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Aluminium impacts elements of the phosphoinositide signalling pathway in neuroblastoma cells

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Abstract

Inositol phosphate formation was examined in aluminium-treated murine neuroblastoma cells labelled with [3H]-myoinositol. Employing fluoride-stimulated intact cells, aluminium (0.2μM to 1 mM) reduced inositol phosphate formation in a dose-dependent manner. In digitonin-permeabilized cells, stimulated with nonhydrolyzable GTP[S], inositol phosphate formation was also inhibited by increasing aluminium doses; the IC50 value was about 20μM aluminium, while the inositol phosphate level was reduced 2.5 to 3 fold by 50μM aluminium. The inhibitory effect of aluminium (50μM) could not be reversed by increasing GTP[S] concentrations up to 500μM. Prechelation of aluminium to citrate or EGTA completely abolished the aluminium-triggered inhibition of fluoride-stimulated inositol phosphate formation in intact cells, but had little effect on the inhibition of permeabilized cells stimulated with GTP[S]. In neuroblastoma cells phosphoinositide hydrolysis could be evoked either through a pathway involving the Mg2+/guanine nucleotide binding (Gp) protein, or via a pathway operative in the presence of high intracellular Ca2+ concentrations. In the Mg2+/Gp protein-mediated pathway, formation of inositol triphosphate, IP3, inositol diphosphate, IP2, and inositol monophosphate, IP, was apparently inhibited by aluminium in an interdependent manner. As to the Ca2+-mediated pathway, aluminium application mainly diminished the release of IP3. Following interiorization, aluminium thus acts upon elements critical for phosphoinositide-associated signal transduction. An aluminium target apparently resides on the Gp protein. Phosphatidylinositol-4,5-diphosphate-specific phospholipase C probably harbours a second aluminium target.

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Authors and Affiliations

  1. Department of Microbiology and Pesticide Research Center, Michigan State University, East Lansing, Michigan, USA

    Biao Shi & Alfred Haug

  2. Department of Animal Science, Michigan State University, East Lansing, Michigan, USA

    Karen Chou

Authors
  1. Biao Shi
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  2. Karen Chou
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  3. Alfred Haug
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Shi, B., Chou, K. & Haug, A. Aluminium impacts elements of the phosphoinositide signalling pathway in neuroblastoma cells. Mol Cell Biochem 121, 109–118 (1993). https://doi.org/10.1007/BF00925969

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  • DOI: https://doi.org/10.1007/BF00925969

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