Abstract
Quercetin (3,5,7,3',4'-pentahydroxyflavone) is one of the most abundant natural flavonoids. It is present in various common vegetables and fruits. In this report, we examined the effect of quercetin on melanogenesis using a three-dimensional reconstituted human epidermal culture model, MelanoDerm, which is a new commercially-available cultured human epidermis containing functional melanocytes. Treatment with 10 uM quercetin induced an increase of tyrosinase activity in cultured epidermis after 3–5 days in time-dependent manner. In the quercetin-treated epidermis, furthermore, melanin content and tyrosinase expression were markedly increased, as shown by immunohistochemistry after a 7-day culture period. Ultrastructural studies clearly indicated an accumulation of mature melanosomes (stages III and IV) inside the basal layer of the cultured epidermis after the quercetin treatment. In addition, the dendrites of melanocytes extended further towards the adjacent keratinocytes after quercetin treatment. These results suggest that quercetin has an effect on maturation of melanosomes and that quercetin has the potential to induced melanogenesis in human epidermis.
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Acott TS, Carr DW (1984) Inhibition of bovine spermatozoa by caudal epididymal fluid: II. Interaction of pH and a quiescence factor. Biol Reprod 30: 926–935.
Asari M, Sasaki K, Miura K, Ichihara N, Nishita T (1996) Immuno-histolocalization of the carbonic anhydrase isoenzymes (CA-I, CA-II, and CA-III) in the reproductive tract of male horses. Am J Vet Res 57: 439–443.
Au CL, Wong PY (1980) Luminal acidification by the perfused rat cauda epididymidis. J Physiol (Lond) 309: 419–427.
Babcock DF, Rufo Jr GA, Lardy HA (1983) Potassium-dependent increases in cytosolic pH stimulate metabolism and motility of mammalian sperm. Proc Natl Acad Sci USA 80: 1327–1331
Bagnis C, Marsolais M, Biemesderfer D, Laprade R, Breton S (2001) Na /H-exchange activity and immunolocalization of NHE3 in rat epididymis. Am J Physiol Renal Physiol 280: F426–F436.
Brown D, Montesano R (1980) Membrane specialization in the rat epididymis I. Rod-shaped intramembrane particles in the apical (mitochondria-rich) cell. J Cell Sci 45: 187–198.
Caflisch CR, DuBose Jr TD (1990) Direct evaluation of acidification by rat testis and epididymis: Role of carbonic anhydrase. Am J Physiol 258: E143–E150.
Carr DW, Usselman MC, Acott TS (1985) Effects of pH, lactate, and viscoelastic drag on sperm motility: Aspecies comparison. Biol Reprod 33: 588–595.
Chegwidden WR, Carter ND (2000) Introduction to the carbonic anhydrases. In: Chegwidden WR, Carter ND, Edwards YH, eds. The Carbonic Anhydrases.New Horizons. Basel: Birkh¨auser Verlag, pp. 13–28.
Cohen JP, Hoffer AP, Rosen S (1976) Carbonic anhydrase localization in the epidimymis and testis of the rat: Histochemical and biochemical analysis. Biol Reprod 14: 339–346.
Cooper TG (1986) The Epididymis, Sperm Maturation and Fertilization. Berlin: Springer-Verlag.
Demarco IA, Espinosa F, Edwards J, Sosnik J, De La Vega-Beltran JL, Hockensmith JW, Kopf GS, Darszon A, Visconti PE (2003) Involve-ment of a Na /HCOØÕ'`± 3 cotransporter in mouse sperm capacitation. J Biol Chem 278: 7001–7009.
Ekstedt E (1989) Carbonic anhydrase activity in male reproductive organs. Licentiate thesis. ISBN 91–576–3978–7, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Ekstedt E, Ridderstråle Y (1992) Histochemical localization of carbonic anhydrase in the testis and epididymis of the rabbit. Acta Anat (Basel) 143: 258–264.
