c-myb has a character of oxidative stress resistance in aged human diploid fibroblasts: regulates SAPK/JNK and Hsp60 pathway consequently

Lee, Younghee; Lee, Nan-Hee; Bhattarai, Govinda; Hwang, Pyong-Han; Kim, Tae Il; Jhee, Eun-Chung; Yi, Ho-Keun

doi:10.1007/s10522-009-9244-0

Cited by 11 publications

(13 citation statements)

References 35 publications

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“…Here, the 25 transcripts associated to disease-specific CpG sites were enriched for transcription factor binding sites for MYB ( z -test; TRANSFAC: FDR < 0.05), a transcription factor associated to aging, 15 including the response to oxidative stress of aged cells 16 . It is of note that the DNA polymerase POLD3 is among the MYB targets, whose deregulation, due to its DNA repair activity, might have a direct impact on the disease phenotypes as it was observed for the DNA repair gene WRN (Fig.…”

Section: Resultsmentioning

confidence: 99%

Aberrant DNA methylation profiles in the premature aging disorders Hutchinson-Gilford Progeria and Werner syndrome

2013

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DNA methylation gradiently changes with age and is likely to be involved in aging-related processes with subsequent phenotype changes and increased susceptibility to certain diseases. The Hutchinson-Gilford Progeria (HGP) and Werner Syndrome (WS) are two premature aging diseases showing features of common natural aging early in life. Mutations in the LMNA and WRN genes were associated to disease onset; however, for a subset of patients the underlying causative mechanisms remain elusive. We aimed to evaluate the role of epigenetic alteration on premature aging diseases by performing comprehensive DNA methylation profiling of HGP and WS patients. We observed profound changes in the DNA methylation landscapes of WRN and LMNA mutant patients, which were narrowed down to a set of aging related genes and processes. Although of low overall variance, non-mutant patients revealed differential DNA methylation at distinct loci. Hence, we propose DNA methylation to have an impact on premature aging diseases.

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Section: Resultsmentioning

confidence: 99%

Aberrant DNA methylation profiles in the premature aging disorders Hutchinson-Gilford Progeria and Werner syndrome

2013

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“…23 However, it was demonstrated that c-myb increases the cell viability and decreases the apoptosisrelated signalling activation in the ageing process of human diploid fibroblast cell. 18 This shows that c-myb plays a critical role in cell proliferation or survival under inflammatory condition. Furthermore, c-myb has been shown to be essential for the proliferation and survival of human leukemia cells.…”

Section: Discussionmentioning

confidence: 96%

“…A series of studies was performed on the role of c‐myb in stress‐induced cell ageing, which also is a cause of inflammation . However, it was demonstrated that c‐myb increases the cell viability and decreases the apoptosis‐related signalling activation in the ageing process of human diploid fibroblast cell . This shows that c‐myb plays a critical role in cell proliferation or survival under inflammatory condition.…”

Section: Discussionmentioning

confidence: 99%

c-myb mediates inflammatory reaction against oxidative stress in human breast cancer cell line, MCF-7

Bhattarai

Lee

et al. 2011

Cell Biochem Funct

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Emerging evidence suggests that oncogenes play an important role in the inflammatory reactions in cancer cells, but the precise molecular and cellular mechanisms linking the oncogenes to inflammation is unclear. This study examined the contribution of proto-oncogene c-myb to inflammation in MCF-7 breast cancer cells. An inflammatory response was elicited directly by the cells using an in vitro culture system whereby the cells were exposed to H(2) O(2) . Upon exposure to H(2) O(2) , the cells showed a local inflammatory response, as evidenced by matrix metalloproteinases (MMPs) and ICAM-1 expression. Significant up-regulation of the proto-oncogene c-myb also was observed under inflammatory conditions. c-myb, overexpressed in the cells by transducing with Ad/c-myb, showed an increase in MMPs and ICAM-1 expression under H(2) O(2) stimulation. Despite H(2) O(2) stimulation, the c-myb down-regulated cells by c-myb siRNA inhibit the expression of MMPs and ICAM-1. Among the MAPKs, ERK1/2 and SAPK/JNK were activated by the H(2) O(2) treatment. Interestingly, the H(2) O(2) -induced activation of ERK1/2 and SAPK/JNK was inhibited by siRNA c-myb. These results suggest that breast cancer cells may play a significant role in sustaining and amplifying the inflammation process through the activation of c-myb, which results in the activation of the ERK1/2 and SAPK/JNK pathway. This condition highlights the potential link between inflammation and its involvement in promoting breast cancer proliferation.

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“…Senescent fibroblasts have been reported to resist apoptosis by the up-regulation of a number of anti-apoptotic genes such as survivin [6], c-myb [7], major vault protein [8], and Bcl-2 [9,10]. However, whether epigenetic mechanisms control the expression of pro- and anti-apoptotic genes in senescent fibroblasts have not been defined.…”

Section: Introductionmentioning

confidence: 99%

Histone Modifications in Senescence-Associated Resistance to Apoptosis by Oxidative Stress

et al. 2013

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Aging and age-related diseases are associated with cellular senescence that results in variable apoptosis susceptibility to oxidative stress. Although fibroblast senescence has been associated with apoptosis resistance, mechanisms for this have not been well defined. In this report, we studied epigenetic mechanisms involving histone modifications that confer apoptosis resistance to senescent human diploid fibroblasts (HDFs). HDFs that undergo replicative senescence display typical morphological features, express senescence-associated β-galactosidase, and increased levels of the tumor suppressor genes, p16, p21, and caveolin-1. Senescent HDFs are more resistant to oxidative stress (exogenous H2O2)-induced apoptosis in comparison to non-senescent (control) HDFs; this is associated with constitutively high levels of the anti-apoptotic gene, Bcl-2, and low expression of the pro-apoptotic gene, Bax. Cellular senescence is characterized by global increases in H4K20 trimethylation and decreases in H4K16 acetylation in association with increased activity of Suv420h2 histone methyltransferase (which targets H4K20), decreased activity of the histone acetyltransferase, Mof (which targets H4K16), as well as decreased total histone acetyltransferase activity. In contrast to Bax gene, chromatin immunoprecipitation studies demonstrate marked enrichment of the Bcl-2 gene with H4K16Ac, and depletion with H4K20Me3, predicting active transcription of this gene in senescent HDFs. These data indicate that both global and locus-specific histone modifications of chromatin regulate altered Bcl-2:Bax gene expression in senescent fibroblasts, contributing to its apoptosis-resistant phenotype.

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c-myb has a character of oxidative stress resistance in aged human diploid fibroblasts: regulates SAPK/JNK and Hsp60 pathway consequently

Cited by 11 publications

References 35 publications

Aberrant DNA methylation profiles in the premature aging disorders Hutchinson-Gilford Progeria and Werner syndrome

Aberrant DNA methylation profiles in the premature aging disorders Hutchinson-Gilford Progeria and Werner syndrome

c-myb mediates inflammatory reaction against oxidative stress in human breast cancer cell line, MCF-7

Histone Modifications in Senescence-Associated Resistance to Apoptosis by Oxidative Stress

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