Netrin-1 Prevents Rat Primary Cortical Neurons from Apoptosis via the DCC/ERK Pathway

Chen, Jianhao; Du, Houwei; Zhang, Yixian; Chen, Hongbin; Zheng, Mouwei; Lin, Peiqiang; Lan, Quan; Yuan, Qilin; Lai, Yongxing; Pan, Xiaodong; Chen, Ronghua; Liu, Nan

doi:10.3389/fncel.2017.00387

Cited by 25 publications

(15 citation statements)

References 41 publications

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“…Here, we found that netrin-1 ameliorated UV-Binduced mitochondrial dysfunction and LDH release. Indeed, netrin-1 treatment has been shown to attenuate cell death and neuronal apoptosis in cultured primary cortical neurons after oxygen-glucose-deprivation (OGD) injury [24]. It should be noticed that UV-B exposure debilitated the features of ESCs through reducing the expression of integrin b1 and Krt19, two important ESC markers.…”

Section: Discussionmentioning

confidence: 99%

Netrin-1 plays a critical role in regulating capacities of epidermal stem cells upon ultraviolet-B (UV-B) irradiation

Cao

Zhao

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Loss of the capacities of epidermal stem cells (ESCs) induced by ultraviolet-B (UV-B) irradiation has been widely associated with various skin diseases. Netrin-1, a member of the axonal guidance protein family, has displayed diverse biological functions in different types of cells and tissues, mediated by its specific receptor UNC-5 homolog B (UNC5b). In this study, we examined the physiological functions of netrin-1 and UNC5b in ESCs upon UV-B exposure. Our results indicate that UNC5b is expressed in ESCs, and its expression is upregulated in response to UV-B radiation. We found that treatment with netrin-1 prevented UV-B radiation-induced oxidative stress by reducing the generation of reactive oxygen species (ROS) and expression of NADPH oxidase 4 (NOX-4). Additionally, treatment with netrin-1 improved UV-B radiation-induced mitochondrial dysfunction by increasing mitochondrial membrane potential (MMP) levels and adenosine triphosphate (ATP) production. The presence of netrin-1 attenuated UV-B radiation-induced lactic dehydrogenase (LDH) release. UV-B exposure resulted in the loss of the capacities of ESCs by reducing the expressions of integrin b1 and Krt19, the two major ESC markers. Importantly, this process was prevented by netrin-1. Silencing of UNC5b abolished the effects of netrin-1 on the expression of integrin b1 and Krt19, suggesting that the effects of netrin-1 in maintaining the capacities of ESCs are dependent on UNC5b. Mechanistically, we found that the Wnt/b-catenin signalling may be involved. Our findings suggest that netrin-1 may serve as a therapeutic agent for the treatment of skin diseases. ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 99%

Netrin-1 plays a critical role in regulating capacities of epidermal stem cells upon ultraviolet-B (UV-B) irradiation

Cao

Zhao

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…For example, NT-1 interacted with DCC and activated the ERK pathway to promote the proliferation of endothelial cells and angiogenesis [ 31 ]. NT-1 combined with DCC to reduce the DNA damage and apoptosis in cultured primary neurons [ 32 ]. UNC5H2 was the receptor responsible for protecting BBB breakdown [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Netrin-1 attenuates brain injury after middle cerebral artery occlusion via downregulation of astrocyte activation in mice

Liu

Lin

et al. 2018

J Neuroinflammation

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BackgroundNetrin-1 functions largely via combined receptors and downstream effectors. Evidence has shown that astrocytes express netrin-1 receptors, including DCC and UNC5H2. However, whether netrin-1 influences the function of astrocytes was previously unknown.MethodsLipopolysaccharide was used to stimulate the primary cultured astrocytes; interleukin release was used to track astrocyte activation. In vivo, shRNA and netrin-1 protein were injected in the mouse brain. Infarct volume, astrocyte activation, and interleukin release were used to observe the function of netrin-1 in neuroinflammation and brain injury after middle cerebral artery occlusion.ResultsOur results demonstrated that netrin-1 reduced lipopolysaccharide-induced interleukin-1β and interleukin-12β release in cultured astrocytes, and blockade of the UNC5H2 receptor with an antibody reversed this effect. Additionally, netrin-1 increased p-AKT and PPAR-γ expression in primary cultured astrocytes. In vivo studies showed that knockdown of netrin-1 increased astrocyte activation in the mouse brain after middle cerebral artery occlusion (p < 0.05). Moreover, injection of netrin-1 attenuated GFAP expression (netrin-1 0.27 ± 0.06 vs. BSA 0.62 ± 0.04, p < 0.001) and the release of interleukins and reduced infarct volume after brain ischemia (netrin-1 0.27 ± 0.06 vs. BSA 0.62 ± 0.04 mm3, p < 0.05).ConclusionOur results indicate that netrin-1 is an important molecule in regulating astrocyte activation and neuroinflammation in cerebral ischemia and provides a potential target for ischemic stroke therapy.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1291-5) contains supplementary material, which is available to authorized users.

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“…For example, in some postmitotic cells, such as neurons, IGF‐1 protects them from apoptosis by upregulating the antiapoptotic protein Bcl‐2 and decreasing caspase‐3 activity . In addition, netrin‐1 protects cortical neurons from apoptosis by activating the ERK signaling pathway . In this context, we suggest that in response to certain cell damage, insulin/IGF‐1 inhibits apoptosis to control tissue destruction and contributes to cell survival, proliferation, damage repair, and regeneration.…”

Section: Mechanisms Of Apoptosis Dysregulation In Agingmentioning

confidence: 93%

Advantages and disadvantages of apoptosis in the aging process

Argüelles

Guerrero‐Castilla

Cano

et al. 2019

Annals of the New York Academy of Sciences

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Researchers cannot predict as yet how long a human being can live. Life expectancy has been steadily increasing in the last century, but perhaps not always the quality of life in parallel with it. Future generations will be faced with the problems of an increased life expectancy along with the emergence of new age-related diseases. A deeper understanding of the aging process is crucial to ameliorate, if not to prevent, these projected new old-age diseases. One of the mechanisms responsible for healthy aging is through the effective maintenance of physiological, biochemical, and immunological functions. To carry this out, the organism needs to create new cells to replace old ones and to induce the disappearance of old and damaged cells. Apoptosis is involved in all these processes. However, if apoptosis is dysregulated, premature senescence-associated diseases are likely to appear. In our review, the focus will be on a better understanding of the role of apoptosis in the aging process. These signaling pathways will most assuredly be pharmacologically targeted in antiaging medicine therapies.

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Netrin-1 Prevents Rat Primary Cortical Neurons from Apoptosis via the DCC/ERK Pathway

Cited by 25 publications

References 41 publications

Netrin-1 plays a critical role in regulating capacities of epidermal stem cells upon ultraviolet-B (UV-B) irradiation

Netrin-1 plays a critical role in regulating capacities of epidermal stem cells upon ultraviolet-B (UV-B) irradiation

Netrin-1 attenuates brain injury after middle cerebral artery occlusion via downregulation of astrocyte activation in mice

Advantages and disadvantages of apoptosis in the aging process

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