The brominated pyrrole-imidazole Ageladine A was used for live imaging of the jellyfish (jellies) Nausithoe werneri, the sea anemone Metridium senile and the flatworm Macrostomum lignano. The fluorescence properties of Ageladine A allow for estimation of pH values in tissue and organs in living animals. The results showed that Nausithoe werneri had the most acidic areas in the tentacles and close to the mouth (pH 4–6.5), Metridium senile harbours aggregates of high acidity in the tentacles (pH 5) and in Macrostomum lignano, the rhabdoids, the gonads and areas close to the mouth were the most acidic with values down to pH 5.
References
[1]
Melo, M.J. History of Natural Dyes in the Ancient Mediterranean World. In Handbook of Natural Colorants; John Wiley & Sons: Hoboken, NJ, USA, 2009; pp. 3–20.
[2]
Fujita, M.; Nakao, Y.; Matsunaga, S.; Seiki, M.; Itoh, Y.; Yamashita, J.; van Soest, R.W.; Fusetani, N. Ageladine A: An antiangiogenic matrixmetalloproteinase inhibitor from the marine sponge Agelas nakamurai. J. Am. Chem. Soc. 2003, 125, 15700–15701, doi:10.1021/ja038025w. 14677933
[3]
Assmann, M.; Lichte, E.; van Soest, R.W.; K？ck, M. New bromopyrrole alkaloids from the marine sponge Agelas wiedenmayeri. Org. Lett. 1999, 1, 455–457, doi:10.1021/ol990664h.
[4]
Shengule, S.R.; Karuso, P. Concise total synthesis of the marine natural product Ageladine A. Org. Lett. 2006, 31, 4083–4084.
[5]
Meketa, M.L.; Weinreb, S.M. Total synthesis of Ageladine A, an angiogenesis inhibitor from the marine sponge Agelas nakamurai. Org. Lett. 2006, 30, 1443–1446.
[6]
Ando, N.; Terashima, S. Synthesis of novel Ageladine A analogs showing more potent matrix metalloproteinase (MMP)-12 inhibitory activity than the natural product. Bioorg. Med. Chem. Lett. 2009, 19, 5461–5463, doi:10.1016/j.bmcl.2009.07.099. 19665375
[7]
Naoki, A.; Terashima, S. Synthesis and matrixmetalloproteinase-12 inhibitory activity of Ageladine A analogs. Chem. Pharm. Bull. 2011, 59, 579–596, doi:10.1248/cpb.59.579. 21532196
[8]
Ma, Y.; Nam, S.; Jove, R.; Yakushijin, K.; Horne, D.A. Synthesis and anticancer activities of Ageladine A and structural analogs. Bioorg. Med. Chem. Lett. 2010, 20, 83–86. 19948404
[9]
Shengule, S.R.; Loa-Kum-Cheung, W.L.; Parish, C.R.; Blairvacq, M.; Meijer, L.; Nakao, Y.; Karuso, P. A one-pot synthesis and biological activity of Ageladine A and analogues. J. Med. Chem. 2011, 54, 2492–2503, doi:10.1021/jm200039m. 21413800
[10]
Bickmeyer, U.; Grube, A.; Klings, K.W.; K？ck, M. Ageladine A, a pyrrole-imidazole alkaloid from marine sponges, is a pH sensitive membrane permeable dye. Biochem. Biophys. Res. Commun. 2008, 373, 419–422, doi:10.1016/j.bbrc.2008.06.056. 18588854
[11]
Bickmeyer, U.; Heine, M.; Podbielski, I.; Münd, D.; K？ck, M.; Karuso, P. Tracking of fast moving neuronal vesicles with Ageladine A. Biochem. Biophys. Res. Commun. 2010, 402, 489–494, doi:10.1016/j.bbrc.2010.10.055. 20955687
[12]
Parks, S.K.; Chiche, J.; Pouyssegur, J. pH control mechanisms of tumor survival and growth. J. Cell. Physiol. 2011, 226, 299–308, doi:10.1002/jcp.22400. 20857482
[13]
Webb, B.A.; Chimenti, M.; Jacobson, M.P.; Barber, D.L. Dysregulated pH: A perfect storm for cancer progression. Nat. Rev. Cancer 2011, 11, 671–677, doi:10.1038/nrc3110. 21833026
[14]
Madshus, I.H. Regulation of intracellular pH in eukaryotic cells. Biochem. J. 1988, 250, 1–8. 2965576
[15]
Bock, C.; Sartoris, F.J.; Wittig, W.M.; P？rtner, H.O. Temperature-dependent pH regulation in stenothermal antarctic and eurythermal temperate eelpout (Zoarcidae): An in-vivo NMR study. Polar Biol. 2001, 24, 869–874, doi:10.1007/s003000100298.
