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Cationic Europium Complexes for Visualizing Fluctuations in Mitochondrial ATP Levels in Living Cells.
Mailhot, Romain; Traviss-Pollard, Thomas; Pal, Robert; Butler, Stephen J.
Afiliação
  • Mailhot R; Department of Chemistry, Loughborough University, Epinal Way, Loughborough, LE11 3TU, UK.
  • Traviss-Pollard T; Department of Chemistry, Loughborough University, Epinal Way, Loughborough, LE11 3TU, UK.
  • Pal R; Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, UK.
  • Butler SJ; Department of Chemistry, Loughborough University, Epinal Way, Loughborough, LE11 3TU, UK.
Chemistry ; 24(42): 10745-10755, 2018 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-29761917
ABSTRACT
The ability to study cellular metabolism and enzymatic processes involving adenosine triphosphate (ATP) is impeded by the lack of imaging probes capable of signalling the concentration and distribution of intracellular ATP rapidly, with high sensitivity. We report here the first example of a luminescent lanthanide complex capable of visualizing changes in the concentration of ATP in the mitochondria of living cells. Four cationic europium(III) complexes [Eu.1-4]+ have been synthesized and their binding capabilities towards nucleoside polyphosphate anions examined in aqueous solution at physiological pH. Complexes [Eu.1]+ and [Eu.3]+ bearing hydrogen bond donor groups in the pendant arms showed excellent discrimination between ATP, ADP and monophosphate species. Complex [Eu.3]+ showed relatively strong binding to ATP (logKa =5.8), providing a rapid, long-lived luminescent signal that enabled its detection in a highly competitive aqueous medium containing biologically relevant concentrations of Mg2+ , ADP, GTP, UTP and human serum albumin. This EuIII complex responds linearly to ATP within the physiological concentration range (1-5 mm), and was used to continuously monitor the apyrase-catalyzed hydrolysis of ATP to ADP in vitro. We demonstrate that [Eu.3]+ can permeate mammalian (NIH-3T3) cells efficiently and localize to the mitochondria selectively, permitting real-time visualization of elevated mitochondrial ATP levels following treatment with a broad spectrum kinase inhibitor, staurosporine, as well as depleted ATP levels upon treatment with potassium cyanide under glucose starvation conditions.
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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Apirase / Antígenos CD / Trifosfato de Adenosina / Európio / Íons / Mitocôndrias Limite: Animais / Humanos Idioma: Inglês Revista: Chemistry Assunto da revista: Química Ano de publicação: 2018 Tipo de documento: Artigo País de afiliação: Reino Unido