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Article: Fluorescent analogs of NAADP with calcium mobilizing activity

TitleFluorescent analogs of NAADP with calcium mobilizing activity
Authors
Issue Date1998
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/bbagen
Citation
Biochimica Et Biophysica Acta - General Subjects, 1998, v. 1425 n. 1, p. 263-271 How to Cite?
AbstractNicotinic acid adenine dinucleotide phosphate (NAADP) mobilizes Ca2+ through a mechanism totally independent of cyclic ADP-ribose or inositol trisphosphate. Fluorescent analogs of NAADP were synthesized in this study to facilitate further characterization of this novel Ca2+ release mechanism. The base-exchange reaction catalyzed by ADP-ribosyl cyclase was utilized to convert nicotinamide 1,N6-ethenoadenine dinucleotide phosphate to a fluorescent product, nicotinic acid 1,N6-ethenoadenine dinucleotide phosphate (etheno-NAADP). The excitation spectrum of the product showed two maxima at 275 nm and 300 nm and an emission maximum at 410 nm. An aza derivative of etheno-NAADP was also synthesized by sequential treatments with NaOH and nitrite. The product, nicotinic acid 1,N6-etheno-2-aza-adenine dinucleotide phosphate (etheno-aza-NAADP) had excitation maxima at 280 nm and 360 nm and an emission maximum at 470 nm. The fluorescence of both analogs was sensitive to polarity and exhibited a 3-4-fold enhancement going from an aqueous buffer to an organic solvent. Proton-NMR measurements confirmed the presence of the etheno ring in both analogs. In the aza derivative the proton at the 2-position of the adenine ring was absent, consistent with the conversion of the 2-carbon to a nitrogen. Both analogs could activate Ca2+ release from sea urchin egg homogenates and the half-maximal concentrations for etheno-aza-NAADP and etheno-NAADP were at about 2.5 μM and 5 μM, respectively. At sub-threshold concentrations, both analogs could also function as antagonists, inactivating the NAADP-sensitive Ca2+ release with a half-maximal concentration of 60-80 nM. Microinjection of etheno-aza-NAADP into live eggs activated Ca2+ increase and triggered a cortical exocytotic reaction confirming its effectiveness in vivo. These fluorescent analogs are potentially useful for visualizing the novel Ca2+ stores that are sensitive to NAADP in live cells. Copyright (C) 1998 Elsevier Science B.V.
Persistent Identifierhttp://hdl.handle.net/10722/171657
ISSN
2015 Impact Factor: 5.083
2015 SCImago Journal Rankings: 2.128
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLee, HCen_US
dc.contributor.authorAarhus, Ren_US
dc.date.accessioned2012-10-30T06:16:12Z-
dc.date.available2012-10-30T06:16:12Z-
dc.date.issued1998en_US
dc.identifier.citationBiochimica Et Biophysica Acta - General Subjects, 1998, v. 1425 n. 1, p. 263-271en_US
dc.identifier.issn0304-4165en_US
dc.identifier.urihttp://hdl.handle.net/10722/171657-
dc.description.abstractNicotinic acid adenine dinucleotide phosphate (NAADP) mobilizes Ca2+ through a mechanism totally independent of cyclic ADP-ribose or inositol trisphosphate. Fluorescent analogs of NAADP were synthesized in this study to facilitate further characterization of this novel Ca2+ release mechanism. The base-exchange reaction catalyzed by ADP-ribosyl cyclase was utilized to convert nicotinamide 1,N6-ethenoadenine dinucleotide phosphate to a fluorescent product, nicotinic acid 1,N6-ethenoadenine dinucleotide phosphate (etheno-NAADP). The excitation spectrum of the product showed two maxima at 275 nm and 300 nm and an emission maximum at 410 nm. An aza derivative of etheno-NAADP was also synthesized by sequential treatments with NaOH and nitrite. The product, nicotinic acid 1,N6-etheno-2-aza-adenine dinucleotide phosphate (etheno-aza-NAADP) had excitation maxima at 280 nm and 360 nm and an emission maximum at 470 nm. The fluorescence of both analogs was sensitive to polarity and exhibited a 3-4-fold enhancement going from an aqueous buffer to an organic solvent. Proton-NMR measurements confirmed the presence of the etheno ring in both analogs. In the aza derivative the proton at the 2-position of the adenine ring was absent, consistent with the conversion of the 2-carbon to a nitrogen. Both analogs could activate Ca2+ release from sea urchin egg homogenates and the half-maximal concentrations for etheno-aza-NAADP and etheno-NAADP were at about 2.5 μM and 5 μM, respectively. At sub-threshold concentrations, both analogs could also function as antagonists, inactivating the NAADP-sensitive Ca2+ release with a half-maximal concentration of 60-80 nM. Microinjection of etheno-aza-NAADP into live eggs activated Ca2+ increase and triggered a cortical exocytotic reaction confirming its effectiveness in vivo. These fluorescent analogs are potentially useful for visualizing the novel Ca2+ stores that are sensitive to NAADP in live cells. Copyright (C) 1998 Elsevier Science B.V.en_US
dc.languageengen_US
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/bbagenen_US
dc.relation.ispartofBiochimica et Biophysica Acta - General Subjectsen_US
dc.subject.meshAdp-Ribosyl Cyclaseen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAntigens, Cden_US
dc.subject.meshAntigens, Cd38en_US
dc.subject.meshAntigens, Differentiation - Metabolismen_US
dc.subject.meshCalcium - Metabolismen_US
dc.subject.meshFemaleen_US
dc.subject.meshFluorescent Dyes - Chemistryen_US
dc.subject.meshIon Transport - Drug Effectsen_US
dc.subject.meshMagnetic Resonance Spectroscopyen_US
dc.subject.meshNad+ Nucleosidase - Metabolismen_US
dc.subject.meshNadp - Analogs & Derivatives - Chemistry - Pharmacologyen_US
dc.subject.meshOvum - Drug Effects - Metabolismen_US
dc.subject.meshSea Urchinsen_US
dc.subject.meshSpectrometry, Fluorescenceen_US
dc.titleFluorescent analogs of NAADP with calcium mobilizing activityen_US
dc.typeArticleen_US
dc.identifier.emailLee, HC:leehc@hku.hken_US
dc.identifier.authorityLee, HC=rp00545en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/S0304-4165(98)00079-8en_US
dc.identifier.pmid9813359-
dc.identifier.scopuseid_2-s2.0-0032538101en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0032538101&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume1425en_US
dc.identifier.issue1en_US
dc.identifier.spage263en_US
dc.identifier.epage271en_US
dc.identifier.isiWOS:000076324900028-
dc.publisher.placeNetherlandsen_US
dc.identifier.scopusauthoridLee, HC=26642959100en_US
dc.identifier.scopusauthoridAarhus, R=6701339421en_US

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