Korean Journal of Food Science and Technology (한국식품과학회지)

Korean Society of Food Science and Technology (한국식품과학회)
권호 표지
DOI QR코드

DOI QR Code

Cellular Flavonoid Transport Mechanisms in Animal and Plant Cells

플라보노이드 세포 수송 기전

  • Han, Yoo-Li (Department of Food Bioscience and Technology, College of Life Sciences and Biotechnology) ;
  • Lee, So-Young (Department of Food Bioscience and Technology, College of Life Sciences and Biotechnology) ;
  • Lee, Ji Hae (Department of Food Bioscience and Technology, College of Life Sciences and Biotechnology) ;
  • Lee, Sung-Joon (Department of Food Bioscience and Technology, College of Life Sciences and Biotechnology)
  • 한유리 (고려대학교 생명과학대학 식품공학과) ;
  • 이소영 (고려대학교 생명과학대학 식품공학과) ;
  • 이지혜 (고려대학교 생명과학대학 식품공학과) ;
  • 이성준 (고려대학교 생명과학대학 식품공학과)
  • Received : 2012.09.11
  • Accepted : 2012.11.10
  • Published : 2013.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

Flavonoids have various biological activities; however, their cellular uptake mechanism is beginning to be understood only recently. This review focuses on cellular flavonoids transport mechanisms in both plants and animals. In plants, flavonoids exist in various cellular compartments, providing a specialized transport system. Newly synthesized flavonoids can be transported from the endoplasmic reticulum to the vacuoles or extracellular space via cellular trafficking pathway. Among membrane transporters, ATP binding cassette, multidrug and toxic extrusion, bilitranslocase homologue transporters play roles in both the influx and efflux of cellular flavonoids across the cell membrane. In recent years, extensive researches have provided a better understanding on the cellular flavonoid transport in mammalian cells. Bilitranslocase transports flavonoids in various tissues, including the liver, intestine and kidneys. However, other transport mechanisms are largely unknown and thus, further investigation should provide detailed mechanisms, which can potentially lead to an improved bioavailability and cellular function of flavonoids in humans.

플라보노이드는 식물의 주요 2차 대사산물 중 하나로 자외선 차단, 식물의 수분을 위한 곤충 유인 등 외부환경에 적응하는데 이로운 역할을 한다. 특히 플라보노이드는 항산화 효과가 우수한 것으로 알려져 노화방지와 생활습관 질병예방에 유용한 건강기능식품소재로 각광받고 있다. 하지만 플라보노이드의 생체이용률은 매우 낮으며 이러한 플라보노이드 흡수과정에 관한 생물학적기전은 최근에 조금씩 밝혀지기 시작하고 있다. 플라보노이드의 수송기전에는 세포 내에서 일어나는 소포체 매개 수송과 세포막 및 소기관 표면 단백질에 의한 막 수송체 매개 수송이 있다. 소포체 매개 수송의 경우 cellular trafficking에 의한 일련의 소포체 유래 vesicle의 융합 반응을 거쳐 식물 세포의 경우 액포 내에 플라보노이드가 축적되거나 세포 외부로 배출된다. 표면 단백질에 의해 플라보노이드의 세포막 흡수가 일어나게 되는데 ATP를 사용한 능동수송, 막 전위를 이용한 2차 수송에 관여하는 다수의 수송체들이 관여하는 것으로 보인다. 다양한 종류의 플라보노이드가 존재하는 만큼 플라보노이드 수송체도 다양하며 어쩌면 모든 플라보노이드의 특이적 수송체를 규명하는 것은 불가능 할 지도 모른다. 하지만 식품에 다량 존재하는 주요 플라보노이드를 모델 화합물로 이용한 연구를 수행하면 이에 관련된 주요 수송체 단백질과 관련 메커니즘에 대해 깊이 이해할 수 있고 이를 통해 생체 이용률을 향상시키는 방법을 생각해 볼 수 있으며 특히 낮은 혈중 농도 조건에서도 조직 세포 내에 플라보노이드 축적을 통해 건강 기능성을 최적화하는 노력을 기울이는데 적절한 과학적 방법을 제시해 줄 수 있을 것으로 기대한다.

