Lactate promotes neuronal differentiation of SH-SY5Y cells by lactate-responsive gene sets through NDRG3-dependent and -independent manners

Xu, Yidan; Kusuyama, Joji; Osana, Shion; Matsuhashi, Sachiko; Li, Longfei; Takada, H.; Inada, Hitoshi; Nagatomi, Ryoichi

doi:10.1016/j.jbc.2023.104802

Cited by 8 publications

(2 citation statements)

References 142 publications

(172 reference statements)

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“…However, when comparing the effect of the two doses tested we have also identified proteins showing opposite regulation ( Supplementary Figure 1 ) that might explain potential adverse effects of the use of high doses. Among those showing similar regulation ( Table 1 ), we have found key proteins involved in the regulation of neuronal differentiation (Ndrg3), neuronal survival (Dynlrb1), antioxidant activity important for neuron survival (Lancl1), cognitive function (Tsnax), as well as hippocampal neurons development and spatial memory (Rab35) (Huang et al, 2014 , 2023 ; Terenzio et al, 2020 ; Maejima et al, 2023 ; Xu et al, 2023 ). All these proteins were up-regulated by both fasudil doses tested and might suggest consistent beneficial proteome regulations in PS19 mice.…”

Section: Discussionmentioning

confidence: 91%

Effect of the ROCK inhibitor fasudil on the brain proteomic profile in the tau transgenic mouse model of Alzheimer's disease

Collu,

Yin,

Giunti

et al. 2024

Front. Aging Neurosci.

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IntroductionThe goal of this study is to explore the pharmacological potential of the amyloid-reducing vasodilator fasudil, a selective Ras homolog (Rho)-associated kinases (ROCK) inhibitor, in the P301S tau transgenic mouse model (Line PS19) of neurodegenerative tauopathy and Alzheimer's disease (AD).MethodsWe used LC-MS/MS, ELISA and bioinformatic approaches to investigate the effect of treatment with fasudil on the brain proteomic profile in PS19 tau transgenic mice. We also explored the efficacy of fasudil in reducing tau phosphorylation, and the potential beneficial and/or toxic effects of its administration in mice.ResultsProteomic profiling of mice brains exposed to fasudil revealed the activation of the mitochondrial tricarboxylic acid (TCA) cycle and blood-brain barrier (BBB) gap junction metabolic pathways. We also observed a significant negative correlation between the brain levels of phosphorylated tau (pTau) at residue 396 and both fasudil and its metabolite hydroxyfasudil.ConclusionsOur results provide evidence on the activation of proteins and pathways related to mitochondria and BBB functions by fasudil treatment and support its further development and therapeutic potential for AD.

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Section: Discussionmentioning

confidence: 91%

Effect of the ROCK inhibitor fasudil on the brain proteomic profile in the tau transgenic mouse model of Alzheimer's disease

Collu,

Yin,

Giunti

et al. 2024

Front. Aging Neurosci.

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“…Other findings seem to contradict our hypothesis that RA would reduce stemness features and promote differentiation in SK-ES-1 cells. In both SH-SY5Y NB [49] and ES [50] cells, neural differentiation with neurite outgrowth is accompanied by increased expression of TUBB3, which is widely used as a marker of neural differentiation. On the other hand, a drug-induced loss of viability in ES cells can be associated with a reduction in TUBB3 expression [51], thus the reduced expression of TUBB3 we observed might be associated with the antitumor effect of RA in reducing cell viability.…”

Section: Discussionmentioning

confidence: 99%

Stemness and Cell Cycle Regulators and Their Modulation by Retinoic Acid in Ewing Sarcoma

Battistella,

Freire,

Toson

et al. 2024

CIMB

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Retinoic acid (RA) regulates stemness and differentiation in human embryonic stem cells (ESCs). Ewing sarcoma (ES) is a pediatric tumor that may arise from the abnormal development of ESCs. Here we show that RA impairs the viability of SK-ES-1 ES cells and affects the cell cycle. Cells treated with RA showed increased levels of p21 and its encoding gene, CDKN1A. RA reduced mRNA and protein levels of SRY-box transcription factor 2 (SOX2) as well as mRNA levels of beta III Tubulin (TUBB3), whereas the levels of CD99 increased. Exposure to RA reduced the capability of SK-ES-1 to form tumorspheres with high expression of SOX2 and Nestin. Gene expression of CD99 and CDKN1A was reduced in ES tumors compared to non-tumoral tissue, whereas transcript levels of SOX2 were significantly higher in tumors. For NES and TUBB3, differences between tumors and control tissue did not reach statistical significance. Low expression of CD99 and NES, and high expression of SOX2, were significantly associated with a poorer patient prognosis indicated by shorter overall survival (OS). Our results indicate that RA may display rather complex modulatory effects on multiple target genes associated with the maintenance of stem cell’s features versus their differentiation, cell cycle regulation, and patient prognosis in ES.

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Lifestyle Factors Affecting Biological Processes and Health

Anisman,

Hayley,

Kusnecov

2025

The Immune System

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Lactate promotes neuronal differentiation of SH-SY5Y cells by lactate-responsive gene sets through NDRG3-dependent and -independent manners

Cited by 8 publications

References 142 publications

Effect of the ROCK inhibitor fasudil on the brain proteomic profile in the tau transgenic mouse model of Alzheimer's disease

Effect of the ROCK inhibitor fasudil on the brain proteomic profile in the tau transgenic mouse model of Alzheimer's disease

Stemness and Cell Cycle Regulators and Their Modulation by Retinoic Acid in Ewing Sarcoma

Lifestyle Factors Affecting Biological Processes and Health

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