Gunnar Mellgren

Nuclear import of glucokinase in pancreatic beta-cells is mediated by a nuclear localization signal and modulated by SUMOylation

Publisher: Elsevier BV

Date: 10-2017

DOI: 10.1016/J.MCE.2017.06.020

Abstract: The localization of glucokinase in pancreatic beta-cell nuclei is a controversial issue. Although previous reports suggest such a localization, the mechanism for its import has so far not been identified. Using immunofluorescence, subcellular fractionation and mass spectrometry, we present evidence in support of glucokinase localization in beta-cell nuclei of human and mouse pancreatic sections, as well as in human and mouse isolated islets, and murine MIN6 cells. We have identified a conserved, seven-residue nuclear localization signal (

Recent advances in early memory development: Research on typical and atypical children

Publisher: Wiley

Date: 15-01-2013

DOI: 10.1111/SJOP.12037

LC-MS/MS based profiling and dynamic modelling of the steroidogenesis pathway in adrenocarcinoma H295R cells

Publisher: Elsevier BV

Date: 10-2018

DOI: 10.1016/J.TIV.2018.07.002

Abstract: Endocrine disrupting chemicals have been reported to exert effects directly on enzymes involved in steroid biosynthesis. Here, we present a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for profiling the steroid metabolome of H295R human adrenocarcinoma cells. Our method can simultaneously analyse 19 precursors, intermediates and end-products, representing the adrenal steroid biosynthesis pathway. In order to obtain better insights into the processes of steroidogenesis, we investigated the dose-response relationship of forskolin, an activator of adenylate cyclase, on steroid production in H295R cells. We observed that 1.5 μM forskolin stimulated steroid production at approximately 50% of the maximum rate for most steroids. Hence, we studied the time course for steroid synthesis over 72 h in H295R cells that were stimulated with forskolin. At 24 h, we observed a peak in steroid levels for the intermediate metabolites, such as progesterone and pregnenolone, while end-products such as testosterone and cortisol continued to increase until 72 h. Finally, we show how global data provide a unique basis to develop a comprehensive, dynamic model for steroidogenesis using first order kinetics. The timeline data made it possible to estimate all reaction rate constants of the network. We propose this method as a unique and sensitive screening tool to identify effects on adrenal steroidogenesis by endocrine disrupting compounds.

Haukeland University Hospital

Location: Norway

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University Of Bergen

Location: Norway

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Uppsala Universitet

Location: Sweden

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Linköpings Universitet

Location: Sweden

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