Keywords

References

  1. Harborne JB, Williams CA. Advances in flavonoid research since 1992. Phytochemistry 55: 481-504 (2000) https://doi.org/10.1016/S0031-9422(00)00235-1
  2. Zhao J, Dixon RA. The 'ins' and 'outs' of flavonoid transport. Trends Plant Sci. 15: 72-80 (2010)
  3. Rice-Evans CA, Miller NJ, Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radical Bio. Med. 20: 933-956 (1996) https://doi.org/10.1016/0891-5849(95)02227-9
  4. Teillet F, Boumendjel A, Boutonnat J, Ronot X. Flavonoids as RTK inhibitors and potential anticancer agents. Med. Res. Rev. 28: 715-745 (2008) https://doi.org/10.1002/med.20122
  5. Moutsatsou P. The spectrum of phytoestrogens in nature: our knowledge is expanding. Hormones (Athens) 6: 173-193 (2007)
  6. Hu JN, Huang Y, Xiong MR, Luo SF, Chen Y. The effects of natural flavonoids on lipoxygenase-mediated oxidation of compounds with a benzene ring structure - A new possible mechanism of flavonoid anti-chemical carcinogenesis and other toxicities. Int. J. Toxicol. 25: 295-301 (2006) https://doi.org/10.1080/10915810600746122
  7. Kinjo J, Tsuchihashi R, Morito K, Hirose T, Aomori T, Nagao T, Okabe H, Nohara T, Masamune Y. Interactions of phytoestrogens with estrogen receptors $\alpha$ and $\beta$ (III). Estrogenic activities of soy isoflavone aglycones and their metabolites isolated from human urine. Biol. Pharm. Bull. 27: 185-188 (2004) https://doi.org/10.1248/bpb.27.185
  8. Manach C, Scalbert A, Morand C, Remesy C, Jimenez L. Polyphenols: Food sources and bioavailability. Am. J. Clin. Nutr. 79: 727-747 (2004)
  9. Passamonti S, Terdoslavich M, Franca R, Vanzo A, Tramer F, Braidot E, Petrussa E, Vianello A. Bioavailability of flavonoids: A review of their membrane transport and the function of bilitranslocase in animal and plant organisms. Curr. Drug. Metab. 10: 369-394 (2009) https://doi.org/10.2174/138920009788498950
  10. Grotewold E. The challenges of moving chemicals within and out of cells: Insights into the transport of plant natural products. Planta 219: 906-909 (2004)
  11. Poustka F, Irani NG, Feller A, Lu Y, Pourcel L, Frame K, Grotewold E. A trafficking pathway for anthocyanins overlaps with the endoplasmic reticulum-to-vacuole protein-sorting route in arabidopsis and contributes to the formation of vacuolar inclusions. Plant Physiol. 145: 1323-1335 (2007) https://doi.org/10.1104/pp.107.105064
  12. Zhang HB, Wang L, Deroles S, Bennett R, Davies K. New insight into the structures and formation of anthocyanic vacuolar inclusions in flower petals. BMC Plant Biol. 6: 29 (2006) https://doi.org/10.1186/1471-2229-6-29
  13. Hsieh K, Huang AHC. Tapetosomes in Brassica tapetum accumulate endoplasmic reticulum-derived flavonoids and alkanes for delivery to the pollen surface. Plant Cell. 19: 582-596 (2007) https://doi.org/10.1105/tpc.106.049049
  14. Linton KJ, Higgins CF. The Escherichia coli ATP-binding cassette (ABC) proteins. Mol. Microbiol. 28: 5-13 (1998)
  15. Dean M, Rzhetsky A, Allikmets R. The human ATP-binding cassette (ABC) transporter superfamily. Genome Res. 11: 1156-1166 (2001) https://doi.org/10.1101/gr.GR-1649R
  16. Sanchez-Fernandez R, Davies TGE, Coleman JOD, Rea PA. The Arabidopsis thaliana ABC protein superfamily, a complete inventory. J. Biol. Chem. 276: 30231-30244 (2001) https://doi.org/10.1074/jbc.M103104200
  17. Rea PA. Plant ATP-Binding cassette transporters. Annu. Rev. Plant Biol. 58: 347-375 (2007) https://doi.org/10.1146/annurev.arplant.57.032905.105406
  18. Sugiyama A, Shitan N, Yazaki K. Involvement of a soybean ATP-binding cassette-type transporter in the secretion of genistein, a signal flavonoid in legume-Rhizobium symbiosis (1). Plant Physiol. 144: 2000-2008 (2007) https://doi.org/10.1104/pp.107.096727
  19. Goodman CD, Casati P, Walbot V. A multidrug resistance-associated protein involved in anthocyanin transport in Zea mays. Plant Cell. 16: 1812-1826 (2004) https://doi.org/10.1105/tpc.022574
  20. Buer CS, Muday GK, Djordjevic MA. Flavonoids are differentially taken up and transported long distances in arabidopsis. Plant Physiol. 145: 478-490 (2007) https://doi.org/10.1104/pp.107.101824
