Dibutyryl-cAMP up-regulates nur77 expression via histone modification during neurite outgrowth in PC12 cells

Maruoka, Hiroki; Sasaya, Harue; Shimamura, Yuichi; Nakatani, Yosuke; Shimoke, Koji; Ikeuchi, Toshihiko

doi:10.1093/jb/mvq036

Cited by 30 publications

(30 citation statements)

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“…24 As Bim is critical for the killing of thymocytes by diverse apoptotic stimuli, 11 we tested whether thymocytes could upregulate Bim in response to catecholamines. Treatment of thymocytes in foetal thymic organ culture (FTOC) with isoproterenol resulted in a robust induction of Nur77, a marker for PKA activation 25 and Bim, whereas the expression of other BH3-only genes, such as Puma (Bbc3) and Noxa remained unchanged (Figure 1c).…”

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confidence: 99%

CREB-binding protein (CBP) regulates β-adrenoceptor (β-AR)−mediated apoptosis

et al. 2013

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Catecholamines regulate the b-adrenoceptor/cyclic AMP-regulated protein kinase A (cAMP/PKA) pathway. Deregulation of this pathway can cause apoptotic cell death and is implicated in a range of human diseases, such as neuronal loss during aging, cardiomyopathy and septic shock. The molecular mechanism of this process is, however, only poorly understood. Here we demonstrate that the b-adrenoceptor/cAMP/PKA pathway triggers apoptosis through the transcriptional induction of the pro-apoptotic BH3-only Bcl-2 family member Bim in tissues such as the thymus and the heart. In these cell types, the catecholamine-mediated apoptosis is abrogated by loss of Bim. Induction of Bim is driven by the transcriptional co-activator CBP (CREB-binding protein) together with the proto-oncogene c-Myc. Association of CBP with c-Myc leads to altered histone acetylation and methylation pattern at the Bim promoter site. Our findings have implications for understanding pathophysiology associated with a deregulated neuroendocrine system and for developing novel therapeutic strategies for these diseases. Cell Death and Differentiation (2013) 20, 941-952; doi:10.1038/cdd.2013 published online 12 April 2013 Cyclic adenosine monophosphate (cAMP) is a second messenger that is highly conserved throughout evolution. In metazoans, its primary role is to act as an intracellular carrier of metabolic information, regulating hormonal responses, 1 in triggering apoptotic cell death and in regulating ontogeny.2,3

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confidence: 99%

CREB-binding protein (CBP) regulates β-adrenoceptor (β-AR)−mediated apoptosis

et al. 2013

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“…Thus, HDAC inhibitors have been shown to induce specific genes. Previously, we reported the up-regulation of the nur77 gene, followed by histone modification via the protein kinase A signaling pathway or HDAC inhibitor-mediated molecular mechanisms, which in turn extended the neurites of PC12 cells [6,7]. These results emphasized the importance of a control mechanism for neurite outgrowth because this step is involved in the molecular mechanism following cell survival via the transduction of an action potential and release of a neurotransmitter if severe cell damage does not occur [8].…”

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confidence: 60%

Histone Deacetylase Inhibitor for Neurodegenerative Diseases: A Possible Medicinal Strategy by Prevention of ER Stress-Mediated Apoptosis and Induction of Neurite Elongation

Shimoke

Tomioka²,

Okamoto³

et al. 2013

Clinic Pharmacol Biopharmaceut

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Introductiontherapeutic strategy for neurodegenerative diseases. Neuronal Networks Transducing Centripetal or Centrifugal Stimulation via a Synaptic Connection ER Stress-mediated Apoptosis in the Neuronal NetworksApoptosis is an important process in vertebrate development. AbstractNeurite outgrowth is primarily necessary step to construct a neuronal network. If this step is collapsed, neurons are died and neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, which are known to induce endoplasmic reticulum (ER) stress-mediated apoptosis, are occurred.It has been elucidating that histone deacetylase (HDAC) plays a crucial role in the silencing of gene expression by the specific mechanisms. Thus, HDAC inhibitors have been shown to induce specific genes. We reported the upregulation of the nur77 gene, followed by histone modification via the protein kinase A signaling pathway or HDAC inhibitor-mediated molecular mechanisms. Then, we also focused on neurite outgrowth as a functional neuronal marker, and then described molecular targets and progressive pharmaceutical care for neurodegenerative disorders by using K-350. We propose that this kind of the candidate compound might contribute to build the therapeutic strategy for neurodegenerative diseases.

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“…We previously reported that PC12 cell treatment with either dbcAMP or NGF induces the expression of the immediate early gene (IEG) nur77 [20]. Since PC12 cells transition from an undifferentiated state to a differentiated state 0-4 h after treatment with K-350, PC12 cells were treated with 5 μM of K-350 for 0, 1, 2, 4 h and changes in nur77 gene expression were analyzed by RT-PCR.…”

Section: Resultsmentioning

confidence: 99%

“…It was recently demonstrated that Nur77 interacts with Bcl-2, inducing a conformational change in Bcl-2 and converting its function from a cell protective role to a more lethal role [26]. We previously reported that treatment of PC12 cells with dbcAMP induced nur77 gene expression and was associated with acetylation of histone H3 Lys14 [20]. These data suggest that nur77 is localized to the cell nucleus and functions in that compartment to promote neurite outgrowth and in contrast translocates to mitochondria in order to induce apoptosis.…”

Section: Discussionmentioning

confidence: 97%

“…We previously conducted focused research on the early phase of dibutyryl-cAMP (dbcAMP)-induced neurite outgrowth and reported that dbcAMP-induced neurite outgrowth is regulated by immediate early gene, nur77 expression in PC12 cells [20]. Results indicated that acetylation of histone H3 gradually increased during the early period of differentiation, 0-1 h after dbcAMP treatment.…”

Section: Introductionmentioning

confidence: 99%

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