Open AccessActivation of Extracellular Signal–Regulated Kinase Mediates Apoptosis Induced by UropathogenicEscherichia coliToxins via Nitric Oxide Synthase: Protective Role of Heme Oxygenase–1
Author(s) -
Ming Chen,
Wenjie Bao,
Р. И. Айзман,
Ping Huang,
Olle Aspevall,
Lars E. Gustafsson,
Sandra Ceccatelli,
Gianni Celsi
Publication year - 2004
Publication title -
the journal of infectious diseases (online. university of chicago press)/the journal of infectious diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.69
H-Index - 252
eISSN - 1537-6613
pISSN - 0022-1899
DOI - 10.1086/421243
Subject(s) - heme oxygenase , nitric oxide synthase , programmed cell death , mapk/erk pathway , biology , microbiology and biotechnology , signal transduction , kinase , protein kinase a , apoptosis , nitric oxide , heme , biochemistry , endocrinology , enzyme
Pyelonephritis is a risk factor for renal tubular epithelial cell damage in children. The inter- and intracellular regulator nitric oxide (NO) plays a role in the modulation of cellular viability in urinary tract infections, but the role of the NO pathway in renal proximal tubular-cell death remains unclear. The present study demonstrates that, in renal epithelial cells undergoing death mediated by Escherichia coli strain ARD6 serotype O6K13H1 (O6), levels of the phosphorylated extracellular signal-regulated kinase (ERK) 1/2 and inducible NO synthase (iNOS) proteins are up-regulated, but levels of endothelial NO synthase are down-regulated. When NO synthase (NOS) activity is inhibited by the specific inhibitor of NOS or mitogen-activated protein kinase kinase, cells are prevented from death. Moreover, down-regulating protein 53 (p53) does not prevent the cells from dying, although p53 is up-regulated in O6-exposed cells. Up-regulation of heme oxygenase (HO)-1 by sodium nitroprusside or by the specific activator hemin inhibits cell death. In conclusion, the activation of ERK mediates O6 toxin-mediated renal cell death via induction of iNOS. Stimulation of HO-1 protects cells against death.