Photolysis of cell-permeant caged inositol pyrophosphates controls oscillations of cytosolic calcium in a β-cell line

S. Hauke, A. K. Dutta, V. B. Eisenbeis, D. Bezold, T. Bittner, C. Wittwer, D. Thakor, I. Pavlovic, Carsten Schultz, H. J. Jessen

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Among many cellular functions, inositol pyrophosphates (PP-InsPs) are metabolic messengers involved in the regulation of glucose uptake, insulin sensitivity, and weight gain. However, their mechanisms of action are still poorly understood. So far, the influence of PP-InsPs on cellular metabolism has been studied by overexpression or knockout/inhibition of relevant metabolizing kinases (IP6Ks, PPIP5Ks). These approaches are, inter alia, limited by time-resolution and potential compensation mechanisms. Here, we describe the synthesis of cell-permeant caged PP-InsPs as tools to rapidly modulate intracellular levels of defined isomers of PP-InsPs in a genetically non-perturbed cellular environment. We show that caged prometabolites readily enter live cells where they are enzymatically converted into still inactive, metabolically stable, photocaged PP-InsPs. Upon light-triggered release of 5-PP-InsP 5 , the major cellular inositol pyrophosphate, oscillations of intracellular Ca 2+ levels in MIN6 cells were transiently reduced to spontaneously recover again. In contrast, uncaging of 1-PP-InsP 5 , a minor cellular isomer, was without effect. These results provide evidence that PP-InsPs play an active role in regulating [Ca 2+ ] i oscillations, a key element in triggering exocytosis and secretion in β-cells.

Original languageEnglish (US)
Pages (from-to)2687-2692
Number of pages6
JournalChemical Science
Volume10
Issue number9
DOIs
StatePublished - Jan 1 2019

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Diphosphates
Photolysis
Inositol
Isomers
Cells
Calcium
Enzyme inhibition
Metabolism
Phosphotransferases
Insulin
Glucose
diphosphoric acid
Compensation and Redress

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Hauke, S., Dutta, A. K., Eisenbeis, V. B., Bezold, D., Bittner, T., Wittwer, C., ... Jessen, H. J. (2019). Photolysis of cell-permeant caged inositol pyrophosphates controls oscillations of cytosolic calcium in a β-cell line. Chemical Science, 10(9), 2687-2692. https://doi.org/10.1039/c8sc03479f

Photolysis of cell-permeant caged inositol pyrophosphates controls oscillations of cytosolic calcium in a β-cell line. / Hauke, S.; Dutta, A. K.; Eisenbeis, V. B.; Bezold, D.; Bittner, T.; Wittwer, C.; Thakor, D.; Pavlovic, I.; Schultz, Carsten; Jessen, H. J.

In: Chemical Science, Vol. 10, No. 9, 01.01.2019, p. 2687-2692.

Research output: Contribution to journalArticle

Hauke, S, Dutta, AK, Eisenbeis, VB, Bezold, D, Bittner, T, Wittwer, C, Thakor, D, Pavlovic, I, Schultz, C & Jessen, HJ 2019, 'Photolysis of cell-permeant caged inositol pyrophosphates controls oscillations of cytosolic calcium in a β-cell line', Chemical Science, vol. 10, no. 9, pp. 2687-2692. https://doi.org/10.1039/c8sc03479f
Hauke, S. ; Dutta, A. K. ; Eisenbeis, V. B. ; Bezold, D. ; Bittner, T. ; Wittwer, C. ; Thakor, D. ; Pavlovic, I. ; Schultz, Carsten ; Jessen, H. J. / Photolysis of cell-permeant caged inositol pyrophosphates controls oscillations of cytosolic calcium in a β-cell line. In: Chemical Science. 2019 ; Vol. 10, No. 9. pp. 2687-2692.
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