Influence of N-Arachidonoyl Dopamine and N-Docosahexaenoyl Dopamine on the Expression of Neurotrophic Factors in Neuronal Differentiated Cultures of Human Induced Pluripotent Stem Cells under Conditions of Oxidative Stress.

Ekaterina Novosadova,Igor Grivennikov,Vladimir Bezuglov,Anna Vetchinova,Ludmila Novosadova,Stanislav Antonov,Sergey Illarioshkin,Ludmila Inozemtseva,Oleg Dolotov,Darya Shimchenko,Vyacheslav Tarantul

doi:10.3390/antiox11010142

Ekaterina Novosadova, Igor Grivennikov + Show 9 more

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https://doi.org/10.3390/antiox11010142

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Abstract

Oxidative stress (OS) is implicated in the pathogenesis of several neurodegenerative diseases. We have previously shown that N-acyl dopamines (N-ADA and N-DDA) protect the neural cells of healthy donors and patients with Parkinson’s disease from OS. In this study, we assessed the effects of N-acyl dopamines on the expression of neurotrophic factors in human-induced pluripotent stem cell-derived neuronal cultures enriched with dopaminergic neurons under conditions of OS induced by hydrogen peroxide. We showed that hydrogen peroxide treatment increased BDNF but not GDNF mRNA levels, while it did not affect the secretion of corresponding proteins into the culture medium of these cells. Application of N-acyl dopamines promoted BDNF release into the culture medium. Under conditions of OS, N-DDA also increased TRKB, TRKC and RET mRNA levels. Furthermore, N-acyl dopamines prevented cell death 24 h after OS induction and promoted the expression of antioxidant enzymes GPX1, GPX7, SOD1, SOD2 and CAT, as well as reduced the BAX/BCL2 mRNA ratio. These findings indicate that stimulation of the expression of neurotrophic factors and their receptors may underlie the neuroprotective effects of N-acyl dopamines in human neurons.

Highlights

We have shown that N-arachidonoyl dopamine (N-ADA) and N-docosahexaenoyl dopamine (N-DDA) exert neuroprotective effects in the cultures of neuronal progenitors differentiated from human induced pluripotent stem cells obtained from a healthy donor in the model of oxidative stress (OS) induced by hydrogen peroxide [10]
In this work, we investigated the effects of N-ADA and N-DDA on the expression of some key genes of neurotrophic factors (NTFs), such as BDNF, glial cell derived neurotrophic factor (GDNF), NGF, NT3 and their receptors, in the model of OS induced by hydrogen peroxide (H2 O2 ) in differentiated cultures of neurons derived from human induced pluripotent stem cells (iPSC)
We used human iPSC-derived differentiated neuronal cell cultures enriched by DA neurons. iPSC line of healthy donor was generated by our team previously in the Laboratory of Molecular Genetics of Somatic Cells, Institute of Molecular Genetics of Russian Academy of Sciences (Moscow, Russia)

Summary

Introduction

Licensee MDPI, Basel, Switzerland.Attribution (CC BY) license (https://creativecommons.org/licenses/by/ 4.0/).N-acyldophamines are endogenous conjugates of dopamine and long-chain fatty acids.N-docosahexaenoyl dopamine (N-DDA) and N-arachidonoyl dopamine (N-ADA), as well as some other N-acyldopamines, exhibited potency to activate cannabinoid receptor-1(CB1) and vanilloid TRPV-1 receptor [1,2] and thus can be attributed to the large family of cannabinoid-like/endovanilloid compounds [3].These compounds have previously been shown to have antioxidant and neuroprotective properties in various models of oxidative stress (OS) in vitro and in vivo. Bobrov et al.

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