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Chemical Compound Review

Indo-1     2-[4- (bis(carboxymethyl)amino)-3- [2-[2...

Synonyms: Indo 1, SureCN4079001, CHEBI:52084, AC1L2XYQ, LS-187497, ...
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Disease relevance of Indo-1

  • The whole-cell patch-clamp technique was used in combination with Indo-1-based microfluorometry to record Ca2+ current and [Ca2+]i simultaneously from single rat dorsal root ganglion (DRG) neurons grown in culture [1].
  • Thomas' Hospital solution and Stanford solution and subsequently reperfused for 1 h at 35 degrees C. In other groups of hearts, basal oxygen consumption and rest intracellular calcium (Indo 1 technique) were evaluated during ethanol-, hexanol- and potassium-induced cardiac arrest [2].
  • 3. Indo-1 was used to measure changes in intracellular calcium, [Ca2+]i. Anoxia reversibly increased [Ca2+]i from approximately 50-100 to approximately 200-450 nM in all cells tested [3].
  • 5. Scanning a single horizontal line across the cytoplasm with an ultraviolet argon ion laser (351 nm) and recording Indo-1 fluorescence with a confocal microscope demonstrated an inward spread of a rise in [Ca2+]i following a tetanus [4].
  • Although influenza virus itself did not generate O2-, it caused a transient increase in intracellular calcium ([Ca2+]i), when measured with Indo-1-loaded cells [5].

High impact information on Indo-1

  • Changes in Cai were measured in Indo-1-loaded neonatal human foreskin keratinocytes after stimulation with extracellular ATP [6].
  • To study the mediation of Ca2+ influx by second messengers in myeloid cells, we have combined the whole-cell patch clamp technique with microfluorimetric measurements of [Ca2+]i. Me2SO-differentiated HL-60 cells were loaded with the fluorescent Ca2+ indicator Indo-1, allowed to adhere to glass slides, and patch-clamped [7].
  • The average cytosolic [Ca2+] in various leukocyte populations was measured in Fura 2-loaded cell suspensions while the cytosolic [Ca2+] in individual, Indo 1-loaded leukocytes was assayed by flow cytometric methods [8].
  • The Ca2+ influx was examined directly by loading oligodendroglia with the fluorescent dye Indo-1 in defined medium, and measuring changes in Ca2+ in individual cells with a laser cytometer [9].
  • Confocal microscopy of astrocytes loaded with Indo-1 demonstrated that intercellular calcium wave transmission in IL-1beta-treated cultures was potentiated compared with controls [10].

Chemical compound and disease context of Indo-1

  • ROS generation was correlated with changing mitochondrial potential (rhodamine 123), [Ca2+]c (fluo-4, fura-2, or Indo-1), or ATP consumption, indicated by increased [Mg2+]c. We found that three distinct mechanisms contribute to neuronal injury by generating ROS and oxidative stress, each operating at a different stage of ischemia and reperfusion [11].

Biological context of Indo-1

  • Indo 1-loaded aggregates exhibit fluorescence transients during each transmembrane action potential [12].
  • To investigate whether free calcium levels are affected during apoptosis, we loaded egg chambers with the calcium indicator Indo-1 [13].
  • Tsien, Indo-1, has allowed us to resolve the temporal relationship between the rapid and transient cytoplasmic Ca2+ rise and the membrane potential change and to do so on very small samples by using a fluorescence-activated cell sorter [14].
  • Removal of IL-3 from cultures of 32D cells or control-transfected 32D-NEO cells for 1-2 days led to cell cycle arrest and oligonucleosomal DNA fragmentation and was associated with lower cytosolic free Ca2+ concentrations ([Ca2+]i), as measured by Indo-1 fluorescence of viable cells in Ca(2+)-containing media [15].
  • By using the calcium-sensitive dye Indo-1 and flow cytometry, we assessed CTL-target cell adhesion and CTL activation [16].

