TY  - GEN
A1  - Nojima, Hiroyuki
A1  - Konishi, Takanori
A1  - Freeman, Christopher M.
A1  - Schuster, Rebecca M.
A1  - Japtok, Lukasz
A1  - Kleuser, Burkhard
A1  - Edwards, Michael J.
A1  - Gulbins, Erich
A1  - Lentsch, Alex B.
T1  - Chemokine receptors, CXCR1 and CXCR2, differentially regulate exosome release in hepatocytes
T2  - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2  - Exosomes are small membrane vesicles released by different cell types, including hepatocytes, that play important roles in intercellular communication. We have previously demonstrated that hepatocyte-derived exosomes contain the synthetic machinery to form sphingosine-1-phosphate (S1P) in target hepatocytes resulting in proliferation and liver regeneration after ischemia/reperfusion (I/R) injury. We also demonstrated that the chemokine receptors, CXCR1 and CXCR2, regulate liver recovery and regeneration after I/R injury. In the current study, we sought to determine if the regulatory effects of CXCR1 and CXCR2 on liver recovery and regeneration might occur via altered release of hepatocyte exosomes. We found that hepatocyte release of exosomes was dependent upon CXCR1 and CXCR2. CXCR1-deficient hepatocytes produced fewer exosomes, whereas CXCR2-deficient hepatocytes produced more exosomes compared to their wild-type controls. In CXCR2-deficient hepatocytes, there was increased activity of neutral sphingomyelinase (Nsm) and intracellular ceramide. CXCR1-deficient hepatocytes had no alterations in Nsm activity or ceramide production. Interestingly, exosomes from CXCR1-deficient hepatocytes had no effect on hepatocyte proliferation, due to a lack of neutral ceramidase and sphingosine kinase. The data demonstrate that CXCR1 and CXCR2 regulate hepatocyte exosome release. The mechanism utilized by CXCR1 remains elusive, but CXCR2 appears to modulate Nsm activity and resultant production of ceramide to control exosome release. CXCR1 is required for packaging of enzymes into exosomes that mediate their hepatocyte proliferative effect.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 538 
KW  - hepatic ischemia-reperfusion
KW  - liver-regeneration
KW  - injury
KW  - ischemia/reperfusion
KW  - neutrophil
KW  - ceramide
KW  - homolog
KW  - mice
KW  - mechanisms
KW  - recovery
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-410885
SN  - 1866-8372
IS  - 538
ER  - 
TY  - GEN
A1  - Walter, Tim
A1  - Collenburg, Lena
A1  - Japtok, Lukasz
A1  - Kleuser, Burkhard
A1  - Schneider-Schaulies, Sibylle
A1  - Müller, Nora
A1  - Becam, Jerome
A1  - Schubert-Unkmeir, Alexandra
A1  - Kong, Ji Na
A1  - Bieberich, Erhard
A1  - Seibel, Jürgen
T1  - Incorporation and visualization of azido-functionalized N-oleoyl serinol in Jurkat cells, mouse brain astrocytes, 3T3 fibroblasts and human brain microvascular endothelial cells
N2  - The synthesis and biological evaluation of azido-N-oleoyl serinol is reported. It mimicks biofunctional lipid ceramides and has shown to be capable of click reactions for cell membrane imaging in Jurkat and human brain microvascular endothelial cells.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 324 
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-394960
ER  - 
TY  - GEN
A1  - Henze, Andrea
A1  - Homann, Thomas
A1  - Rohn, Isabelle
A1  - Aschner, Michael A.
A1  - Link, Christopher D.
A1  - Kleuser, Burkhard
A1  - Schweigert, Florian J.
A1  - Schwerdtle, Tanja
A1  - Bornhorst, Julia
T1  - Caenorhabditis elegans as a model system to study post-translational modifications of human transthyretin
N2  - The visceral protein transthyretin (TTR) is frequently affected by oxidative post-translational protein modifications (PTPMs) in various diseases. Thus, better insight into structure-function relationships due to oxidative PTPMs of TTR should contribute to the understanding of pathophysiologic mechanisms. While the in vivo analysis of TTR in mammalian models is complex, time- and resource-consuming, transgenic Caenorhabditis elegans expressing hTTR provide an optimal model for the in vivo identification and characterization of drug-mediated oxidative PTPMs of hTTR by means of matrix assisted laser desorption/ionization – time of flight – mass spectrometry (MALDI-TOF-MS). Herein, we demonstrated that hTTR is expressed in all developmental stages of Caenorhabditis elegans, enabling the analysis of hTTR metabolism during the whole life-cycle. The suitability of the applied model was verified by exposing worms to D-penicillamine and menadione. Both drugs induced substantial changes in the oxidative PTPM pattern of hTTR. Additionally, for the first time a covalent binding of both drugs with hTTR was identified and verified by molecular modelling.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 312 
KW  - binding
KW  - c. elegans
KW  - cells
KW  - disease
KW  - force-field
KW  - life-span
KW  - menadione
KW  - n-acetyl-cysteine
KW  - protein
KW  - s-glutathionylation
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-103674
ER  -