Universität zu Köln

Dettmar, Anne K., Binder, Elisabeth, Greiner, Friederike R., Liebau, Max C., Kurschat, Christine E., Jungraithmayr, Therese C., Saleem, Moin A., Schmitt, Claus-Peter, Feifel, Elisabeth, Orth-Hoeller, Dorothea, Kemper, Markus J., Pepys, Mark, Wuerzner, Reinhard and Oh, Jun (2014). Protection of Human Podocytes from Shiga Toxin 2-Induced Phosphorylation of Mitogen-Activated Protein Kinases and Apoptosis by Human Serum Amyloid P Component. Infect. Immun., 82 (5). S. 1872 - 1880. WASHINGTON: AMER SOC MICROBIOLOGY. ISSN 1098-5522

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Abstract

Hemolytic uremic syndrome (HUS) is mainly induced by Shiga toxin 2 (Stx2)-producing Escherichia coli. Proteinuria can occur in the early phase of the disease, and its persistence determines the renal prognosis. Stx2 may injure podocytes and induce proteinuria. Human serum amyloid P component (SAP), a member of the pentraxin family, has been shown to protect against Stx2induced lethality in mice in vivo, presumably by specific binding to the toxin. We therefore tested the hypothesis that SAP can protect against Stx2-induced injury of human podocytes. To elucidate the mechanisms underlying podocyte injury in HUS-associated proteinuria, we assessed Stx2-induced activation of mitogen-activated protein kinases (MAPKs) and apoptosis in immortalized human podocytes and evaluated the impact of SAP on Stx2-induced damage. Human podocytes express Stx2-binding globotriaosylceramide 3. Stx2 applied to cultured podocytes was internalized and then activated p38 alpha MAPK and c-Jun N-terminal kinase (JNK), important signaling steps in cell differentiation and apoptosis. Stx2 also activated caspase 3, resulting in an increased level of apoptosis. Coincubation of podocytes with SAP and Stx2 mitigated the effects of Stx2 and induced upregulation of antiapoptotic Bcl2. These data suggest that podocytes are a target of Stx2 and that SAP protects podocytes against Stx2induced injury. SAP may therefore be a useful therapeutic option.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Dettmar, Anne K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Binder, Elisabeth UNSPECIFIED UNSPECIFIED UNSPECIFIED Greiner, Friederike R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Liebau, Max C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kurschat, Christine E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jungraithmayr, Therese C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Saleem, Moin A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmitt, Claus-Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Feifel, Elisabeth UNSPECIFIED UNSPECIFIED UNSPECIFIED Orth-Hoeller, Dorothea UNSPECIFIED UNSPECIFIED UNSPECIFIED Kemper, Markus J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pepys, Mark UNSPECIFIED UNSPECIFIED UNSPECIFIED Wuerzner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Oh, Jun UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-440046
DOI:	10.1128/IAI.01591-14
Journal or Publication Title:	Infect. Immun.
Volume:	82
Number:	5
Page Range:	S. 1872 - 1880
Date:	2014
Publisher:	AMER SOC MICROBIOLOGY
Place of Publication:	WASHINGTON
ISSN:	1098-5522
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENTEROHEMORRHAGIC ESCHERICHIA-COLI; ENDOPLASMIC-RETICULUM STRESS; HEMOLYTIC-UREMIC SYNDROME; C-REACTIVE PROTEIN; ACTIN CYTOSKELETON; IN-VITRO; SHIGA-TOXIN-2; LOCALIZATION; INDUCTION; VEROTOXIN Multiple languages Immunology; Infectious Diseases Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44004