The protein l-isoaspartyl (d-aspartyl) methyltransferase protects against dopamine-induced apoptosis in neuroblastoma SH-SY5Y cells

Ouazia, Dahmane; Levros, Louis‐Charles; Rassart, Éric; Desrosiers, Richard R.

doi:10.1016/j.neuroscience.2015.03.026

Cited by 24 publications

(20 citation statements)

References 55 publications

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“…This result is consistent with those previously reported by Ouazia et al. (2015), which showed an increase of ROS when NB cells were treated with DA . The dose‐dependent increase in ROS positively correlates with cell death among NB cells when treated with Tolcapone, providing support for ROS production as one mechanism by which Tolcapone is toxic to NB cells.…”

Section: Discussionsupporting

confidence: 92%

“…In a Parkinson's study evaluating a neuroprotectant, Ouazia et al. (2015) indicated that treatment of a NB cell line (SH‐SY5Y) with DA stimulated the levels of proapoptotic proteins such as cleaved caspase 3 and p53, which causes cell cycle arrest . This study additionally showed that when these NB cells were pretreated with antioxidants prior to DA treatment, cleaved caspase‐9 activation was prevented, indicating that apoptosis via accumulation of dopamine is ROS‐dependent in NB cells .…”

Section: Introductionmentioning

confidence: 91%

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Tolcapone induces oxidative stress leading to apoptosis and inhibition of tumor growth in Neuroblastoma

et al. 2017

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Catechol-O-methyltransferase (COMT) is an enzyme that inactivates dopamine and other catecholamines by O-methylation. Tolcapone, a drug commonly used in the treatment of Parkinson's disease, is a potent inhibitor of COMT and previous studies indicate that Tolcapone increases the bioavailability of dopamine in cells. In this study, we demonstrate that Tolcapone kills neuroblastoma (NB) cells in preclinical models by inhibition of COMT. Treating four established NB cells lines (SMS-KCNR, SH-SY5Y, BE(2)-C, CHLA-90) and two primary NB cell lines with Tolcapone for 48 h decreased cell viability in a dose-dependent manner, with IncuCyte imaging and Western blotting indicating that cell death was due to caspase-3-mediated apoptosis. Tolcapone also increased ROS while simultaneously decreasing ATP-per-cell in NB cells. Additionally, COMT was inhibited by siRNA in NB cells and showed similar increases in apoptotic markers compared to Tolcapone. In vivo xenograft models displayed inhibition of tumor growth and a significant decrease in time-to-event in mice treated with Tolcapone compared to untreated mice. These results indicate that Tolcapone is cytotoxic to neuroblastoma cells and invite further studies into Tolcapone as a promising novel therapy for the treatment of neuroblastoma. Cancer Medicine Open Access 1342

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 91%

Tolcapone induces oxidative stress leading to apoptosis and inhibition of tumor growth in Neuroblastoma

et al. 2017

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“…Previous studies have showed that ROS generated by DA were able to inhibit the transcriptional activity of the human PCMT1 gene 9 . Accordingly, PCMT1 overexpression conferred antioxidant properties protecting cell components against the ROS generated by cytosolic DA 8 . The antioxidant effects of CGP3466B observed in the present study probably result from PCMT1 overexpression.…”

Section: Discussionmentioning

confidence: 94%

“…Recently, the anti-apoptotic properties of PCMT1have been explored in brain cells 7 – 9 , endothelial cells 10 and cardiomyocytes in vitro 11 . In addition, PCMT1 expression could have antioxidant properties against the reactive oxygen species (ROS) generated by cytosolic dopamine 8 .…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effects of CGP3466B on Apoptosis Are Modulated by Protein-L-isoaspartate (D-aspartate) O-methyltransferase/Mst1 Pathways after Traumatic Brain Injury in Rats

