Ionizing radiation induces neuronal differentiation of Neuro-2a cells via PI3-kinase and p53-dependent pathways

Eom, Hyeon Soo; Park, Hae Ran; Jo, Sung-Kee; Kim, Young Sang; Moon, Changjong; Jung, Uhee

doi:10.3109/09553002.2015.1029595

Cited by 16 publications

(19 citation statements)

References 54 publications

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“…Downregulation of p38 MAP kinase in SOCS3 stables, which are responsive to stress stimuli indicated that SOCS3 overexpression led to survival cues in the cell . Taken together, these results indicated the prosurvival effects of SOCS3 and suggest that PI‐3‐kinase‐pAKT pathway was essential for SOCS3 mediated neurite initiation and neurite extension in PC12 cells, which is consistent with the recruitment of PI‐3‐kinase‐AKT pathway in cellular differentiation .…”

Section: Discussionsupporting

confidence: 67%

SOCS3 induces neurite differentiation and promotes neuronal cell survival

2016

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Cytokines and growth factors play an important role in neuronal survival as well as cell death. The family of suppressors of cytokine signalling (SOCS) proteins, which includes SOCS1-7 and cytokine-induced suppressor (CIS), has been shown to act as negative regulators of cytokine-induced signalling. In this report, we highlight the role of SOCS3 in regulating neuronal differentiation and survival. We observed increased SOCS3 expression upon differentiation of PC12 cells as well as neural stem cells. SOCS3 overexpression upregulated differentiation of both neural stem cells and PC12 cells even in the absence of NGF, as evidenced by enhanced neurite outgrowth and upregulation of GAP43, marker associated with neurite outgrowth. siRNA-mediated silencing of SOCS3 confirmed the potential role of SOCS3 in neuritogenesis. We observed that, SOCS3-induced neurite differentiation was mediated via the PI3 kinase pathway. Another interesting observation was that SOCS3 overexpression promoted neuronal cell survival under H2 O2 -mediated stress indicating its fundamental role in cell survival. In conclusion, our results indicate that SOCS3 promotes differentiation and survival of neural cells and could be potentially useful in future therapy for treatment of neurodegenerative disorders. © 2016 IUBMB Life, 68(6):468-476, 2016.

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Section: Discussionsupporting

confidence: 67%

SOCS3 induces neurite differentiation and promotes neuronal cell survival

2016

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“…A potential role of p53 in radiation-induced neuronal differentiation had previously also been suggested based on in vitro experiments 37,38 . We confirmed these results, and showed that irradiation of primary mouse NPCs (with 1 Gy of X-rays) diminished proliferation and induced differentiation from bipolar cells into multipolar neurons (Fig.…”

Section: Resultsmentioning

confidence: 90%

“…Radiation-induced neuronal differentiation has been demonstrated in vitro 37,38,57,58 although the underlying mechanisms remained largely unclear. To our knowledge, this is the first study demonstrating the activation of a p53-dependent transcriptional program as a mechanism to induce neuronal differentiation in vivo , although a role for p53 in cellular differentiation in vivo has been previously proposed in mammary stem cells, the airway epithelium and cancer stem cells 6 .…”

Section: Discussionmentioning

confidence: 99%

p53 drives premature neuronal differentiation in response to radiation-induced DNA damage during early neurogenesis

Mfossa

Verslegers

Verreet

et al. 2020

Preprint

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Abstractp53 regulates the cellular DNA damage response (DDR). Hyperactivation of p53 during embryonic development, however, can lead to a range of developmental defects including microcephaly. Here, we induce microcephaly by acute irradiation of mouse fetuses at the onset of neurogenesis. Besides a classical DDR culminating in massive apoptosis, we observe ectopic neurons in the subventricular zone in the brains of irradiated mice, indicative of premature neuronal differentiation. A transcriptomic study indicates that p53 activates both DDR genes and differentiation-associated genes. In line with this, mice with a targeted inactivation of Trp53 in the dorsal forebrain, do not show this ectopic phenotype and partially restore brain size after irradiation. Irradiation furthermore induces an epithelial-to-mesenchymal transition-like process resembling the radiation-induced proneural-mesenchymal transition in glioma and glioma stem-like cells. Our results demonstrate a critical role for p53 beyond the DDR as a regulator of neural progenitor cell fate in response to DNA damage.

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“…Rab13 upstream regulators remain poorly characterized; however, a growing body of evidence indicates that Rab13 expression during neurite outgrowth and axon regeneration is driven by the transcription factor p53 [Di Giovanni et al, 2005Giovanni et al, , 2006Eom et al, 2015;Ma et al, 2011]. Rab13 GEFs and GAPs involved in this process are still unknown.…”

Section: Rab13mentioning

confidence: 99%

Rab GTPase signaling in neurite outgrowth and axon specification

2016

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Neurons are highly polarized cells that contain specialized subcellular domains involved in information transmission in the nervous system. Specifically, the somatodendritic compartment receives neuronal inputs while the axons convey information through the synapse. The establishment of asymmetric domains requires a specific delivery of components, including organelles, proteins, and membrane. The Rab family of small GTPases plays an essential role in membrane trafficking. Signaling cascades triggered by extrinsic and intrinsic factors tightly regulate Rab functions in cells, with Rab protein activation depending on GDP/GTP binding to establish a binary mode of action. This review summarizes the contributions of several Rab family members involved in trans-Golgi, early/late endosomes, and recycling endosomes during neurite development and axonal outgrowth. The regulation of some Rabs by guanine exchanging factors and GTPase activating proteins will also be addressed. Finally, discussion will be provided on how specific effector-mediated Rab activation modifies several molecules essential to neuronal differentiation. V C 2016 Wiley Periodicals, Inc.

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Ionizing radiation induces neuronal differentiation of Neuro-2a cells via PI3-kinase and p53-dependent pathways

Cited by 16 publications

References 54 publications

SOCS3 induces neurite differentiation and promotes neuronal cell survival

SOCS3 induces neurite differentiation and promotes neuronal cell survival

p53 drives premature neuronal differentiation in response to radiation-induced DNA damage during early neurogenesis

Rab GTPase signaling in neurite outgrowth and axon specification

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