Effect of the Tumor Promoter Phorbol 12-Myristate 13-Acetate (PMA) on Proliferation of Young and Senescent WI-38 Human Diploid Fibroblasts

Tata, Vincenzo De; Ptasznik, Andrzej; Cristofalo, V. J.

doi:10.1006/excr.1993.1085

Cited by 41 publications

(13 citation statements)

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“…In response to serum, senescent HDFs fail to increase expression of c-fos, but show normal induction of c-myc, c-jun, and jun B compared with low-passage quiescent cells (Seshadri and Campisi, 1990;Riabowol et al, 1992). Age-dependent changes in signal transduction pathways in senescent fibroblasts that may contribute to the c-fos induction deficit include hyperphosphorylation of SRF, associated with a decrease in its ability to bind to the serum response element (Atadja et al, 1994), evidence of reduced activation of protein kinase C (DeTata et al, 1993;Venable et al, 1994), and altered phosphorylation and presumptive activation of MAP kinase (Afshari et al, 1993) in response to serum. Because similar mechanisms are likely to be involved in the regulation of c-fos in brain, some of these same processes may be involved in the altered c-fos regulation observed in old hippocampal neurons in the present experiment.…”

Section: Discussionmentioning

confidence: 99%

Selective Alteration of Long-Term Potentiation-Induced Transcriptional Response in Hippocampus of Aged, Memory-Impaired Rats

Lanahan¹,

Lyford²,

Stevenson

et al. 1997

J. Neurosci.

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Normal human aging is associated with selective changes in cognition that are attributable, in part, to dysfunction of hippocampal pathways. Rodents also exhibit age-dependent hippocampal dysfunction that results in spatial memory deficits and a correlated reduction in the maintenance of long-term potentiation (LTP). Although suprathreshold stimulus protocols result in normal LTP induction in aged rats, the ability to sustain this increase in synaptic efficacy is reduced in the old animals. The maintenance phase of LTP is known to be dependent on rapid, transcriptional events, and recent studies have identified signal transduction mechanisms that link glutamate-induced responses at the synapse with transcriptional responses at the nucleus. To examine the integrity of these signaling pathways in aged hippocampus, we monitored the induction of a panel of immediate early genes (IEGs) that are known to be transcriptionally activated after LTP-inducing stimuli, using a "reverse Northern" strategy. Here we report that a broad representation of IEGs are similarly induced in awake, behaving young adult and aged, memory-impaired rats. This indicates a general preservation of these presumptive signaling pathways during the aging process. Induced levels of c-fos mRNA, however, are significantly higher in the aged animals. These observations suggest that age-dependent hippocampal dysfunction may be associated with a selective change in the dynamic activity of signaling pathways upstream of c-fos, possibly involving calcium regulation.

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Section: Discussionmentioning

confidence: 99%

Selective Alteration of Long-Term Potentiation-Induced Transcriptional Response in Hippocampus of Aged, Memory-Impaired Rats

Lanahan¹,

Lyford²,

Stevenson

et al. 1997

J. Neurosci.

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“…This inactivation of PKC results in a failure to induce AP-1 downstream 3 ; an effect that is also observed in senescence. 5 Therefore, ceramide inhibition of proliferation is affected, in part, by acting on the PLD/diacylglycerol/PKC pathway. 3,6 Ceramide is a metabolic intermediate and a signaling molecule.…”

Section: Introductionmentioning

confidence: 99%

Ceramide induces endothelial cell senescence

Venable

Yin

2009

Cell Biochemistry & Function

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Ceramide has been proposed to be a mediator of replicative senescence. Our aim was to determine whether ceramide induces senescence in vascular endothelial cells. Human umbilical vein endothelial cells were cultured to different population doubling levels and ceramide levels were quantitated. The endogenous levels of ceramide increased 2.4-fold with senescence onset. Low passage cells were chronically treated with exogenous C(6)-ceramide. This treatment induced a senescent phenotype as measured by an inhibition of cell proliferation and DNA replication while increasing senescence-associated beta-galactosidase expression. This is the second cell type in which ceramide induces senescence, thus implicating ceramide as a general mediator of cellular senescence.

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“…Each outcome depends on the cellular context, the originating signal and the particular isoform activated (Dempsey et al, 2000). Altered PKC activity has been observed in senescent fibroblasts where a change in serum-induced translocation of PKC from the cytosol to the plasma membrane was reported (De Tata et al, 1993). In contrast, exogenously added phorbol 12-myristate 13-acetate (PMA, a DAG analog) stimulated this translocation identically in young and old cells, implying that the difference in response to serum was due to changes in the production of DAG (De Tata et al, 1993).…”

Section: Protein Kinase C Activity During Senescencementioning

confidence: 99%

“…Altered PKC activity has been observed in senescent fibroblasts where a change in serum-induced translocation of PKC from the cytosol to the plasma membrane was reported (De Tata et al, 1993). In contrast, exogenously added phorbol 12-myristate 13-acetate (PMA, a DAG analog) stimulated this translocation identically in young and old cells, implying that the difference in response to serum was due to changes in the production of DAG (De Tata et al, 1993). A similar differential response to serum vs. PMA was also reported for the induction of the cfos gene (Riabowol et al, 1992).…”

Section: Protein Kinase C Activity During Senescencementioning

confidence: 99%

Caveolar Vesicles in Cellular Senescence

Wheaton¹

2012

Senescence

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Effect of the Tumor Promoter Phorbol 12-Myristate 13-Acetate (PMA) on Proliferation of Young and Senescent WI-38 Human Diploid Fibroblasts

Cited by 41 publications

References 0 publications

Selective Alteration of Long-Term Potentiation-Induced Transcriptional Response in Hippocampus of Aged, Memory-Impaired Rats

Selective Alteration of Long-Term Potentiation-Induced Transcriptional Response in Hippocampus of Aged, Memory-Impaired Rats

Ceramide induces endothelial cell senescence

Caveolar Vesicles in Cellular Senescence

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