Liang

Shi

Zheng

et al. 2017

Sci Rep

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Neuronal apoptosis chiefly contributes to the cell loss following traumatic brain injury (TBI). CGP3466B is a compound related to the anti-Parkinsonism drug R-(−)-deprenyl. Previous studies have illuminated anti-apoptosis effects of CGP3466B in different cell lines, but the underlying mechanisms have not been fully elucidated. Mammalian sterile 20 (STE20)-like kinase1 (Mst1) is a core component of the Hippo signaling pathway. Protein-L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1) is an enzyme that repairs damaged L-isoaspartyl residues in proteins. The present study was performed to investigate the neuroprotective effects of CGP3466B and to determine a potential PCMT1/Mst1 neuronal anti-apoptotic pathway after TBI. Double immunofluorescence staining demonstrated that PCMT1 and Mst1 are co-located in neurons. Administration of CGP3466B improved neurological function, downregulated the ROS level and alleviated brain edema at 24 h after TBI. CGP3466B alleviates neuronal apoptosis by increasing PCMT1 expression and subsequently inhibiting MST1 activation, resulting in changing the expression levels of Bax, Bcl-2 and active-caspase3. The TUNEL staining results also support the anti-apoptosis effects of CGP3466B. The anti-apoptotic effects of CGP3466B were abolished by chelerythrine, an Mst1 activator, without changing PCMT1 levels. In conclusion, our findings suggest CGP3466B may have a promising therapeutic potential by modulating PCMT1/Mst1 signaling pathway after TBI injury.

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“…Parkinson's disease (PD), the second most common neurodegenerative disease in older individuals, usually manifested as a range of activities, including dyskinesia or neurobiological disorders, such as bradykinesia, resting tremor, and muscle stiffness (Abbas, Xu, & Tan, ), prominent traits of which include dopaminergic cells loss within the substantia nigra pars compacta (SNpc; Wirdefeldt, Adami, Cole, Trichopoulos, & Mandel, ) and the aberrant intracellular protein aggregation including α‐synuclein (Sun, Zhang, Huang, & Chen, ). It has been suggested that PD pathogenesis has been implicated to neuronal apoptosis caused by impaired mitochondrial function (Ouazia, Levros, Rassart, & Desrosiers, ), so the study of neuronal apoptosis may provide a new target for the treatment of PD (Ghavami et al, ). 1‐Methyl‐4‐Phenyl‐pyridinium Iodide (MPP(+)), a commonly used dopamine (DA) neuron toxicant, can cause mitochondrial dysfunction (Nakamura et al, ), inducing reactive oxygen species (ROS) pathway activation, eventually leading to cell apoptosis, and is therefore commonly used to simulate PD in vitro model (Suzuki, Mizuno, & Yoshida, ).…”

Section: Introductionmentioning

confidence: 99%

miR‐30b protects nigrostriatal dopaminergic neurons from MPP(+)‐induced neurotoxicity via SNCA

et al. 2020

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Objective To explore the function of miR‐30b in pathogenesis of Parkinson's disease (PD) and its underlying molecular mechanism. Materials and Methods We used 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPP(+)) as a tool for constructing the PD cell model, using miR‐30b mimics or inhibitors to manipulate miR‐30b level for an experimental model of acquisition. The cell viability of SH‐SY5Y was detected by CCK, and luciferase was used to screen the binding of target genes. The protein levels of SNCA were measured by Western blot. Then, we investigate the changes in pro‐ and anti‐apoptotic markers with or without miR‐30b treatment. Results There was a significant low expression of MiR‐30b in MPP(+)‐induced cells. SH‐SY5Y cell viability was rescued by MiR‐30b overexpression. Luciferase experiments showed that MiR‐30b may bind to the 3′‐UTR side of SNCA and inhibited its expression. By Western blot, the SNCA level was markedly decreased by miR‐30b. miR‐30b attenuated the upregulation of Bax and the depletion of Bcl‐2 induced by MPP(+).

show abstract

The protein l-isoaspartyl (d-aspartyl) methyltransferase protects against dopamine-induced apoptosis in neuroblastoma SH-SY5Y cells

Cited by 24 publications

References 55 publications

Tolcapone induces oxidative stress leading to apoptosis and inhibition of tumor growth in Neuroblastoma

Tolcapone induces oxidative stress leading to apoptosis and inhibition of tumor growth in Neuroblastoma

Neuroprotective Effects of CGP3466B on Apoptosis Are Modulated by Protein-L-isoaspartate (D-aspartate) O-methyltransferase/Mst1 Pathways after Traumatic Brain Injury in Rats

miR‐30b protects nigrostriatal dopaminergic neurons from MPP(+)‐induced neurotoxicity via SNCA

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