Linked Life Data

14570874

Source:http://linkedlifedata.com/resource/pubmed/id/14570874

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-1-12
pubmed:abstractText
In addition to replicative senescence, normal diploid fibroblasts undergo stress-induced premature senescence (SIPS) in response to DNA damage caused by oxidative stress or ionizing radiation (IR). SIPS is not prevented by telomere elongation, indicating that, unlike replicative senescence, it is triggered by nonspecific genome-wide DNA damage rather than by telomere shortening. ATM, the product of the gene mutated in individuals with ataxia telangiectasia (AT), plays a central role in cell cycle arrest in response to DNA damage. Whether ATM also mediates signaling that leads to SIPS was investigated with the use of normal and AT fibroblasts stably transfected with an expression vector for the catalytic subunit of human telomerase (hTERT). Expression of hTERT in AT fibroblasts resulted in telomere elongation and prevented premature replicative senescence, but it did not rescue the defect in G(1) checkpoint activation or the hypersensitivity of the cells to IR. Despite these remaining defects in the DNA damage response, hTERT-expressing AT fibroblasts exhibited characteristics of senescence on exposure to IR or H(2)O(2) in such a manner that triggers SIPS in normal fibroblasts. These characteristics included the adoption of an enlarged and flattened morphology, positive staining for senescence-associated beta-galactosidase activity, termination of DNA synthesis, and accumulation of p53, p21(WAF1), and p16(INK4A). The phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), which mediates signaling that leads to senescence, was also detected in both IR- or H(2)O(2)-treated AT and normal fibroblasts expressing hTERT. These results suggest that the ATM-dependent signaling pathway triggered by DNA damage is dispensable for activation of p38 MAPK and SIPS in response to IR or oxidative stress.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2030-7
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:14570874-Ataxia Telangiectasia, pubmed-meshheading:14570874-Cell Aging, pubmed-meshheading:14570874-Cell Cycle Proteins, pubmed-meshheading:14570874-Cells, Cultured, pubmed-meshheading:14570874-DNA Damage, pubmed-meshheading:14570874-DNA-Binding Proteins, pubmed-meshheading:14570874-Fibroblasts, pubmed-meshheading:14570874-Humans, pubmed-meshheading:14570874-Mitogen-Activated Protein Kinases, pubmed-meshheading:14570874-Oxidative Stress, pubmed-meshheading:14570874-Phosphorylation, pubmed-meshheading:14570874-Protein-Serine-Threonine Kinases, pubmed-meshheading:14570874-Radiation Tolerance, pubmed-meshheading:14570874-Signal Transduction, pubmed-meshheading:14570874-Telomerase, pubmed-meshheading:14570874-Telomere, pubmed-meshheading:14570874-Tumor Suppressor Proteins, pubmed-meshheading:14570874-p38 Mitogen-Activated Protein Kinases
pubmed:year
2004
pubmed:articleTitle
Stress-induced premature senescence in hTERT-expressing ataxia telangiectasia fibroblasts.
pubmed:affiliation
Department of Geriatric Research, National Institute for Longevity Sciences, 36-3 Gengo, Morioka, Obu 474-8522, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't