Repeated treatments with the D1 dopamine receptor agonist SKF-38393 modulate cell viability via sustained ERK–Bad–Bax activation in dopaminergic neuronal cells

Park, Hyun Jin; Zhao, Ting; Park, Keun Hong; Lee, Myung Koo

doi:10.1016/j.bbr.2019.03.035

Cited by 5 publications

(3 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…e inhibition of ERK contributes to the increased occurrence of cell death. As an important channel in downstream of c-Met (oncogene), ERK is required for the phosphorylation of Bad, an antiapoptotic protein of Bcl-2 family [36,37]. ERK inhibitor was suggested as a potential antitumor agent [38].…”

Section: Discussionmentioning

confidence: 99%

Polyphenols from Broussonetia papyrifera Induce Apoptosis of HepG2 Cells via Inactivation of ERK and AKT Signaling Pathways

Chenzhuo

Liu

Zhang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

The extract of Broussonetia papyrifera has been proved to have antitumor activity. However, the underlying mechanism remains unclear. This study aimed to elucidate the mechanism of apoptosis of HepG2 cells induced by polyphenols from Broussonetia papyrifera (PBPs). The results revealed that PBPs inhibited the proliferation of HepG2 cells in a dose-dependent and time-dependent manner. Flow cytometry analysis showed that PBPs increased the apoptosis ratio of HepG2 cells significantly. PBPs increased intracellular reactive oxygen species (ROS) production and decreased intracellular superoxide dismutase (SOD) level of HepG2 cells. PBPs induced cell cycle arrest at G1 phase. Western blotting showed that PBPs upregulated the ratio of Bax/Bcl-2 and the expression level of Caspase-3, and activated p53 in HepG2 cells. The inhibition of proliferative relative signals (protein kinase B, PKB/AKT) and survival relative signals (extracellular signal-regulated kinase, ERK) were also observed in PBP-treated HepG2 cells. Our findings suggest that apoptosis of HepG2 cells induced by PBPs is mitochondria-mediated via inactivation of ERK and AKT signaling pathways.

show abstract

Section: Discussionmentioning

confidence: 99%

Polyphenols from Broussonetia papyrifera Induce Apoptosis of HepG2 Cells via Inactivation of ERK and AKT Signaling Pathways

Chenzhuo

Liu

Zhang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

show abstract

“…Phosphorylation of MeCP2 at Ser421 contributes to neural and behavioral responses to psychostimulants in mice, whereas phosphorylation of MeCP2 in the nucleus accumbens (NAc) is mediated by D1-like DA receptors, including DA receptors D1 (DRD1) and D5 (DRD5) ( Deng et al, 2010 ). There is growing evidence that both calcium signaling and DRD1 are involved in METH-induced neurotoxicity ( Ares-Santos et al, 2012 ; Ares-Santos et al, 2013 ; Friend and Keefe, 2013 ; Andres et al, 2015 ; Sun et al, 2015 ; Nguyen et al, 2018 ), and activation of DRD1 can significantly induce neuronal damage ( Park et al, 2019 ). Therefore, DRD1-mediated phosphorylation of MeCP2 may be a critical mechanism in METH-induced neurotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Cannabidiol prevents methamphetamine-induced neurotoxicity by modulating dopamine receptor D1-mediated calcium-dependent phosphorylation of methyl-CpG-binding protein 2

