Epigenetic enhancement of p66Shc during cellular replicative or premature senescence

Zhang, Wenjuan; Ji, Weidong; Liu, Yang; Xu, Yongqiang; Yang, Jianping; Zhuang, Zhixiong

doi:10.1016/j.tox.2010.07.011

Cited by 16 publications

(11 citation statements)

References 21 publications

(23 reference statements)

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“…On the other hand, elevation of p66Shc protein has been observed in primary human prostate tumors (Veeramani et al ., 2005), in replicative senescence (Zhang et al . 2010), in middle-aged mice (Lebiedzinska et al ., 2009), as well as in cells exposed to oxidative stress and UVC (Favetta et al ., 2004). Regulation of p66Shc at transcriptional level by p53 and DNA methylation has been described (Trinei et al ., 2002; Ventura et al ., 2002).…”

Section: Introductionmentioning

confidence: 99%

let‐7‐repressesed Shc translation delays replicative senescence

Pang

Cai

et al. 2013

Aging Cell

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Summary The p66Shc adaptor protein is an important regulator of life span in mammals, but the mechanisms responsible remain unclear. Here we show that expression of p66Shc, p52Shc, and p46Shc is regulated at the post-transcriptional level by the microRNA let-7a. The levels of let-7a correlated inversely with the levels of Shc proteins without affecting Shc mRNA levels. We identified ‘seedless’ let-7a interaction elements in the coding region (CR) of Shc mRNA; mutation of the ‘seedless’ interaction sites abolished the regulation of Shc by let-7a. Our results further revealed that repression of Shc expression by let-7a delays senescence of human diploid fibroblasts (HDFs). In sum, our findings link let-7a abundance to the expression of p66Shc, which in turn controls the replicative life span of HDFs.

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Section: Introductionmentioning

confidence: 99%

let‐7‐repressesed Shc translation delays replicative senescence

Pang

Cai

et al. 2013

Aging Cell

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“…The p66Shc increase has been described to be associated with increased histone acetylation [45], which is necessary for p66Shc transcription [22]. Promoter analysis showed that the highest transcription levels in the p66Shc promoter were localized to a region between −434 and −101 bp upstream of ATG upon transfection of cells lacking endogenous p66Shc [38].…”

Section: Discussionmentioning

confidence: 99%

“…Promoter analysis showed that the highest transcription levels in the p66Shc promoter were localized to a region between −434 and −101 bp upstream of ATG upon transfection of cells lacking endogenous p66Shc [38]. Another interesting point described in the literature is that epigenetic p66Shc gene expression regulation is modulated by histone modifications that are dependent on Sirt1 binding to the p66Shc promoter, and as a result there is an aberrant acetyl-HistoneH3 (Lys9) expression [45]. In addition, it has been shown that SIRT1 affects the p66Shc promoter in hyperglycemia-induced endothelial dysfunction through histone H3 modification [50].…”

Section: Discussionmentioning

confidence: 99%

“…Chromatin immunoprecipitation (ChIP) analyses were performed as previously described using a transcription factor ChIP kit, in accordance with the instructions provided by the vendor (Diagenode, USA) [45]. Rabbit polyclonal antibodies against anti-acetyl-Histone H3 and SIRT1, as well as normal mouse IgG (control), were used for DNA immunoprecipitation, as described previously [22], [45].…”

Section: Methodsmentioning

confidence: 99%

“…Rabbit polyclonal antibodies against anti-acetyl-Histone H3 and SIRT1, as well as normal mouse IgG (control), were used for DNA immunoprecipitation, as described previously [22], [45]. For accurate DNA precipitation measurements, quantitative PCR was performed using a SYBR® Green qPCR Kit (Stratagene, USA).…”

Section: Methodsmentioning

confidence: 99%

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Probucol ameliorates renal injury in diabetic nephropathy by inhibiting the expression of the redox enzyme p66Shc

et al. 2017

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AimsProbucol is an anti-hyperlipidemic agent and a potent antioxidant drug that can delay progression of diabetic nephropathy (DN) and reverses renal oxidative stress in diabetic animal models; however, the mechanisms underlying these effects remain unclear. p66Shc is a newly recognized mediator of mitochondrial ROS production in renal cells under high-glucose (HG) ambience. We previously showed that p66Shc can serve as a biomarker for renal oxidative injury in DN patients and that p66Shc up-regulation is correlated with renal damage in vivo and in vitro. Here, we determined whether probucol ameliorates renal injury in DN by inhibiting p66Shc expression.ResultsWe found that the expression of SIRT1, Ac-H3 and p66Shc in kidneys of DN patients was altered. Also, probucol reduced the levels of serum creatinine, urine protein and LDL-c and attenuated renal oxidative injury and fibrosis in STZ induced diabetic mice. In addition, probucol reversed p-AMPK, SIRT1, Ac-H3 and p66Shc expression. Correlation analyses showed that p66Shc expression was correlated with p-AMPK and Sirt1 expression and severity of renal injury. In vitro pretreatment of HK-2 cells with p-AMPK and SIRT1 siRNA negated the beneficial effects of probucol. Furthermore, we noted that probucol activates p-AMPK and Sirt1 and inhibits p66shc mRNA transcription by facilitating the binding of Sirt1 to the p66Shc promoter and modulation of Ac-H3 expression in HK-2 cells under HG ambience.Innovation and conclusionOur results suggest for the first time that probucol ameliorates renal damage in DN by epigenetically suppressing p66Shc expression via the AMPK-SIRT1-AcH3 pathway.

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mRNA methylation in cell senescence

et al. 2019

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Cellular senescence, a developmental program central to normal aging and aging pathologies, is robustly regulated at the post-transcriptional level. This regulation involves the interaction of RNA-binding proteins and noncoding RNAs with senescence-associated messenger RNAs (mRNAs). There is increasing evidence that these associations are modulated by chemical modifications of specific mRNA nucleotides which can enhance or reduce the binding of regulatory factors. Recent technological advances in mass spectrometry, next-generation sequencing, and genome mapping have improved markedly the detection of mRNA modifications.Given the rising interest in the epitranscriptomic control of gene expression in aging, we discuss our incipient understanding of the chemical mRNA modifications, specifically m 6 A and m 5 C, that influence cellular senescence. This article is categorized under: RNA Export and Localization > RNA Localization RNA Processing > RNA Editing and Modification K E Y W O R D S 5-methylcytosine, aging, mRNA modifications, N 6 -methyladenosine, senescence

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Epigenetic enhancement of p66Shc during cellular replicative or premature senescence

Cited by 16 publications

References 21 publications

let‐7‐repressesed Shc translation delays replicative senescence

let‐7‐repressesed Shc translation delays replicative senescence

Probucol ameliorates renal injury in diabetic nephropathy by inhibiting the expression of the redox enzyme p66Shc

mRNA methylation in cell senescence

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