Sonic hedgehog promotes neurite outgrowth of cortical neurons under oxidative stress: Involving of mitochondria and energy metabolism

He, Weiliang; Cui, Lili; Zhang, Cong; Zhang, Xiangjian; He, Jianbin; Xie, Yanzhao; Chen, Yanxia

doi:10.1016/j.yexcr.2016.11.008

Cited by 27 publications

(25 citation statements)

References 59 publications

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“…Enzyme linked immunosorbent assay kits were used to measure the mouse serum concentrations of tumor necrosis factor-α (TNF-α) (29-8321-65, Thermo Fisher Scientific, MA, United States), interleukin-1β (IL-1β) (29-8012-65, Thermo Fisher Scientific, MA, United States), IL-6 (29-8061-65, Thermo Fisher Scientific, MA, United States), superoxide dismutase (SOD) (DYC3419-2, R&D Systems, Minneapolis, MN, United States), malondialdehyde (MDA) (69-21068, Wuhan Msk Biotechnology Co., Ltd., Wuhan, China), glutathione (GSH) (69-80233, Wuhan Msk Biotechnology Co., Ltd., Wuhan, China) and catalase (CAT) (69-210385, Wuhan Msk Biotechnology Co., Ltd., Wuhan, China) (He et al, 2017). Experiments were conducted according to manufacturer's instructions.…”

Section: Enzyme Linked Immunosorbent Assay (Elisa)mentioning

confidence: 99%

Geniposide Alleviates Oxidative Stress of Mice With Depression-Like Behaviors by Upregulating Six3os1

Zou

Sugimoto

Zhang

et al. 2020

Front. Cell Dev. Biol.

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Depression is a major cause of disease burden and severely impairs well-being of patients around the globe. Geniposide (GP) has been revealed to play a significant role in depression treatment. Of note, RNA sequencing of this study identified highly expressed long non-coding RNA Six3os1 in response to GP treatment. Thus, we aim to explore how GP affected chronic unpredictable mild stress (CUMS)-induced depressionlike behaviors in mice in vivo and in vitro and the downstream molecular mechanism related to Six3os1. The relationship of Six3os1, miR-511-3p and Fezf1 was evaluated by dual-luciferase reporter gene assay, RIP assay, and RNA pulling down assay. Ectopic expression and knockdown experiments were developed in CUMS-induced mice and neurons with or without GP treatment. In vitro experiments and behavioral tests were conducted to examine alteration of CUMS-triggered oxidative stress following different interferences. The experimental data validated that GP treatment resulted in high expression of Six3os1 and Fezf1 and poor expression of miR-511-3p in CUMS-induced neurons. Six3os1 activated the AKT signaling pathway by upregulating miR-511-3ptargeted Fezf1. Either GP treatment or overexpression of Six3os1 or Fezf1 alleviated depression-like behaviors of CUMS-induced mice. GP treatment, miR-511-3p inhibition or overexpression of Six3os1 or Fezf1 not only reduced oxidative stress in CUMSinduced mice and neurons, but also reduced CUMS-induced neuronal apoptosis. Collectively, GP treatment-mediated Six3os1 upregulation ameliorated oxidative stress of mice with depression-like behaviors via the miR-511-3p/Fezf1/AKT axis.

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Section: Enzyme Linked Immunosorbent Assay (Elisa)mentioning

confidence: 99%

Geniposide Alleviates Oxidative Stress of Mice With Depression-Like Behaviors by Upregulating Six3os1

Zou

Sugimoto

Zhang

et al. 2020

Front. Cell Dev. Biol.

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“…In a similar in vitro model, it was demonstrated that Shh, acting as a prosurvival factor, plays a crucial part in neurite outgrowth in the H 2 O 2 -treated cortical neurons. Potential mechanisms underlying the antioxidative efficacies of Shh may include counteracting ROS release, prevention of mitochondrial dysfunction, promotion of ATP production, as well as preservation of mitochondrial complex II activities against oxidative stress [119]. …”

Section: Sonic Hedgehog and Antioxidation In Neurological Diseasesmentioning

confidence: 99%

Emerging Roles of Sonic Hedgehog in Adult Neurological Diseases: Neurogenesis and Beyond

