Indirubin-3-Oxime Prevents H2O2-Induced Neuronal Apoptosis via Concurrently Inhibiting GSK3β and the ERK Pathway

Li, Jingling; Zheng, Jin; Lin, Jiajia; jin, L v Hai; Yu, Rui; Mak, Shinghung; Hu, Songhua; Sun, Hongya; Wu, Xiang; Zhang, Zaijun; Lee, Simon Ming‐Yuen; Wah-keung, Tsim; Su, Wei; Zhou, Wenhua; Cui, Wei; Han, Yifan; Wang, Qinwen

doi:10.1007/s10571-016-0402-z

Cited by 21 publications

(17 citation statements)

References 36 publications

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“…FDA/PI double staining was performed according to our previous publication [ 17 ]. Viable cells were visualized by the fluorescein formed from FDA by esterase activity in the cytoplasm.…”

Section: Methodsmentioning

confidence: 99%

Fucoxanthin, a Marine Carotenoid, Attenuates β-Amyloid Oligomer-Induced Neurotoxicity Possibly via Regulating the PI3K/Akt and the ERK Pathways in SH-SY5Y Cells

Lin

Zhao

et al. 2017

Oxidative Medicine and Cellular Longevity

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Alzheimer's disease (AD), the most common neurodegenerative disorder, is characterized by neurofibrillary tangles, synaptic impairments, and loss of neurons. Oligomers of β-amyloid (Aβ) are widely accepted as the main neurotoxins to induce oxidative stress and neuronal loss in AD. In this study, we discovered that fucoxanthin, a marine carotenoid with antioxidative stress properties, concentration dependently prevented Aβ oligomer-induced increase of neuronal apoptosis and intracellular reactive oxygen species in SH-SY5Y cells. Aβ oligomers inhibited the prosurvival phosphoinositide 3-kinase (PI3K)/Akt cascade and activated the proapoptotic extracellular signal-regulated kinase (ERK) pathway. Moreover, inhibitors of glycogen synthase kinase 3β (GSK3β) and mitogen-activated protein kinase (MEK) synergistically prevented Aβ oligomer-induced neuronal death, suggesting that the PI3K/Akt and ERK pathways might be involved in Aβ oligomer-induced neurotoxicity. Pretreatment with fucoxanthin significantly prevented Aβ oligomer-induced alteration of the PI3K/Akt and ERK pathways. Furthermore, LY294002 and wortmannin, two PI3K inhibitors, abolished the neuroprotective effects of fucoxanthin against Aβ oligomer-induced neurotoxicity. These results suggested that fucoxanthin might prevent Aβ oligomer-induced neuronal loss and oxidative stress via the activation of the PI3K/Akt cascade as well as inhibition of the ERK pathway, indicating that further studies of fucoxanthin and related compounds might lead to a useful treatment of AD.

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“…FDA/PI double staining was performed according to our previous publication [ 17 ]. Viable cells were visualized by the fluorescein formed from FDA by esterase activity in the cytoplasm.…”

Section: Methodsmentioning

confidence: 99%

Fucoxanthin, a Marine Carotenoid, Attenuates β-Amyloid Oligomer-Induced Neurotoxicity Possibly via Regulating the PI3K/Akt and the ERK Pathways in SH-SY5Y Cells

Lin

Zhao

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…A study of the molecular structure of indirubin indicates that it has a more three-dimensional structure compared to the more planar structure of the indigo molecule which is another component of indigo naturalis [ 53 ]. Indirubin is also a potent cyclin-dependent kinase inhibitor which is neuroprotective, attenuates high fat-high fructose induced Aβ-aggregation, and prevents tau-phosphorylation in Alzheimer’s disease animal models [ 54 , 55 , 56 , 57 , 58 , 59 , 60 ].…”

Section: Discussionmentioning

confidence: 99%

Functions of Small Organic Compounds that Mimic the HNK-1 Glycan

Wang

Theis

Kabat

et al. 2020

IJMS

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Because of the importance of the HNK-1 carbohydrate for preferential motor reinnervation after injury of the femoral nerve in mammals, we screened NIH Clinical Collection 1 and 2 Libraries and a Natural Product library comprising small organic compounds for identification of pharmacologically useful reagents. The reason for this attempt was to obviate the difficult chemical synthesis of the HNK-1 carbohydrate and its isolation from natural sources, with the hope to render such compounds clinically useful. We identified six compounds that enhanced neurite outgrowth from cultured spinal motor neurons at nM concentrations and increased their neurite diameter, but not their neurite branch points. Axons of dorsal root ganglion neurons did not respond to these compounds, a feature that is in agreement with their biological role after injury. We refer to the positive functions of some of these compounds in animal models of injury and delineate the intracellular signaling responses elicited by application of compounds to cultured murine central nervous system neurons. Altogether, these results point to the potential of the HNK-1 carbohydrate mimetics in clinically-oriented settings.

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“…The authors of that study proposed that the direct binding of indirubin 3-oxime to YB-1 leads to disruption of the YB-1 interaction with transportin 1 that mediates its transport through a nucleus pore [61]. However, indirubin 3-oxime is also known to inhibit the activity of several kinases, including Akt [62]. Hence, indirubin 3-oxime possibly interferes with YB-1 phosphorylation, thereby affecting the YB-1 translocation to the nucleus.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Transcription Induces Phosphorylation of YB-1 at Ser102 and Its Accumulation in the Nucleus

Kretov

Mordovkina

Eliseeva

et al. 2019

Cells

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The Y-box binding protein 1 (YB-1) is an RNA/DNA-binding protein regulating gene expression in the cytoplasm and the nucleus. Although mostly cytoplasmic, YB-1 accumulates in the nucleus under stress conditions. Its nuclear localization is associated with aggressiveness and multidrug resistance of cancer cells, which makes the understanding of the regulatory mechanisms of YB-1 subcellular distribution essential. Here, we report that inhibition of RNA polymerase II (RNAPII) activity results in the nuclear accumulation of YB-1 accompanied by its phosphorylation at Ser102. The inhibition of kinase activity reduces YB-1 phosphorylation and its accumulation in the nucleus. The presence of RNA in the nucleus is shown to be required for the nuclear retention of YB-1. Thus, the subcellular localization of YB-1 depends on its post-translational modifications (PTMs) and intracellular RNA distribution.

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Indirubin-3-Oxime Prevents H2O2-Induced Neuronal Apoptosis via Concurrently Inhibiting GSK3β and the ERK Pathway

Cited by 21 publications

References 36 publications

Fucoxanthin, a Marine Carotenoid, Attenuates β-Amyloid Oligomer-Induced Neurotoxicity Possibly via Regulating the PI3K/Akt and the ERK Pathways in SH-SY5Y Cells

Fucoxanthin, a Marine Carotenoid, Attenuates β-Amyloid Oligomer-Induced Neurotoxicity Possibly via Regulating the PI3K/Akt and the ERK Pathways in SH-SY5Y Cells

Functions of Small Organic Compounds that Mimic the HNK-1 Glycan

Inhibition of Transcription Induces Phosphorylation of YB-1 at Ser102 and Its Accumulation in the Nucleus

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