Quick Search:

uzh logo
Browse by:

Zurich Open Repository and Archive

Maintenance: Tuesday, July the 26th 2016, 07:00-10:00

ZORA's new graphical user interface will be relaunched (For further infos watch out slideshow ZORA: Neues Look & Feel). There will be short interrupts on ZORA Service between 07:00am and 10:00 am. Please be patient.

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-39491

Schwer, C I; Stoll, P; Pietsch, U; Stein, P; Laqua, J; Goebel, U; Hoetzel, A; Schmidt, R (2010). Up-regulation of heme oxygenase-1 by sevoflurane is not dependent on Kupffer cells and associates with ERK1/2 and AP-1 activation in the rat liver. International Journal of Biochemistry & Cell Biology, 42(11):1876-1883.

[img] PDF - Registered users only
View at publisher


Sevoflurane is a potent non-toxic inducer of the hepatoprotective enzyme heme oxygenase-1 (HO-1). So far, little is known about the underlying molecular mechanism. Therefore the aim of this study was to characterize the respective signal transduction pathway and in particular to elucidate the role of Kupffer cells in this context. Rats were treated with or without sevoflurane. The effects on hepatic HO-1 gene expression, mitogen-activated protein kinases and transcription factors were studied by Northern and Western blot analyses, immunostaining, electrophoretic mobility shift assays, and enzymatic activity assays. Kupffer cells were depleted by administration of clodronate liposomes in vivo to characterize their role in HO-1 signal transduction. In additional in vitro experiments, HO-1 mRNA expression in primary rat hepatocytes and HepG2 cells was assessed. Sevoflurane up-regulated HO-1 gene expression in pericentral hepatocytes and increased HO enzyme activity in vivo. This was associated with activation of ERK1/2 and activator protein-1. We identified c-jun/AP-1, JunD, c-fos, and Fra-1 as active subunits of the activator protein-1 complex. Administration of clodronate liposomes to rats led to depletion of Kupffer cells without affecting sevoflurane induced HO-1 expression. Moreover, sevoflurane up-regulated HO-1 mRNA in primary rat hepatocytes but not in HepG2 cells. Our results suggest that sevoflurane induced HO-1 gene expression in pericentral hepatocytes does not depend on Kupffer cells and is associated with activation of ERK1/2 and activator protein-1. Since we could recently demonstrate significant hepatoprotective effects of HO-1 induced by isoflurane, the present results may help to establish new concepts in hepatic organ protection.


3 citations in Web of Science®
4 citations in Scopus®
Google Scholar™



1 download since deposited on 17 Jan 2011
0 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Anesthesiology
Dewey Decimal Classification:610 Medicine & health
Deposited On:17 Jan 2011 13:06
Last Modified:05 Apr 2016 14:26
Publisher DOI:10.1016/j.biocel.2010.08.005
PubMed ID:20727416

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page