Anatomical context of Indo-1

  • Indo 1-loaded hearts were illuminated at 360 nm, and fluorescence was recorded simultaneously at 400 and 550 nm from the epicardial surface of the left ventricle [17].
  • METHODS AND RESULTS: Tissue resistance, intracellular Ca2+ concentration (Indo-1 fluorescence ratio), and mechanical activity were simultaneously determined in arterially perfused right ventricular papillary muscles from 11 normal and 15 failing rabbits [18].
  • The experiments were performed in isolated myocytes using the fluorescent indicators Indo-1 (to measure [Ca2+]i) and SBFI (to measure [Na+]i) [19].
  • Exposing Indo-1-labeled K562 cells to NmU induced an intracellular Ca(++) flux consistent with engagement of the NMU1R [20].
  • Depolarization with 40-60 mM K+ was used to analyze the activity of Ca2+ VOCs in Indo-1-loaded astrocytes in acute slices from the visual cortex and the CA1 hippocampal region of developing rats [21].

Associations of Indo-1 with other chemical compounds


Gene context of Indo-1

  • Simultaneous whole-cell recordings and ratiometric Indo-1 Ca2+ measurements indicated that agonist (CCh)-induced activation of TRPL channels was not always associated with a rise in Ca2+ [27].
  • Flow cytometric analysis by using Indo-1 showed that coaggregation of CD4, CD8, and CD2 with CD3/TCR clearly enhances a minimal signal delivered via CD3/TCR on immature thymocytes [28].
  • Indo-1 experiments revealed that TRH-increased [Ca2+]i was reversibly inhibited by Cd2+ [29].
  • With the major signal transduction pathway of endothelin-1 (ET1) acting via phospholipase C (PLC) and Ca2+, we used ET1 to analyse the nature of Ca2+ channels on cultured trophoblastic cells by means of cytofluorimetric analysis using the ratiometric Ca2+ indicator Indo-1 [30].
  • In addition, using fluorescent probes (Indo-1 and Boc-leu-met-MAC), we demonstrated that RGD120 added to prefusing myoblast cultures accelerates myoblast fusion into myotubes, induced an increase of cytosolic free calcium concentration, and concomitantly an increase of intracellular calpain protease activity [31].

Analytical, diagnostic and therapeutic context of Indo-1

  • In measurements of cytosolic free calcium concentration ([Ca2+]i) by flow cytometry in Indo-1-loaded platelets, ADP's dose-response for actin polymerization was similar to that for calcium mobilization [32].
  • We have taken advantage of laser photometry, the Ca2(+)-sensitive dye Indo-1 that allows ratio imaging, and confocal microscopy to eliminate the influences of unequal cell geometry and dye distribution [33].
  • With the calcium-sensitive dye, Indo-1, and immunofluorescence, we demonstrated that, despite the relative phenotypic immaturity of cells which express low levels of CD3/Ti alpha/beta, these antigen receptors are able to mediate transmembrane signaling when stimulated with CD3 monoclonal antibodies [34].
  • Quantitation of cytosolic [Ca2+] in whole perfused rat hearts using Indo-1 fluorometry [35].
  • 1. Single atrial myocytes obtained by enzyme perfusion from hearts of adult guinea-pigs were investigated using whole-cell voltage clamp and Indo-1 micro-fluorometry [36].