  21. Moriyama Y, Hiasa M, Matsumoto T, Omote H. Multidrug and toxic compound extrusion (MATE)-type proteins as anchor transporters for the excretion of metabolic waste products and xenobiotics. Xenobiotica 38: 1107-1118 (2008) https://doi.org/10.1080/00498250701883753
  22. Frangne N, Eggmann T, Koblischke C, Weissenbock G, Martinoia E, Klein M. Flavone glucoside uptake into barley mesophyll and arabidopsis cell culture vacuoles. Energization occurs by $H^{+}$-antiport and ATP-binding cassette-type mechanisms. Plant Physiol. 128: 726-733 (2002) https://doi.org/10.1104/pp.010590
  23. Gomez C, Terrier N, Torregrosa L, Vialet S, Fournier-Level A, Verries C, Souquet JM, Mazauric JP, Klein M, Cheynier V, Ageorges A. Grapevine MATE-type proteins act as vacuolar $H^{+}$- dependent acylated anthocyanin transporters. Plant Physiol. 150: 402-415 (2009) https://doi.org/10.1104/pp.109.135624
  24. Mathews H, Clendennen SK, Caldwell CG, Liu XL, Connors K, Matheis N, Schuster DK, Menasco DJ, Wagoner W, Lightner J, Wagner DR. Activation tagging in tomato identifies a transcriptional regulator of anthocyanin biosynthesis, modification, and transport. Plant Cell 15: 1689-1703 (2003) https://doi.org/10.1105/tpc.012963
  25. Passamonti S, Cocolo A, Braidot E, Petrussa E, Peresson C, Medic N, Macri F, Vianello A. Characterization of electrogenic bromosulfophthalein transport in carnation petal microsomes and its inhibition by antibodies against bilitranslocase. FEBS J. 272: 3282-3296 (2005) https://doi.org/10.1111/j.1742-4658.2005.04751.x
  26. Braidot E, Petrussa E, Bertolini A, Peresson C, Ermacora P, Loi N, Terdoslavich M, Passamonti S, Macri F, Vianello A. Evidence for a putative flavonoid translocator similar to mammalian bilitranslocase in grape berries (Vitis vinifera L.) during ripening. Planta 228: 203-213 (2008) https://doi.org/10.1007/s00425-008-0730-4
  27. Lunazzi G, Tiribelli C, Gazzin B, Sottocasa G. Further-studies on bilitranslocase, a plasma-membrane protein involved in hepatic organic anion uptake. Biochim. Biophys. Acta 685: 117-122 (1982) https://doi.org/10.1016/0005-2736(82)90087-6
  28. Karawajczyk A, Dran V, Medic N, Oboh G, Passamonti S, Novic M. Properties of flavonoids influencing the binding to bilitranslocase investigated by neural network modelling. Biochem. Pharmacol. 73: 308-320 (2007) https://doi.org/10.1016/j.bcp.2006.09.024
  29. Passamonti S, Vrhovsek U, Mattivi F. The interaction of anthocyanins with bilitranslocase. Biochem. Bioph. Res. Comm. 296: 631-636 (2002) https://doi.org/10.1016/S0006-291X(02)00927-0
  30. Battiston L, Macagno A, Passamonti S, Micali F, Sottocasa GL. Specific sequence-directed anti-bilitranslocase antibodies as a tool to detect potentially bilirubin-binding proteins in different tissues of the rat. FEBS Lett. 453: 351-355 (1999) https://doi.org/10.1016/S0014-5793(99)00736-X
  31. Elias MM, Lunazzi GC, Passamonti S, Gazzin B, Miccio M, Stanta G, Sottocasa GL, Tiribelli C. Bilitranslocase localization and function in basolateral plasma-membrane of renal proximal tubule in rat. Am. J. Physiol. 259: F559-F564 (1990)
  32. Vanzo A, Terdoslavich M, Brandoni A, Torres AM, Vrhovsek U, Passamonti S. Uptake of grape anthocyanins into the rat kidney and the involvement of bilitranslocase. Mol. Nutr. Food Res. 52: 1106-1116 (2008) https://doi.org/10.1002/mnfr.200700505
  33. Yen TH, Wright NA. The gastrointestinal tract stem cell niche. Stem Cell Rev. 2: 203-212 (2006) https://doi.org/10.1007/s12015-006-0048-1
  34. Murota K, Terao J. Quercetin appears in the lymph of unanesthetized rats as its phase II metabolites after administered into the stomach. FEBS Lett. 579: 5343-5346 (2005) https://doi.org/10.1016/j.febslet.2005.08.060

Cited by

  1. Comparison of Antioxidant and Antimicrobial Activities of Bracken (Pteridium aquilinum Kuhn) according to Cooking Methods vol.27, pp.3, 2014, https://doi.org/10.9799/ksfan.2014.27.3.348
  2. Comparison of Antioxidant and Antimicrobial Activities in Siraegi (Dried Radish Greens) according to Cooking Process vol.27, pp.4, 2014, https://doi.org/10.9799/ksfan.2014.27.4.609
  3. Antioxidant Component and Sensory Evaluation of Mixed Cereals vol.28, pp.2, 2015, https://doi.org/10.9799/ksfan.2015.28.2.196