Linked Life Data

14757197

Source:http://linkedlifedata.com/resource/pubmed/id/14757197

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2004-2-3
pubmed:abstractText
Adenosine has been previously shown to be a cytoprotective paracrine released by injured cells. However, it is presently unknown whether extracellular adenosine can prevent DNA damage. We show here that the adenosine analog, 2-chloroadenosine (2CA), has a potent (IC(50)=2.04 x 10(-9)M) genoprotective effect in cells subsequently exposed to H(2)O(2). The genoprotective signaling is transduced through adenosine receptors of the A2a and A2b subtypes. Increasing [cAMP](i) by forskolin or by cell permeable 8-br-cAMP produced a similar effect, whereas inhibiting the cAMP-mediated pathway with H-89, or increasing [nitric oxide](i) or [cGMP](i) blocked 2CA effect. Proteasomal inhibitors had no impact on 2CA signaling, while lithium chloride, an inhibitor of glycogen synthase kinase 3beta, completely blocked 2CA-induced genoprotective effect. These data indicate for the first time that extracellular adenosine protects cells against imminent oxidative DNA damage and suggest that prophylactic activation of this pathway prior to genotoxic challenges might reduce mutation rates.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0027-5107
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
546
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
93-102
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Genoprotective pathways. Part I. Extracellular signaling through G(s) protein-coupled adenosine receptors prevents oxidative DNA damage.
pubmed:affiliation
Department of Internal Medicine, University of Michigan, 5520D MSRB1, Ann Arbor, MI 48109-0680, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't