  1. Modulation of calcium efflux from cultured rat dorsal root ganglion neurons. Werth, J.L., Usachev, Y.M., Thayer, S.A. J. Neurosci. (1996) [Pubmed]
  2. Eighteen-hour preservation of rat hearts with hexanol and pyruvate cardioplegia. Kojima, S., Wu, S.T., Wikman-Coffelt, J., Parmley, W.W. J. Am. Coll. Cardiol. (1993) [Pubmed]
  3. Responses of type I cells dissociated from the rabbit carotid body to hypoxia. Biscoe, T.J., Duchen, M.R. J. Physiol. (Lond.) (1990) [Pubmed]
  4. Intracellular calcium dynamics in response to action potentials in bullfrog sympathetic ganglion cells. Nohmi, M., Hua, S.Y., Kuba, K. J. Physiol. (Lond.) (1992) [Pubmed]
  5. In vitro incubation with influenza virus primes human polymorphonuclear leukocyte generation of superoxide. Busse, W.W., Vrtis, R.F., Steiner, R., Dick, E.C. Am. J. Respir. Cell Mol. Biol. (1991) [Pubmed]
  6. Adenosine triphosphate stimulates phosphoinositide metabolism, mobilizes intracellular calcium, and inhibits terminal differentiation of human epidermal keratinocytes. Pillai, S., Bikle, D.D. J. Clin. Invest. (1992) [Pubmed]
  7. Regulation of Ca2+ influx in myeloid cells. Role of plasma membrane potential, inositol phosphates, cytosolic free [Ca2+], and filling state of intracellular Ca2+ stores. Demaurex, N., Schlegel, W., Varnai, P., Mayr, G., Lew, D.P., Krause, K.H. J. Clin. Invest. (1992) [Pubmed]
  8. Extracellular adenosine triphosphate activates calcium mobilization in human phagocytic leukocytes and neutrophil/monocyte progenitor cells. Cowen, D.S., Lazarus, H.M., Shurin, S.B., Stoll, S.E., Dubyak, G.R. J. Clin. Invest. (1989) [Pubmed]
  9. Glycolipids and transmembrane signaling: antibodies to galactocerebroside cause an influx of calcium in oligodendrocytes. Dyer, C.A., Benjamins, J.A. J. Cell Biol. (1990) [Pubmed]
  10. IL-1beta differentially regulates calcium wave propagation between primary human fetal astrocytes via pathways involving P2 receptors and gap junction channels. John, G.R., Scemes, E., Suadicani, S.O., Liu, J.S., Charles, P.C., Lee, S.C., Spray, D.C., Brosnan, C.F. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  11. Three distinct mechanisms generate oxygen free radicals in neurons and contribute to cell death during anoxia and reoxygenation. Abramov, A.Y., Scorziello, A., Duchen, M.R. J. Neurosci. (2007) [Pubmed]
  12. Cytosolic calcium staircase in cultured myocardial cells. Lee, H.C., Clusin, W.T. Circ. Res. (1987) [Pubmed]
  13. Drosophila quail, a villin-related protein, bundles actin filaments in apoptotic nurse cells. Matova, N., Mahajan-Miklos, S., Mooseker, M.S., Cooley, L. Development (1999) [Pubmed]
  14. Simultaneous measurement of stimulus-induced changes in cytoplasmic Ca2+ and in membrane potential of human neutrophils. Lazzari, K.G., Proto, P.J., Simons, E.R. J. Biol. Chem. (1986) [Pubmed]
  15. Apoptosis induced by withdrawal of interleukin-3 (IL-3) from an IL-3-dependent hematopoietic cell line is associated with repartitioning of intracellular calcium and is blocked by enforced Bcl-2 oncoprotein production. Baffy, G., Miyashita, T., Williamson, J.R., Reed, J.C. J. Biol. Chem. (1993) [Pubmed]
  16. CTL adhesion and antigen recognition are discrete steps in the human CTL-target cell interaction. Mentzer, S.J., Smith, B.R., Barbosa, J.A., Crimmins, M.A., Herrmann, S.H., Burakoff, S.J. J. Immunol. (1987) [Pubmed]
  17. Effect of ischemia on calcium-dependent fluorescence transients in rabbit hearts containing indo 1. Correlation with monophasic action potentials and contraction. Lee, H.C., Mohabir, R., Smith, N., Franz, M.R., Clusin, W.T. Circulation (1988) [Pubmed]
  18. Cellular uncoupling during ischemia in hypertrophied and failing rabbit ventricular myocardium: effects of preconditioning. Dekker, L.R., Rademaker, H., Vermeulen, J.T., Opthof, T., Coronel, R., Spaan, J.A., Janse, M.J. Circulation (1998) [Pubmed]
