TY - JOUR AB - Anchorage of a subset of cell surface proteins in eukaryotic cells is mediated by a glycosylphosphatidylinositol (GPI) moiety covalently attached to the carboxy-terminus of the protein moiety. Experimental evidence for the potential of GPI-anchored proteins (GPI-AP) of being released from cells into the extracellular environment has been accumulating, which involves either the loss or retention of the GPI anchor. Release of GPI-AP from donor cells may occur spontaneously or in response to endogenous or environmental signals. The experimental evidence for direct insertion of exogenous GPI-AP equipped with the complete anchor structure into the outer plasma membrane bilayer leaflets of acceptor cells is reviewed as well as the potential underlying molecular mechanisms. Furthermore, promiscuous transfer of certain GPI-AP between plasma membranes of different cells in vivo under certain (patho)physiological conditions has been reported. Engineering of target cell surfaces using chimeric GPI-AP with complete GPI anchor may be useful for therapeutic applications. AU - Müller, G. C1 - 55460 C2 - 46166 CY - 2-4 Park Square, Milton Park, Abingdon Or14 4rn, Oxon, England SP - 139-156 TI - Membrane insertion and intercellular transfer of glycosylphosphatidylinositol-anchored proteins: potential therapeutic applications. JO - Arch. Physiol. Biochem. VL - 126 IS - 2 PB - Taylor & Francis Ltd PY - 2020 SN - 1381-3455 ER - TY - JOUR AB - nsulin was first discovered in extracts of vertebrate pancreas during a focused search for a therapy for diabetes. Subsequent efforts to discover and isolate a similar active principle from yeast and plants driven by the hope to identify insulin-like/mimetic molecules with critical advantages in the pharmacokinetic profile and expenditure of production compared to authentic human insulin were not successful. As a consequence, it has generally been assumed that hormones evolved exclusively during course of the evolution of vertebrate endocrine organs, implying a rather recent origin. Concomitantly, the existence and physiological role of vertebrate hormones in lower multi- and unicellular eukaryotes have remained a rather controversial subject over decades, albeit there is some evidence that hormones and hormone-binding proteins resembling those of vertebrates are expressed in fungi and yeast. Past and recent findings on the existence of insulin-like and mimetic materials, such as the glucose tolerance factor, in lower eukaryotes, in particular Neurospora crassa and yeast, will be presented. These data provide further evidence for the provocative view that the evolutionary roots of the vertebrate endocrine system may be far more ancient than is generally believed and that the identification and characterisation of insulin-like/mimetic molecules from lower eukaryotes may be useful for future drug discovery efforts. AU - Müller, G. C1 - 57953 C2 - 48013 CY - 2-4 Park Square, Milton Park, Abingdon Or14 4rn, Oxon, England SP - 420-429 TI - Insulin-like and mimetic molecules from non-mammalian organisms: Potential relevance for drug discovery. JO - Arch. Physiol. Biochem. VL - 11 IS - 5 PB - Taylor & Francis Ltd PY - 2019 SN - 1381-3455 ER - TY - JOUR AB - Context: Perivascular adipose tissue (PVAT) is suggested to impact on vascular cells via humoral factors, possibly contributing to endothelial dysfunction and atherosclerosis. Objective: To address whether the hepatokine fibroblast growth factor (FGF) 21 affects the PVAT secretome. Methods: Human perivascular (pre)adipocytes were subjected to targeted proteomics and whole-genome gene expression analysis. Results: Preadipocytes, as compared to adipocytes, secreted higher amounts of inflammatory cytokines and chemokines. Adipocytes released higher amounts of adipokines [e.g. adipisin, visfatin, dipeptidyl peptidase 4 (DPP4), leptin; p < 0.05, all]. In preadipocytes, omentin 1 release was 1.28-fold increased by FGF-21 (p < 0.05). In adipocytes, FGF-21 reduced chemerin release by 5% and enhanced DPP4 release by 1.15-fold (p < 0.05, both). FGF-21 altered the expression of four secretory genes in preadipocytes and of 18 in adipocytes (p < 0.01, all). Conclusion: The hepatokine FGF-21 exerts secretome-modulating effects in human perivascular (pre)adipocytes establishing a new liver-PVAT-blood vessel axis that possibly contributes to vascular inflammation and atherosclerosis. AU - Berti, L. AU - Hartwig, S.* AU - Irmler, M. AU - Raedle, B. AU - Siegel-Axel, D. AU - Beckers, J. AU - Lerch, S.* AU - Al-Hasani, H.* AU - Häring, H.-U. AU - Hrabě de Angelis, M. AU - Staiger, H. C1 - 49260 C2 - 41722 CY - Abingdon SP - 281-288 TI - Impact of fibroblast growth factor 21 on the secretome of human perivascular preadipocytes and adipocytes: A targeted proteomics approach. JO - Arch. Physiol. Biochem. VL - 122 IS - 5 PB - Taylor & Francis Ltd PY - 2016 SN - 1381-3455 ER -