et al. 2022

View full text Add to dashboard Cite

In the past decade, methamphetamine (METH) abuse has sharply increased in the United States, East Asia, and Southeast Asia. METH abuse not only leads to serious drug dependence, but also produces irreversible neurotoxicity. Currently, there are no approved pharmacotherapies for the treatment of METH use disorders. Cannabidiol (CBD), a major non-psychoactive (and non-addictive) cannabinoid from the cannabis plant, shows neuroprotective, antioxidative, and anti-inflammatory properties under METH exposure. At present, however, the mechanisms underlying these properties remain unclear, which continues to hinder research on its therapeutic potential. In the current study, computational simulations showed that CBD and METH may directly bind to the dopamine receptor D1 (DRD1) via two overlapping binding sites. Moreover, CBD may compete with METH for the PHE-313 binding site. We also found that METH robustly induced apoptosis with activation of the caspase-8/caspase-3 cascade in-vitro and in-vivo, while CBD pretreatment prevented these changes. Furthermore, METH increased the expression of DRD1, phosphorylation of Methyl-CpG-binding protein 2 (MeCP2) at serine 421 (Ser421), and level of intracellular Ca2+in-vitro and in-vivo, but these effects were blocked by CBD pretreatment. The DRD1 antagonist SCH23390 significantly prevented METH-induced apoptosis, MeCP2 phosphorylation, and Ca2+ overload in-vitro. In contrast, the DRD1 agonist SKF81297 markedly increased apoptosis, MeCP2 phosphorylation, and Ca2+ overload, which were blocked by CBD pretreatment in-vitro. These results indicate that CBD prevents METH-induced neurotoxicity by modulating DRD1-mediated phosphorylation of MeCP2 and Ca2+ signaling. This study suggests that CBD pretreatment may resist the effects of METH on DRD1 by competitive binding.

show abstract

“…As an important molecule involved in nerve cell death, extracellular signal-regulated kinases (ERK) has sought immense attention and research. Previous study from Park and colleagues indicated that DA neurons viability regulated by D1 dopamine receptor agonist was dependent on activation of ERK-Bad-Bax pathway [5]. Meanwhile, recent research disclosed that activation of α7-nAChRs protected DA neurons from MPTP induced apoptosis through ERK/p53 signaling pathway [6].…”

Section: Introductionmentioning

confidence: 99%

AVE0991 Promotes Neuroprotection via Mas/ERK/mPTP Pathway in α-Synuclein A53T Transgenic Mice

Xue

et al. 2021

Preprint

View full text Add to dashboard Cite

Parkinson’s disease (PD) is the most prevalent neurodegenerative movement diseases featured by selective loss of dopaminergic (DA) neurons within the striatum and substantia nigra (SN). Accumulating evidence have indicated that angiotensin-(1-7) (Ang-(1-7)) prevents neuronal damage by binding to its specific receptor Mas in PD. To date, the underlying mechanisms is not known thus far. In the present study, by using α-synuclein A53T transgenic mice (A53T mice), we showed that the neuronal apoptosis in the SN of A53T mice may be attributed to a decrease in Ang-(1-7) levels. Additionally, we revealed that AVE0991, a recently found non-peptide analogue of Ang-(1−7), ameliorated neuronal apoptosis via Mas/ERK pathway in primary DA neurons. More importantly, we provided novel evidence that this beneficial impact was dependent on the suppression of mitochondrial permeability transition pore opening. In conclusion, these findings disclose the neuroprotective impact of Ang-(1−7) in the etiology of PD, and support the application of its nonpeptide analogue AVE0991 in the therapies of this neurodegenerative disease.

show abstract

Repeated treatments with the D1 dopamine receptor agonist SKF-38393 modulate cell viability via sustained ERK–Bad–Bax activation in dopaminergic neuronal cells

Cited by 5 publications

References 49 publications

Polyphenols from Broussonetia papyrifera Induce Apoptosis of HepG2 Cells via Inactivation of ERK and AKT Signaling Pathways

Polyphenols from Broussonetia papyrifera Induce Apoptosis of HepG2 Cells via Inactivation of ERK and AKT Signaling Pathways

Cannabidiol prevents methamphetamine-induced neurotoxicity by modulating dopamine receptor D1-mediated calcium-dependent phosphorylation of methyl-CpG-binding protein 2

AVE0991 Promotes Neuroprotection via Mas/ERK/mPTP Pathway in α-Synuclein A53T Transgenic Mice

Contact Info

Product

Resources

About