Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-7-11
pubmed:abstractText
Fas, (APO-1/CD95), a transmembrane glycoprotein belonging to the tumor necrosis (TNF) receptor superfamily, transduces apoptotic death upon crosslinking by its cognate ligand (FasL). As upregulation of Fas/FasL expression occurs in neuropathological conditions (e.g., stroke, central nervous system [CNS] trauma and seizures) associated with oxidative damage, we questioned whether reactive oxygen species (ROS) can directly affect Fas and FasL expression in neuronal cells. Utilizing rat PC12 cells neuronally differentiated with nerve growth factor (NGF), we observed that concentrations of H(2)O(2) inducing apoptotic cell death rapidly trigger the expression of Fas mRNA and protein as well as FasL mRNA. Although NGF-addition to naive PC12 downregulated constitutive Fas and FasL transcription, the H(2)O(2)-induced Fas and FasL mRNA upregulation invariably occurred either in the presence or in the absence of NGF. Similarly, phorbol 1,2-myristate 1, 3-acetate (PMA), a potent protein kinase C (PKC) activator, did not modify Fas and FasL mRNA upregulation subsequent to H(2)O(2) exposure. On the contrary, forskolin and dibutyryl cAMP, which elevate intracellular cAMP by independent mechanisms, both counteracted H(2)O(2)-induced Fas, but not FasL, mRNA upregulation and increased constitutive expression of FasL mRNA. Altogether, our data show that oxidative stress is a major stimulus in eliciting Fas and FasL expression in NGF-differentiated PC12 cells. Moreover, we describe here for the first time the existence of cAMP-dependent mechanism(s) modulating Fas and FasL expression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0360-4012
pubmed:author
pubmed:copyrightInfo
Copyright 2002 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
69
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
178-88
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
H(2)O(2) induces upregulation of Fas and Fas ligand expression in NGF-differentiated PC12 cells: modulation by cAMP.
pubmed:affiliation
Research and Innovation Company, Padova, Italy. facchinetti@researchinnovation.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't