
  17. Ahn MY, Hwang JS, Kim MJ, Park KK (2016) Antilipidemic effects and gene expression profiling of the glycosaminoglycans from cricket in rats on a high fat diet. Arch Pharm Res 39(926):936. https://doi.org/10.1007/s12272-016-0749-1
  18. Beattie MC, Chen H, Fan J, Papadopoulos V, Miller P, Zirkin BR (2013) Aging and luteinizing hormone effects on reactive oxygen species production and DNA damage in rat Leydig cells. Biol Reprod 88:100. https://doi.org/10.1095/biolreprod.112.107052
  19. Moehle EA, Shen K, Dillin A (2019) Mitochondrial proteostasis in the context of cellular and organismal health and aging. J Biol Chem 294:5396-5407. https://doi.org/10.1074/jbc.TM117.000893
  20. Cardoso AL, Fernandes A, Aquilar-Pimentel JA, de Angelis MH, Guedes JR, Brito MA, Ortolano S, Pani G, Athanasopoulou S, Gonos ES, Schosserer M, Grillari J, Peterson P, Tuna BG, Dogan S, Meyer A (2018) Towards frailty biomarkers: candidates from genes and pathways regulated in aging and age-related diseases. Ageing Res Rev 47:214-277. https://doi.org/10.1016/j.arr.2018.07.004
  21. Skulachev MV, Skulachev VP (2014) New data on programmed aging-slow phenoptosis. Biochemistry (Moscow) 79:977-993. https://doi.org/10.1134/S0006297914100010
  22. Donertas HM, Valenzuela MF, Partridge L (2018) Gene expression-based drug repurposing to target aging. Aging Cell 2018:e12819. https://doi.org/10.1111/acel.12819
  23. Bakun M, Senatorski G, Rubel T, Lukasik A, Zielenkiewicz P, Dadlez M, Paczek L (2014) Urine proteomes of healthy aging humans reveal extracellular matrix (ECM) alterations and immune system dysfunction. Age (Dordr) 36:299-311. https://doi.org/10.1007/s11357-013-9562-7
  24. Swindell WR (2011) Metallothionein and the biology of aging. Ageing Res Rev 10:132-145. https://doi.org/10.1016/j.arr.2010.09.007
  25. Cong W, Niu C, Lv L, Ni M, Ruan D, Chi L, Wang Y, Yu Q, Zhan K, Xuan Y, Wang Y, Tan Y, Wei T, Cai L, Jin L (2016) Metallothionein prevents age-associated cardiomyopathy via inhibiting NF-κB pathway activation and associated nitrative damage to 2-OGD. Antioxid Redox Signal 25:936-952. https://doi.org/10.1089/ars.2016.6648
  26. Thieme R, Kurz S, Kolb M, Debebe T, Holtze S, Morhart M, Huse K, Szafranski K, Platzer M, Hildebrandt TB, Birkenmeier G (2015) Analysis of alpha-2 macroglobulin from the long-lived and cancer resistant naked mole-rat and human plasma. PLoS ONE 10:e0130470. https://doi.org/10.1371/journal.pone.0130470
  27. Zaki SM, Mohamed EA, Abde I, Fattah S, Abdullah H, Kaszubowska L (2018) Age-associated functional morphology of thyroid and its impact on the expression of vimentin, cytokeratin and VEGF. The role of nigella in refinement. Folia Histochem Cytobiol 56:159-171. https://doi.org/10.5603/FHC.a2018.0015
  28. Lee JH, Hong IA, Oh SH, Kwon YS, Cho SH, Lee KH (2009) The effect of moesin overexpression on ageing of human dermal microvascular endothelial cells. Exp Dermatol 18:997-999. https://doi.org/10.1111/j.1600-0625.2009.00898.x
  29. Kong SZ, Li JC, Li SD, Liao MN, Li CP, Zheng PJ, Guo MH, Tan WX, Zheng ZH, Hu Z (2018) Anti-aging effect of chitosan oligosaccharide on d-galactose-induced subcute aging in mice. Mar drugs 16:181. https://doi.org/10.3390/md16060181
  30. Carbiscol E, Levine RL (1995) Carbonic anhydrase III. Oxidative modification in vivo and loss of phosphatase activity during aging. J Biol Chem 270:14742-14747. https://doi.org/10.1074/jbc.270.24.14742
  31. Sheikh MH, Solito E (2018) Annexin A1: uncovering the many talents of an old protein. Int J Mol Sci 19:1045. https://doi.org/10.3390/ijms19041045

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