Changes associated with aging and replicative senescence in the regulation of transcription factor nuclear factor-κB

Helenius, Merja; Hänninen, Maarit; Lehtinen, Sanna K.; Salminen, Antero

doi:10.1042/bj3180603

Cited by 225 publications

(154 citation statements)

References 30 publications

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“…These observations suggest that NF-κB activation not only negatively, but also positively regulates apoptosis. This idea has been further strengthened by studies on NMRI mice, Wistar rats, and WI-38 fibroblasts where aging induced a strong and consistent increase in the nuclear binding activity of NF-κB (Helenius et al, 1996).…”

Section: Pro-apoptotic Activity Of Nf-κbmentioning

confidence: 96%

Nuclear Factor-κB Activation: A Question of Life or Death

Shishodia¹,

Aggarwal²

2002

BMB Reports

206

168

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Apoptosis is a mode of cell death that plays an important role in both pathological and physiological processes. Research during the last decade has delineated the entire machinery needed for cell death, and its constituents were found to pre-exist in cells. The apoptotic cascade is triggered when cells are exposed to an apoptotic stimulus. It has been known for several years that inhibitors of protein synthesis can potentiate apoptosis that is induced by cytokines and other inducers. Until 1996, it was not understood why protein synthesis inhibitors potentiate apoptosis. Then three reports appeared that suggested the role of the transcription factor NF-κB activation in protecting the cells from TNF-induced apoptosis. Since then several proteins have been identified that are regulated by NF-κB and are involved in cell survival, proliferation, and protection from apoptosis. It now seems that when a cell is attacked by an apoptotic stimulus, the cell responds first by activating anti-apoptotic mechanisms, which may or may not be followed by apoptosis. Whether or not a cell undergoes proliferation, the survival, or apoptosis, appears to involve a balance between the two mechanisms. Inhibitors of protein synthesis seem to suppress the appearance of protein that are involved in anti-apoptosis. The present review discusses how NF-κB controls apoptosis.

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Section: Pro-apoptotic Activity Of Nf-κbmentioning

confidence: 96%

Nuclear Factor-κB Activation: A Question of Life or Death

Shishodia¹,

Aggarwal²

2002

BMB Reports

206

168

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“…Recent reports demonstrated the NF-jB-dependent induction of miR-146a expression by TLR signaling (Taganov et al, 2006;Cameron et al, 2008;Lukiw et al, 2008). Although details about the mechanisms of immunosenescence have yet to be elucidated, many studies have been conducted in aged humans to establish a clear correlation between an increase in the constitutive activation of NF-jB and chronic inflammation (Helenius et al, 1996;Spencer et al, 1997;Kim et al, 2002;Sarkar & Fisher, 2006). Our studies demonstrated that an appreciable rise in miR-146a expression was correlated with an age-dependent augmentation of the binding of NF-jB p65 to the miR-146a promoter in macrophages from aged mice (Fig.…”

Section: Discussionmentioning

confidence: 99%

Dysregulated expression of miR‐146a contributes to age‐related dysfunction of macrophages

Jiang¹,

Xiang²,

Wang

et al. 2011

Aging Cell

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SummaryAge-associated immune dysfunction, characterized by increased systemic levels of cytokines, manifests as an increased susceptibility to infections. Thus, understanding these negative regulators of the immune response has paved the way to delineating signaling pathways that impact immune senescence. In the present study, we found that miR-146a, which negatively regulated the expression of IL-1b and IL-6, was highly expressed in aged mice. However, there was a lack of response to the stimulation of lipopolysaccharide (LPS) and proinflammatory cytokines in macrophages of aged mice. As a result, the negative feedback regulation loop with miR-146a involving down-regulation of inflammation factors was interrupted in aged mice. Aberrant NF-jB binding to the miR-146a promoter was demonstrated to be associated with the abnormal expression of miR-146a in aged mice. The DNA methyltransferase inhibitor (5-aza-2-deoxycytidine) and the histone deacetylase inhibitor [trichostatin A (TSA)] both significantly up-regulated miR-146a transcriptional activation by altering the DNA-binding activity of NF-jB in macrophages isolated from aged mice, which suggests that DNA methylation and histone acetylation are involved in the suppression of age-dependent miR-146a expression. Additionally, high levels of histone deacetylase (HDACs) expressions contributed to the inhibition of miR-146a expression in LPS-stimulated macrophages from aged mice in vitro. While the suppression of HDACs activities by TSA could improve LPS-induced inflammatory responses owing to up-regulation of miR-146a expression in macrophages from aged mice. These data indicate that the dysregulated expression of miR-146a results in the age-associated dysfunction of macrophages, and miR-146a may be a good target for the treatment of age-related inflammatory diseases.

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“…of three independent experiments. Note that the relative activities of the di erent constructs should not be compared, as each one of them was assayed with di erent protein amounts in order to optimally assess their respective growth factor responsiveness exhibit lower NF-kB-mediated transcriptional activity (Helenius et al, 1996). Similarly, lowered induction of NF-kB in human activated T lymphocytes was noted during aging (Trebilcock and Ponnappan, 1996).…”

Section: Of Three Independent Experimentsmentioning

confidence: 99%

Cooperation between SMAD and NF-κB in growth factor regulated type VII collagen gene expression

et al. 1999

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We have previously demonstrated that transforming growth factor-b (TGF-b) and pro-in¯ammatory cytokines, such as tumor necrosis factor-a (TNF-a) or interleukin-1b, synergistically enhance the expression of type VII collagen gene (COL7A1) in human dermal ®broblasts in culture (Mauviel et al., 1994). Recently, we identi®ed a SMAD-containing complex, rapidly induced by TGF-b and binding the region [7496/7444] of the COL7A1 promoter, responsible for COL7A1 gene transactivation (Vindevoghel et al., 1998a). In this report, we demonstrate that TGF-b and TNF-a response elements are distinct entities within the COL7A1 promoter. In particular, we demonstrate that the TNFa e ect is mediated by NF-kB1/RelA (p50/p65) and RelA/RelA (p65/p65) NF-kB complexes binding the TNF-a response element (TaRE) located in the region [7252/7230], with RelA acting as the transcriptional activator. Finally, we provide de®nitive evidence for the role of both TGF-b and TNF-a response elements as enhancer sequences, functioning in the context of a heterologous promoter in an additive manner in response to TGF-b and TNF-a. This study provides the ®rst identi®cation of a functional interaction between the two immediate-early transcription factors, SMAD and NFkB, to activate the expression of an extracellular matrixrelated gene, COL7A1.

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Changes associated with aging and replicative senescence in the regulation of transcription factor nuclear factor-κB

Cited by 225 publications

References 30 publications

Nuclear Factor-κB Activation: A Question of Life or Death

Nuclear Factor-κB Activation: A Question of Life or Death

Dysregulated expression of miR‐146a contributes to age‐related dysfunction of macrophages

Cooperation between SMAD and NF-κB in growth factor regulated type VII collagen gene expression

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