Ekstedt E, Ridderstråle Y, Pl¨oen L, Rodriguez-Martinez H (1991) Histochemical localization of carbonic anhydrase in the testis and epididymis of the boar. Acta Anat (Basel) 141: 257–261.
Gatti JL, Chevrier C, Paquignon M, Dacheux JL (1993) External ionic conditions, internal pH and motility of ram and boar spermatozoa. J Reprod Fertil 98: 439–449.
Goyal HO, Ferguson JG, Hrudka F (1980) Histochemical activity of car-bonic anhydrase in testicular and excurrent ducts of immature, mature intact and androgen-deprived bulls. Biol Reprod 22: 991–997.
Hermo L, Adamali HI, Andonian S (2000) Immunolocalization of CA II and H V-ATPase in epithelial cells of the mouse and rat epididymis. J Androl 21: 376–391.
Holm L, Wishart GJ (1998) The effect of pH on the motility of spermatozoa from chicken, turkey and quail. Anim Reprod Sci 54: 45–54.
H¨ark¨onen PL, V¨a¨an¨anen HK (1988) Androgen regulation of carbonic anhydrase II, a major soluble protein in rat lateral prostate tissue. Biol Reprod 38: 377–384.
Ichihara N, Sasaki K, Iseri S, Kimura H, Miura K, Nishita T, Asari M (1997) Immunohistolocalization of carbonic anhydrase isozymes (CA-I, CA-II and CA-III) in bovine male reproductive tracts. Okajimas Folia Anat Jpn 74: 193–198.
Jensen LJ, Schmitt BM, Berger UV, Nsumu NN, Boron WF, Hediger MA, Brown D, Breton S (1999a) Localization of sodium bicarbonate cotransporter (NBC) protein and messenger ribonucleic acid in rat epididymis. Biol Reprod 60: 573–579.
Jensen LJ, Stuart-Tilley AK, Peters LL, Lux SE, Alper SL, Breton S (1999b) Immunolocalization of AE2 anion exchanger in rat and mouse epididymis. Biol Reprod 61: 973–980.
Karhumaa P, Kaunisto K, Parkkila S, Waheed A, Pastorekova S, Pastorek J, Sly WS, Rajaniemi H (2001) Expression of the transmem-brane carbonic anhydrases, CA IX and CA XII, in the human male excurrent ducts. Mol Hum Reprod 7: 611–616.
Karnovsky MJ (1965) A formaldehyde–glutaraldehyde fixative of high osmolality for use in electron microscopy. J Cell Biol 27: 137.
Kaunisto K, Fleming RE, Kneer J, Sly WS, Rajaniemi H(1999) Regional expression and androgen regulation of carbonic anhydrase IV and II in the adult rat epididymis. Biol Reprod 61: 1521–1526.
Kaunisto K, Parkkila S, Parkkila AK, Waheed A, Sly WS, Rajaniemi H (1995) Expression of carbonic anhydrase isoenzymes IV and II in rat epididymal duct. Biol Reprod 52: 1350–1357.
Lee MA, Storey BT (1986) Bicarbonate is essential for fertilization of mouse eggs: Mouse sperm require it to undergo the acrosome reaction. Biol Reprod 34: 349–356.
Levine N, Kelly H (1978) Measurement of pH in the rat epididymis in vivo. J Reprod Fertil 52: 333–335.
Levine N, Marsh DJ (1971) Micropuncture studies of the electrochemical aspects of fluid and electrolyte transport in individual seminiferous tubules, the epididymis and the vas deferens in rats. J Physiol (Lond) 213: 557–570.
Lewis SE, Erickson RP, Barnett LB, Venta PJ, Tashian RE (1988) N-ethyl-N-nitrosourea-induced null mutation at the mouse Car-2 locus: An animal model for human carbonic anhydrase II deficiency syndrome. Proc Natl Acad Sci USA 85: 1962–1966.
