RA Differentiation Enhances Dopaminergic Features, Changes Redox Parameters, and Increases Dopamine Transporter Dependency in 6-Hydroxydopamine-Induced Neurotoxicity in SH-SY5Y Cells

Lopes, Fernanda Machado; Motta, Leonardo Lisbôa da; Bastiani, Marco Antônio De; Pfaffenseller, Bianca; Aguiar, Bianca Wollenhaupt de; Souza, Luiz Felipe de; Zanatta, Geancarlo; Vargas, Daiani Machado de; Schönhofen, Patrícia; Londero, Giovana Ferreira; Medeiros, Liana Marengo de; Freire, V. N.; Dafre, Alcir Luiz; Castro, Mauro A. A.; Parsons, Richard B.; Klamt, Fábio

doi:10.1007/s12640-016-9699-0

Cited by 38 publications

(41 citation statements)

References 63 publications

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“…Previous studies showed that 4-11 days of RA treatment increase the number of catecholaminergic neurons in the SH-SY5Y cells [42]. Accordingly, we found that after a 5-day RA treatment, SH-SY5Y cells efficiently accumulated [ 3 H]DA and, while the NET specific inhibitor desipramine [43] completely blocked DA uptake, the GBR12935 blocker, which has a higher affinity to DAT than NET [44], only partially diminished DA uptake.…”

Section: Discussionsupporting

confidence: 55%

“…when the SH-SY5Y cells exhibit features typical of an early neuronal differentiation stage or neural progenitor cells [36][37][38][39], but DAT/NET function was measured after RA-induced differentiation, i.e. when SH-SY5Y cells exhibit both morphological and biochemical features similar to those observed in differentiated neurons [29,[40][41][42]. Thus, we speculate that prolonged AMPH exposures during proliferation and differentiation of primordial neuronal cells change DA reuptake in mature neurons.…”

Section: Discussionmentioning

confidence: 99%

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Prolonged Amphetamine Treatments Cause Long-Term Decrease of Dopamine Uptake in Cultured Cells

et al. 2019

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Amphetamine (AMPH) is a systemic stimulant used to treat a variety of diseases including Attention Deficit Hyperactive Disorder, narcolepsy and obesity. Previous data showed that by binding to catecholamine transporters, AMPH prevents the reuptake of the neurotransmitters dopamine (DA) and norepinephrine (NE). Because AMPH, either used therapeutically at final concentrations of 1-10 µM or abused as recreational drug (50-200 µM), is taken over long periods of time, we investigated the prolonged effects of this drug on the uptake of DA. We found that, in LLC-PK1 cells stably expressing the human DA transporter (hDAT), pretreatments with 1 or 50 µM AMPH caused significant reduction in DA uptake right after the 15-h pretreatment. Remarkably, after 50 but not 1 µM AMPH pretreatment, we observed a significant reduction in DA uptake also after one, two or three cell divisions. To test whether these long-term effects induced by AMPH where conserved in a model comparable to primordial neuronal cells and native neurons, we used the human neuroblastoma cell line SH-SY5Y cells, which were reported to endogenously express both hDAT and the NE transporter. Pretreatments with 50 µM AMPH caused a significant reduction of DA uptake both right after 15 h and 3 cell divisions followed by neuro-differentiation with retinoic acid (RA) for 5 days. Under these same conditions, AMPH did not change the intracellular concentrations of ATP, ROS and cell viability suggesting, therefore, that the reduction in DA uptake was not cause by AMPH-induced toxicity. Interestingly, while 1 µM AMPH did not cause long-term effects in the LLC-PK1 cells, in the SH-SY5Y cells, it decreased the DA uptake after one, two, but not three, cell divisions and 5-day RA differentiation. These data show that besides the well-known acute effects, AMPH can also produce long-term effects in vitro that are maintained during cell division and transmitted to the daughter cells.

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Prolonged Amphetamine Treatments Cause Long-Term Decrease of Dopamine Uptake in Cultured Cells

et al. 2019

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“…It is possible that α-Syn as a synaptic protein [8] requires a certain differentiated state with neuronal processes which are not present in undifferentiated neuroblastoma cells which are cancer cells . Morphological similarities between human neurons and differentiated neuroblastoma cells have been described recently together with a marked increase in gene expression of synaptic components and dopamine processes in differentiated cells [19].…”

Section: Discussionmentioning

confidence: 87%

Characterisation of Oxidative Stress, DNA Damage and Inflammation in a Cellular Model of Parkinson’s Disease

Khan¹,

Wan²,

Hunter³

et al. 2019

obm neurobiol

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Background: Parkinson's disease (PD) is the second most common neurodegenerative disease and is a synucleinopathy due to the critical role of α-synuclein (α-Syn) in its pathology. α-Syn is able to translocate from the cytoplasm to the nucleus and cause DNA damage. Methods: SH-SY5Y cells were stably transfected with plasmids containing wild type (WT) α-Syn and A53T mutant α-Syn as fusion proteins with EGFP and an EGFP only control vector. The cells were differentiated using retinoid acid (RA) and treated with hydrogen peroxide (H 2 O 2) and analysed in a differentiated state for the effects of oxidative stress using flow cytometry, DNA damage using γH2A.X staining and inflammatory and senescence markers using qPCR.

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“…In the present study, in an in vitro model of PD, C. aurantium could majorly maintain cell viability and downregulate apoptotic signals, based on the analysis of ethanolic extracts; hence, C. aurantium could exhibit protective and neurorestorative characteristics. Nevertheless, this question remains as to how the extracts apply their protective effects at cellular or molecular level (Schwanz et al, 1996) .…”

Section: Discussionmentioning

confidence: 99%

“…In general, SH-SY5Y cell line expresses dopamine beta-hydroxylase, tyrosine hydroxylase, and dopamine transporters (Lopes et al, 2017). Consequently, it is applied in in vitro models of PD; moreover, it helps examine the protective effects of different drugs.…”

Section: Introductionmentioning

confidence: 99%

The Protective Effects of Citrus aurantium Flower Extract against 6-Hydroxydopamine-Mediated Cell Damage in Human Neuroblastoma SH-SY5Y Cells

et al. 2018

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RA Differentiation Enhances Dopaminergic Features, Changes Redox Parameters, and Increases Dopamine Transporter Dependency in 6-Hydroxydopamine-Induced Neurotoxicity in SH-SY5Y Cells

Cited by 38 publications

References 63 publications

Prolonged Amphetamine Treatments Cause Long-Term Decrease of Dopamine Uptake in Cultured Cells

Prolonged Amphetamine Treatments Cause Long-Term Decrease of Dopamine Uptake in Cultured Cells

Characterisation of Oxidative Stress, DNA Damage and Inflammation in a Cellular Model of Parkinson’s Disease

The Protective Effects of Citrus aurantium Flower Extract against 6-Hydroxydopamine-Mediated Cell Damage in Human Neuroblastoma SH-SY5Y Cells

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