Alterations in the molecular response to DNA damage during cellular aging of cultured fibroblasts: Reduced AP‐1 activation and collagenase gene expression

Choi, Augustine M.K.; Pignolo, Robert J.; Rhys, Colette M.J. ap; Cristofalo, Vincent J.; Holbrook, Nikki J.

doi:10.1002/jcp.1041640109

Cited by 28 publications

(12 citation statements)

References 40 publications

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“…c-fos loses mitogen responsiveness in senescent human fibro blasts [6,[18][19][20]. Thus, c-fos mRNA and pro tein are undetectable in senescent cells, whether or not they are stimulated by serum.…”

Section: Ap-1 Activity Is Lost Upon Cellularmentioning

confidence: 95%

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Replicative Senescence, Aging and Growth-Regulatory Transcription Factors

et al. 1996

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Normal somatic cells invariably enter a state of permanent growth arrest and altered function after a finite number of divisions. This phenomenon is termed cellular or replicative senescence. Replicative senescence is thought to be a tumor-suppressive mechanism, and a contributing factor in aging. Three features distinguish senescent from presenescent cells: an irreversible block to cell proliferation, increased resistance to apoptotic death, and changes in differentiated functions. Senescence entails an altered pattern of gene expression, much of which is due to altered transcription. At least three growth regulatory transcriptional modulators are repressed in senescent cells: the c-fos component of the API transcription factor, the Id1 and Id2 helix-loop-helix (HLH) proteins that negatively regulate basic HLH transcription factors, and the E2F-1 component of the E2F transcription factor. Failure to express any one of these modulators is very likely sufficient to arrest cell proliferation. Loss of these modulators may also explain many of the functional changes shown by senescent cells. In the case of c-fos repression, the resulting decline in AP-1 activity may be exacerbated by an altered ratio of AP-1 components to a protein known as QM or Jif. QM interacts with the c-jun component of AP-1 and suppresses AP-1 activity. We cloned QM from a senescent fibroblast cDNA library, and found that it was neither cell cycle- nor senescence-regulated. However, QM suppressed the growth of murine and human fibroblasts when overexpressed. Thus, an altered balance between positive factors (e.g., AP-1 components) and negative factors (e.g., QM) may lead to the growth arrest, as well as the changes in differentiated gene expression, that are a hallmark of senescent cells.

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Section: Ap-1 Activity Is Lost Upon Cellularmentioning

confidence: 95%

“…First, c-fos remains inducible by DNA damaging agents in senescent cells [19]. This suggests that the c-fos damage and mitogen responses are sepa rable, and only the mitogen response is blocked by senescence.…”

Section: Ap-1 Activity Is Lost Upon Cellularmentioning

confidence: 96%

Replicative Senescence, Aging and Growth-Regulatory Transcription Factors

et al. 1996

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“…A number of studies indicate that AP-1 may be involved in the pathogenesis of hyperoxic inflammatory lung injury. In rats, the level of AP-1 activity is increased in the lung upon exposure to hyperoxia [46,97]. In addition, hyperoxia-induced oncosis of MLE-12 cells is associated with a sustained activation of AP-1 [46].…”

Section: Redox Transcription Factors In Pulmonary Hyperoxic Cell Deathmentioning

confidence: 99%

Hyperoxia-induced signal transduction pathways in pulmonary epithelial cells☆

Zaher

Miller

Morrow

et al. 2007

Free Radical Biology and Medicine

120

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Mechanical ventilation with hyperoxia is necessary to treat critically ill patients. However, prolonged exposure to hyperoxia leads to the generation of excessive reactive oxygen species (ROS), which can cause acute inflammatory lung injury. One of the major effects of hyperoxia is the injury and death of pulmonary epithelium, which is accompanied by increased levels of pulmonary proinflammatory cytokines and excessive leukocyte infiltration. A thorough understanding of the signaling pathways leading to pulmonary epithelial cell injury/death may provide some insights into the pathogenesis of hyperoxia-induced acute inflammatory lung injury. This review focuses on epithelial responses to hyperoxia and some of the major factors regulating pathways to epithelial cell injury/death, and proinflammatory responses upon exposure to hyperoxia. We discuss in detail some of the most interesting players, such as, NF-κB, that can modulate both proinflammatory responses and cell injury/death of lung epithelial cells. A better appreciation for the functions of these factors will no doubt help us to delineate the pathways to hyperoxic cell death and proinflammatory responses.

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“…Quantitative and qualitative changes in the synthesis of certain proteins [5][6][7][8] suggest that both efficiency and specificity of the biochemical machinery for protein synthesis may be different in senescent cells. These changes also affect the main components of extracellular matrix (ECM), such as fibronectin [9,10] and collagen [5,11]. We have found that the biosynthesis of proteoglycans (PG) is also modified with senescence [12], since late passage HFs incorporate greater amounts of radioactivity in the large PGs of the cell layer and show a lower ratio between PGs containing dermatan sulphate (DS) and those containing heparan sulphate (HS) [12].…”

Section: Introductionmentioning

confidence: 99%

Modifications of proteoglycans secreted into the growth medium by young and senescent human skin fibroblasts

et al. 1997

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The properties of proteoglycans (PGs) secreted into the growth medium by normal young and senescent human skin fibroblasts (HFs) were investigated. In both cases, the incorporation per cell of radioactive precursors into total PGs was similar. The polysaccharide chains of PGs from young and senescent HFs were mainly represented by galactosaminoglycuronans and showed a similar range of size distribution. However, galactosaminoglycuronans of PGs secreted by senescent HFs had a lower content of unsulphated disaccharides and a lower proportion of Dglucuronosyl residues. Moreover, senescent HFs released into the growth medium higher relative amounts of small PGs with chondroitin sulphate, dermatan sulphate chains, such as decorin.

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Alterations in the molecular response to DNA damage during cellular aging of cultured fibroblasts: Reduced AP‐1 activation and collagenase gene expression

Cited by 28 publications

References 40 publications

Replicative Senescence, Aging and Growth-Regulatory Transcription Factors

Replicative Senescence, Aging and Growth-Regulatory Transcription Factors

Hyperoxia-induced signal transduction pathways in pulmonary epithelial cells☆

Modifications of proteoglycans secreted into the growth medium by young and senescent human skin fibroblasts

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