Okamura N, Tajima Y, Soejima A, Masuda H, Sugita Y (1985) Sodium bicarbonate in seminal plasma stimulates the motility of mammalian spermatozoa through direct activation of adenylate cyclase. J Biol Chem 260: 9699–9705.
Parkkila S, Kaunisto K, Kellokumpu S, Rajaniemi H (1991) A high acti-vity carbonic anhydrase isoenzyme (CA II) is present in mammalian spermatozoa. Histochemistry 95: 477–482.
Parkkila S, Parkkila AK, Kaunisto K, Waheed A, Sly WS, Rajaniemi H (1993a) Location of a membrane-bound carbonic anhy-drase isoenzyme (CA IV) in the human male reproductive tract. J Histochem Cytochem 41: 751–757.
Parkkila S, Rajaniemi H, Kellokumpu S (1993b) Polarized expression of a band 3-related protein in mammalian sperm cells. Biol Reprod 49: 326–331.
Ridderstråle Y (1976) Intracellular localization of carbonic anhydrase in the frog nephron. Acta Physiol Scand 98: 465–469.
Ridderstråle Y (1991) Localization of the carbonic anhydrases by chemical reactions. In: Dodgson SJ, Tashian RE, Gros G, Carter ND,eds. The Carbonic Anhydrases.Cellular Physiology and Molecular Genetics. New York: Plenum Press, pp. 133–144.
Robaire B, Hermo L (1988) Efferent ducts, epididymis, and vas deferens: Structure, functions, and their regulation. In: Knobil E, Neil JD,eds. The Physiology of Reproduction, 1. New York: Raven Press, pp. 999–1080.
Rodriguez-Martinez H, Ekstedt E, Einarsson S (1990) Acidification of epididymal fluid in the boar. Int J Androl 13: 238–243.
Soler C, Yeung CH, Cooper TG (1994) Development of sperm motility patterns in the murine epididymis. Int J Androl 17: 271–278.
Sterling D, Alvarez BV, Casey JR (2002) The extracellular compo-nent of a transport metabolon. Extracellular loop 4 of the human AE1 Cl-/HCO3-exchanger binds carbonic anhydrase IV. J Biol Chem 277: 25239–25246.
Tajima Y, Okamura N, Sugita Y (1987) The activating effects of bicarbonate on sperm motility and respiration at ejaculation. Biochim Biophys Acta 924: 519–529.
Waheed A, Zhu XL, Sly WS(1992) Membrane-associated carbonic anhy-drase from rat lung. Purification, characterization, tissue distribution, and comparison with carbonic anhydrase IVs of other mammals. J Biol Chem 267: 3308–3311.
Wistrand PJ, Wåhlstrand T (1977) Rat renal and erythrocyte carbonic anhydrases. Purification and properties. Biochim Biophys Acta 481: 712–721.
Yeung CH, Schroter S, Wagenfeld A, Kirchhoff C, Kliesch S, Poser D, Weinbauer GF, Nieschlag E, Cooper TG (1997) Interaction of the human epididymal protein CD52 (HE5) with epididymal spermatozoa from men and cynomolgus monkeys. Mol Reprod Dev 48: 267–275.
Zeng Y, Oberdorf JA, Florman HM (1996) pH regulation in mouse sperm: Identification of Na-, ClØÕ'`±-, and HCOØÕ'`± 3-dependent and arylaminobenzoate-dependent regulatory mechanisms and characteri-zation of their roles in sperm capacitation. Dev Biol 173: 510–520.
Zhang H, Martin-Deleon PA (2003) Mouse epididymal Spam1 (PH-20) is released in the luminal fluid with its lipid anchor. J Androl 24: 51–58.
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Takeyama, R., Takekoshi, S., Nagata, H. et al. Quercetin-Induced Melanogenesis in a Reconstituted Three-Dimensional Human Epidermal Model. Histochem J 35, 157–165 (2004). https://doi.org/10.1023/B:HIJO.0000023388.51625.6c
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DOI: https://doi.org/10.1023/B:HIJO.0000023388.51625.6c