Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress

Kops, Geert J. P. L.; Dansen, Tobias B.; Polderman, Paulien E.; Saarloos, Ingrid; Wirtz, K.W.A.; Coffer, Paul J.; Huang, Ting-T.; Bos, Johannes L.; Medema, René H.; Burgering, Boudewijn M.T.

doi:10.1038/nature01036

Cited by 1,424 publications

(1,165 citation statements)

References 27 publications

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“…Nevertheless, there are also reports showing that it can inhibit apoptosis 19,44 . It stimulates the expression of the anti-apoptotic factors including manganese superoxide dismutase 48 and catalase 49 . Our present work unveils that Foxo3a can transactivate miR-484 expression.…”

Section: Discussionmentioning

confidence: 99%

miR-484 regulates mitochondrial network through targeting Fis1

et al. 2012

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mitochondria constantly undergo fusion and fission, two necessary processes for the maintenance of organelle fidelity. The abnormal mitochondrial fission participates in the pathogenesis of many diseases, but its regulation remains poorly understood. Here we show that miR-484 can suppress translation of mitochondrial fission protein Fis1, and inhibit Fis1-mediated fission and apoptosis in cardiomyocytes and in the adrenocortical cancer cells. We demonstrate that Fis1 is necessary for mitochondrial fission and apoptosis, and is upregulated during anoxia, whereas miR-484 is downregulated. miR-484 is able to attenuate Fis1 upregulation and mitochondrial fission, by binding to the amino acid coding sequence of Fis1 and inhibiting its translation. In exploring the underlying mechanism of miR-484 downregulation upon apoptosis, we observe that Foxo3a transactivates miR-484 expression. Foxo3a transgenic or knockout mice exhibit, respectively, a high or low level of miR-484 and a reduced or enhanced mitochondrial fission, apoptosis and myocardial infarction. our data reveal a model of mitochondrial fission regulation by a microRnA.

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Section: Discussionmentioning

confidence: 99%

miR-484 regulates mitochondrial network through targeting Fis1

et al. 2012

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“…As accumulation of damage caused by ROS (reactive oxygen species) was postulated to be causative for aging, it has been hypothesized that FOXO factors influence aging and age‐related diseases by increasing the antioxidant capacity of cells (Kops et al ., 2002; Storz, 2011). ROS play an important role as second messengers of cellular signaling and can lead to oxidative stress when cellular detoxification activity is decreased.…”

Section: Foxo and Resistance To Oxidative Stressmentioning

confidence: 99%

“…FOXOs are regulated by oxidative stress via changes in upstream FOXO regulatory pathways or directly sensing the cellular redox status through reversible oxidation and reduction of cystein residues (Essers et al ., 2004; Eijkelenboom & Burgering, 2013; Putker et al ., 2013). FOXO factors regulate the expression of the key detoxification enzymes MnSOD (manganese superoxide dismutase), catalase, and GADD45 (Kops et al ., 2002; Nemoto & Finkel, 2002). Accordingly, inactivation of Foxo factors has been shown to lead to intracellular accumulation of ROS promoting accelerated atherosclerosis, proliferation of transformed cells, and compromising long‐term proliferative potential of normal stem cells (Tothova et al ., 2007; Tsuchiya et al ., 2013).…”

Section: Foxo and Resistance To Oxidative Stressmentioning

confidence: 99%

Long live FOXO: unraveling the role of FOXO proteins in aging and longevity

2015

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SummaryAging constitutes the key risk factor for age‐related diseases such as cancer and cardiovascular and neurodegenerative disorders. Human longevity and healthy aging are complex phenotypes influenced by both environmental and genetic factors. The fact that genetic contribution to lifespan strongly increases with greater age provides basis for research on which “protective genes” are carried by long‐lived individuals. Studies have consistently revealed FOXO (Forkhead box O) transcription factors as important determinants in aging and longevity. FOXO proteins represent a subfamily of transcription factors conserved from Caenorhabditis elegans to mammals that act as key regulators of longevity downstream of insulin and insulin‐like growth factor signaling. Invertebrate genomes have one FOXO gene, while mammals have four FOXO genes: FOXO1, FOXO3, FOXO4, and FOXO6. In mammals, this subfamily is involved in a wide range of crucial cellular processes regulating stress resistance, metabolism, cell cycle arrest, and apoptosis. Their role in longevity determination is complex and remains to be fully elucidated. Throughout this review, the mechanisms by which FOXO factors contribute to longevity will be discussed in diverse animal models, from Hydra to mammals. Moreover, compelling evidence of FOXOs as contributors for extreme longevity and health span in humans will be addressed.

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“…3 In addition, Foxo-1 has been shown to stimulate fusion of primary mouse myoblasts to myotube and regulate various cellular functions, including cell cycle and apoptosis. [4][5][6][7][8] Another recently identified factor, GDF-8 or myostatin, has been characterized as an important and potent negative regulator of skeletal muscle growth and inhibitor of myoblast proliferation that belongs to the TGF-b family of secreted growth and differentiation factors. Mutations in the GDF-8 gene showed a marked increase in body weight and muscle mass in cattle.…”

Section: Introductionmentioning

confidence: 99%

Effect of RNA oligonucleotide targeting Foxo-1 on muscle growth in normal and cancer cachexia mice

Yang

Liu

et al. 2007

Cancer Gene Ther

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Foxo-1, a member of the Foxo forkhead type transcription factors, is markedly upregulated in skeletal muscle in energy-deprived states such as fasting, cancer and severe diabetes. In this study, we target the Foxo-1 mRNA in a mouse skeletal myoblast cell line C2C12 and in vivo models of normal and cancer cachexia mice by a Foxo-1 specific RNA oligonucleotide. Our results demonstrate that the RNA oligonucleotide can reduce the expression of Foxo-1 in cells and in normal and cachectic mice, leading to an increase in skeletal muscle mass of the mice. In search for the possible downstream target genes of Foxo-1, we show that when Foxo-1 expression is blocked both in cells and in mice, the level of MyoD, a myogenic factor, is increased while a muscle negative regulator GDF-8 or myostatin is suppressed. Taken together, these results show that Foxo-1 pays a critical role in development of muscle atrophy, and suggest that Foxo-1 is a potential molecular target for treatment of muscle wasting conditions.

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Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress

Cited by 1,424 publications

References 27 publications

miR-484 regulates mitochondrial network through targeting Fis1

miR-484 regulates mitochondrial network through targeting Fis1

Long live FOXO: unraveling the role of FOXO proteins in aging and longevity

Effect of RNA oligonucleotide targeting Foxo-1 on muscle growth in normal and cancer cachexia mice

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