Chen

Yang

Hwang

et al. 2018

IJMS

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Sonic hedgehog (Shh), a member of the hedgehog (Hh) family, was originally recognized as a morphogen possessing critical characters for neural development during embryogenesis. Recently, however, Shh has emerged as an important modulator in adult neural tissues through different mechanisms such as neurogenesis, anti-oxidation, anti-inflammation, and autophagy. Therefore, Shh may potentially have clinical application in neurodegenerative diseases and brain injuries. In this article, we present some examples, including ours, to show different aspects of Shh signaling and how Shh agonists or mimetics are used to alter the neuronal fates in various disease models, both in vitro and in vivo. Other potential mechanisms that are discussed include alteration of mitochondrial function and anti-aging effect; both are critical for age-related neurodegenerative diseases. A thorough understanding of the protective mechanisms elicited by Shh may provide a rationale to design innovative therapeutic regimens for various neurodegenerative diseases.

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“…One study demonstrated increased abundance of Notch proteins in spinal cords from SOD1 G93A transgenic mice and NSC34 cells transfected with mutant SOD1 [ 74 ]. However, hedgehog activation is cytoprotective against oxidative stress [ 75 – 77 ], and hedgehog activity is repressed in CSF from ALS patients [ 78 ]. While GM6 may activate Notch and hedgehog independently, we favor a model involving Notch-hedgehog crosstalk, in which GM6 up-regulates Notch ligand and receptors with secondary activation of hedgehog.…”

Section: Discussionmentioning

confidence: 99%

GM604 regulates developmental neurogenesis pathways and the expression of genes associated with amyotrophic lateral sclerosis

Bojanowski

Kindy

Chau³

et al. 2018

Transl Neurodegener

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BackgroundAmyotrophic lateral sclerosis (ALS) is currently an incurable disease without highly effective pharmacological treatments. The peptide drug GM604 (GM6 or Alirinetide) was developed as a candidate ALS therapy, which has demonstrated safety and good drug-like properties with a favorable pharmacokinetic profile. GM6 is hypothesized to bolster neuron survival through the multi-target regulation of developmental pathways, but mechanisms of action are not fully understood.MethodsThis study used RNA-seq to evaluate transcriptome responses in SH-SY5Y neuroblastoma cells following GM6 treatment (6, 24 and 48 h).ResultsWe identified 2867 protein-coding genes with expression significantly altered by GM6 (FDR < 0.10). Early (6 h) responses included up-regulation of Notch and hedgehog signaling components, with increased expression of developmental genes mediating neurogenesis and axon growth. Prolonged GM6 treatment (24 and 48 h) altered the expression of genes contributing to cell adhesion and the extracellular matrix. GM6 further down-regulated the expression of genes associated with mitochondria, inflammatory responses, mRNA processing and chromatin organization. GM6-increased genes were located near GC-rich motifs interacting with C2H2 zinc finger transcription factors, whereas GM6-decreased genes were located near AT-rich motifs associated with helix-turn-helix homeodomain factors. Such motifs interacted with a diverse network of transcription factors encoded by GM6-regulated genes (STAT3, HOXD11, HES7, GLI1). We identified 77 ALS-associated genes with expression significantly altered by GM6 treatment (FDR < 0.10), which were known to function in neurogenesis, axon guidance and the intrinsic apoptosis pathway.ConclusionsOur findings support the hypothesis that GM6 acts through developmental-stage pathways to influence neuron survival. Gene expression responses were consistent with neurotrophic effects, ECM modulation, and activation of the Notch and hedgehog neurodevelopmental pathways. This multifaceted mechanism of action is unique among existing ALS drug candidates and may be applicable to multiple neurodegenerative diseases.Electronic supplementary materialThe online version of this article (10.1186/s40035-018-0135-7) contains supplementary material, which is available to authorized users.

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Sonic hedgehog promotes neurite outgrowth of cortical neurons under oxidative stress: Involving of mitochondria and energy metabolism

Cited by 27 publications

References 59 publications

Geniposide Alleviates Oxidative Stress of Mice With Depression-Like Behaviors by Upregulating Six3os1

Geniposide Alleviates Oxidative Stress of Mice With Depression-Like Behaviors by Upregulating Six3os1

Emerging Roles of Sonic Hedgehog in Adult Neurological Diseases: Neurogenesis and Beyond

GM604 regulates developmental neurogenesis pathways and the expression of genes associated with amyotrophic lateral sclerosis

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