  19. Variability of spontaneous Ca2+ release between different rat ventricular myocytes is correlated with Na(+)-Ca2+ exchange and [Na+]i. Díaz, M.E., Cook, S.J., Chamunorwa, J.P., Trafford, A.W., Lancaster, M.K., O'Neill, S.C., Eisner, D.A. Circ. Res. (1996) [Pubmed]
  20. Neuromedin U: a Myb-regulated autocrine growth factor for human myeloid leukemias. Shetzline, S.E., Rallapalli, R., Dowd, K.J., Zou, S., Nakata, Y., Swider, C.R., Kalota, A., Choi, J.K., Gewirtz, A.M. Blood (2004) [Pubmed]
  21. On the role of voltage-dependent calcium channels in calcium signaling of astrocytes in situ. Carmignoto, G., Pasti, L., Pozzan, T. J. Neurosci. (1998) [Pubmed]
  22. Synthesis of platelet-activating factor by endothelial cells. The role of G proteins. Whatley, R.E., Fennell, D.F., Kurrus, J.A., Zimmerman, G.A., McIntyre, T.M., Prescott, S.M. J. Biol. Chem. (1990) [Pubmed]
  23. Depolarizing stimuli and neurotransmitters utilize separate pathways to activate protein kinase C in sympathetic neurons. Wakade, T.D., Bhave, S.V., Bhave, A.S., Malhotra, R.K., Wakade, A.R. J. Biol. Chem. (1991) [Pubmed]
  24. All-trans retinoic acid inhibits fluctuations in intracellular Ca2+ resulting from changes in extracellular Ca2+. Varani, J., Burmeister, B., Perone, P., Bleavins, M., Johnson, K.J. Am. J. Pathol. (1995) [Pubmed]
  25. A noninvasive fluorimetric procedure for measurement of membrane potential. Quantification of the NADPH oxidase-induced depolarization in activated neutrophils. Jankowski, A., Grinstein, S. J. Biol. Chem. (1999) [Pubmed]
  26. Cytoplasmic free calcium distributions during the development of root hairs of Arabidopsis thaliana. Wymer, C.L., Bibikova, T.N., Gilroy, S. Plant J. (1997) [Pubmed]
  27. Activation of heterologously expressed Drosophila TRPL channels: Ca2+ is not required and InsP3 is not sufficient. Hardie, R.C., Raghu, P. Cell Calcium (1998) [Pubmed]
  28. Differential regulation of Ca2+ mobilization in human thymocytes by coaggregation of surface molecules. Deusch, K., Daley, J.F., Levine, H., Languet, A.J., Anderson, P., Schlossman, S.F., Blue, M.L. J. Immunol. (1990) [Pubmed]
  29. Evidence that TRH controls prolactin release from rat lactotrophs by stimulating a calcium influx. Guérineau, N.C., Lledo, P.M., Verrier, D., Israel, J.M. Cell Biol. Toxicol. (1994) [Pubmed]
  30. Calcium channels activated by endothelin-1 in human trophoblast. Niger, C., Malassiné, A., Cronier, L. J. Physiol. (Lond.) (2004) [Pubmed]
  31. Novel glycosaminoglycan mimetic (RGTA, RGD120) contributes to enhance skeletal muscle satellite cell fusion by increasing intracellular Ca2+ and calpain activity. Zimowska, M., Constantin, B., Papy-Garcia, D., Raymond, G., Cognard, C., Caruelle, J.P., Moraczewski, J., Martelly, I. J. Cell. Physiol. (2005) [Pubmed]
  32. Heterogeneity in filamentous actin content among individual human blood platelets. Oda, A., Daley, J.F., Cabral, C., Kang, J.H., Smith, M., Salzman, E.W. Blood (1992) [Pubmed]
  33. Stimulated rise in neuronal calcium is faster and greater in the nucleus than the cytosol. Przywara, D.A., Bhave, S.V., Bhave, A., Wakade, T.D., Wakade, A.R. FASEB J. (1991) [Pubmed]
  34. Functional competency of T cell antigen receptors in human thymus. Weiss, A., Dazin, P.F., Shields, R., Fu, S.M., Lanier, L.L. J. Immunol. (1987) [Pubmed]
  35. Quantitation of cytosolic [Ca2+] in whole perfused rat hearts using Indo-1 fluorometry. Brandes, R., Figueredo, V.M., Camacho, S.A., Baker, A.J., Weiner, M.W. Biophys. J. (1993) [Pubmed]
  36. Calcium transients caused by calcium entry are influenced by the sarcoplasmic reticulum in guinea-pig atrial myocytes. Lipp, P., Pott, L., Callewaert, G., Carmeliet, E. J. Physiol. (Lond.) (1992) [Pubmed]
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