[16]
Melzner, F.; Bock, C.; P？rtner, H.O. Critical temperatures in the cephalopod Sepia officinalis investigated using in vivo 31P NMR spectroscopy. J. Exp. Biol. 2006, 209, 891–906, doi:10.1242/jeb.02054. 16481578
[17]
Sokolova, I.M.; Bock, C.; P？rtner, H.O. Resistance to freshwater exposure in White Sea Littorina spp. II: Acid-base regulation. J. Comp. Physiol. 2000, 170, 105–115.
[18]
P？rtner, H.O.; Bock, C.; Reipschl？ger, A. Modulation of the cost of pHi regulation during metabolic depression: A 31P-NMR study in invertebrate (Sipunculus nudus) isolated muscle. J. Exp. Biol. 2000, 203, 2417–2428. 10903156
[19]
Wheatly, M.G.; Henry, R.P. Extracellular and intracellular acid-base regulation in crustaceans. J. Exp. Zool. 1992, 263, 127–142, doi:10.1002/jez.1402630204.
[20]
Ladurner, P.; Sch？rer, L.; Salvenmoser, W.; Rieger, R.M. A new model organism among the lower Bilateria and the use of digital microscopy intaxonomy of meiobenthic Platyhelminthes: Macrostomum lignano, n. sp. (Rhabditophora, Macrostomorpha). J. Zool. Syst. Evol. Res. 2005, 43, 114–126, doi:10.1111/j.1439-0469.2005.00299.x.
[21]
Jarms, G. Neubeschreibung dreier Arten der Gattung Nausithoe (Coronata, Scyphozoa) sowie Wiederbeschreibung der Art Nausithoe marginata Kolliker, 1853. Mitt. Hamb. Zool. Mus. Inst. 1990, 87, 7–39.
[22]
Berking, S.; Herrmann, K. Formation and discharge of nematocysts is controlled by a proton gradient across the cyst membrane. Helgol. Mar. Res. 2006, 60, 180–188, doi:10.1007/s10152-005-0019-y.
[23]
Schuett, C.; Doepke, H.; Grathoff, A.; Gedde, M. Bacterial aggregates in the tentacles of the sea anemone Metridium senile. Helgol. Mar. Res. 2007, 61, 211–216, doi:10.1007/s10152-007-0069-4.
[24]
Rieger, R.M. 100 Years of Research on ‘Turbellaria’. Hydrobiologia 1998, 383, 1–27, doi:10.1023/A:1003423025252.
[25]
de Souza, S.A.; Leal-Zanchet, A.M. Histological and histochemicalcharacterization of the secretory cells of Choeradoplana iheringi Graff, 1899 (Platyhelminthes: Tricladida: Terricola). Braz. J. Biol. 2004, 64, 511–522. 15622848
[26]
Shum, W.W.C.; da Silva, N.; Brown, D.; Breton, S. Regulation of luminal acidification in the male reproductive tract via cell-cell crosstalk. Exp. Biol. 2009, 212, 1753–1761, doi:10.1242/jeb.027284.
[27]
Hamaguchi, M.S.; Watanabe, K.; Hamaguchi, Y. Regulation of intracellular pH in sea urchin eggs by medium containing both weak acid and base. Cell Struct. Funct. 1997, 22, 387–398, doi:10.1247/csf.22.387. 9368712
[28]
Bickmeyer, U.; Drechsler, C.; K？ck, M.; Assmann, M. Brominated pyrrole alkaloids from marine Agelas sponges reduce depolarization-induced cellular calcium elevation. Toxicon 2004, 44, 45–51, doi:10.1016/j.toxicon.2004.04.001. 15225561
[29]
Bickmeyer, U.; Grube, A.; Klings, K.W.; K？ck, M. Disturbance of voltage-induced cellular calcium entry by marine dimeric and tetrameric pyrrole-imidazole alkaloids. Toxicon 2007, 50, 490–497, doi:10.1016/j.toxicon.2007.04.015. 17570456
[30]
Pawlik, J.R.; Chanas, B.; Toonen, R.; Fenical, W. Defenses of Caribbean sponges against predatory reef fish. I. Chemical deterrency. Mar. Ecol. Prog. Ser. 1995, 127, 183–194, doi:10.3354/meps127183.
[31]
Shimomura, O.; Johnson, F.H.; Saiga, Y. Extraction, purification and properties of aequorin, a bioluminescent protein from the luminous hydromedusan, Aequorea. J. Cell. Comp. Physiol. 1962, 59, 223–239, doi:10.1002/jcp.1030590302. 13911999
[32]
Tsien, R.Y. The green fluorescent protein. Annu. Rev. Biochem. 1998, 67, 509–544, doi:10.1146/annurev.biochem.67.1.509. 9759496
