TY  - JOUR
A1  - Zirafi, Onofrio
A1  - Kim, Kyeong-Ae
A1  - Ständker, Ludger
A1  - Mohr, Katharina B.
A1  - Sauter, Daniel
A1  - Heigele, Anke
A1  - Kluge, Silvia F.
A1  - Wiercinska, Eliza
A1  - Chudziak, Doreen
A1  - Richter, Rudolf
A1  - Möpps, Barbara
A1  - Gierschik, Peter
A1  - Vas, Virag
A1  - Geiger, Hartmut
A1  - Lamla, Markus
A1  - Weil, Tanja
A1  - Burster, Timo
A1  - Zgraja, Andreas
A1  - Daubeuf, Francois
A1  - Frossard, Nelly
A1  - Hachet-Haas, Muriel
A1  - Heunisch, Fabian
A1  - Reichetzeder, Christoph
A1  - Galzi, Jean-Luc
A1  - Perez-Castells, Javier
A1  - Canales-Mayordomo, Angeles
A1  - Jimenez-Barbero, Jesus
A1  - Gimenez-Gallego, Guillermo
A1  - Schneider, Marion
A1  - Shorter, James
A1  - Telenti, Amalio
A1  - Hocher, Berthold
A1  - Forssmann, Wolf-Georg
A1  - Bonig, Halvard
A1  - Kirchhoff, Frank
A1  - Münch, Jan
T1  - Discovery and Characterization of an Endogenous CXCR4 Antagonist
JF  - Cell reports
N2  - CXCL12-CXCR4 signaling controls multiple physiological processes and its dysregulation is associated with cancers and inflammatory diseases. To discover as-yet-unknown endogenous ligands of CXCR4, we screened a blood-derived peptide library for inhibitors of CXCR4-tropic HIV-1 strains. This approach identified a 16 amino acid fragment of serum albumin as an effective and highly specific CXCR4 antagonist. The endogenous peptide, termed EPI-X4, is evolutionarily conserved and generated from the highly abundant albumin precursor by pH-regulated proteases. EPI-X4 forms an unusual lasso-like structure and antagonizes CXCL12-induced tumor cell migration, mobilizes stem cells, and suppresses inflammatory responses in mice. Furthermore, the peptide is abundant in the urine of patients with inflammatory kidney diseases and may serve as a biomarker. Our results identify EPI-X4 as a key regulator of CXCR4 signaling and introduce proteolysis of an abundant precursor protein as an alternative concept for chemokine receptor regulation.
Y1  - 2015
U6  - https://doi.org/10.1016/j.celrep.2015.03.061
SN  - 2211-1247
VL  - 11
IS  - 5
SP  - 737
EP  - 747
PB  - Cell Press
CY  - Cambridge
ER  - 
TY  - JOUR
A1  - Tsuprykov, Oleg
A1  - Chaykovska, Lyubov
A1  - Kretschmer, Axel
A1  - Stasch, Johannes-Peter
A1  - Pfab, Thiemo
A1  - Krause-Relle, Katharina
A1  - Reichetzeder, Christoph
A1  - Kalk, Philipp
A1  - Adamski, Jerzy
A1  - Hocher, Berthold
T1  - Endothelin-1 overexpression improves renal function in eNOS knockout mice
JF  - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology
N2  - Background/Aims: To investigate the renal phenotype under conditions of an activated renal ET-1 system in the status of nitric oxide deficiency, we compared kidney function and morphology in wild-type, ET-1 transgenic (ET+/+), endothelial nitric oxide synthase knockout (eNOS-/-) and ET+/+eNOS-/- mice. Methods: We assessed blood pressure, parameters of renal morphology, plasma cystatin C, urinary protein excretion, expression of genes associated with glomerular filtration barrier and tissue remodeling, and plasma metabolites using metabolomics. Results: eNOS-/- and ET+/+eNOS-/- mice developed hypertension. Osteopontin, albumin and protein excretion were increased in eNOS-/- and restored in ET+/+eNOS-/- animals. All genetically modified mice developed renal interstitial fibrosis and glomerulosclerosis. Genes involved in tissue remodeling (serpinel, TIMP1, Collal, CCL2) were up-regulated in eNOS-/-, but not in ET+/+eNOS-/- mice. Plasma levels of free carnitine and acylcarnitines, amino acids, diacyl phosphatidylcholines, lysophosphatidylcholines and hexoses were descreased in eNOS-/- and were in the normal range in ET+/+eNOS-/- mice. Conclusion: eNOS-/- mice developed renal dysfunction, which was partially rescued by ET-1 overexpression in eNOS-/- mice. The metabolomics results suggest that ET-1 overexpression on top of eNOS knockout is associated with a functional recovery of mitochondria (rescue effect in 13-oxidation of fatty acids) and an increase in antioxidative properties (normalization of monounsaturated fatty acids levels). (C) 2015 The Author(s) Published by S. Karger AG, Basel
KW  - Chronic kidney disease
KW  - Endothelial nitric oxide synthase
KW  - Endothelin
KW  - Mice
KW  - Nitric oxide
Y1  - 2015
U6  - https://doi.org/10.1159/000438516
SN  - 1015-8987
SN  - 1421-9778
VL  - 37
IS  - 4
SP  - 1474
EP  - 1490
PB  - Karger
CY  - Basel
ER  -