Ethyl pyruvate protects SHSY5Y cells against 6-hydroxydopamine-induced neurotoxicity by upregulating autophagy

Luo, Yuening; Sakamoto, Kazuichi

doi:10.1371/journal.pone.0281957

Cited by 2 publications

(3 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have shown that increased autophagy activity helps cells resist ROS toxicity caused via mitochondrial damage [ 41 ]. Because one of the characteristic components of autophagy is the production of autophagosomes [ 42 ].…”

Section: Resultsmentioning

confidence: 99%

“…The SRG (4 µM) pretreatment group, compared with the 6-OHDA (DMSO) group, reduced the level of intracellular ROS by 73.1% (p < 0.001, Figure 3A). Previous studies have shown that increased autophagy activity helps cells resist ROS toxicity caused via mitochondrial damage [41]. Because one of the characteristic components of autophagy is the production of autophagosomes [42].…”

Section: Srg Reduces Ros Production Induced Via 6-ohda In Sh-sy5y Cel...mentioning

confidence: 99%

See 1 more Smart Citation

Syringin Prevents 6-Hydroxydopamine Neurotoxicity by Mediating the MiR-34a/SIRT1/Beclin-1 Pathway and Activating Autophagy in SH-SY5Y Cells and the Caenorhabditis elegans Model

Fu,

Hong,

Chen

2023

Cells

View full text Add to dashboard Cite

Defective autophagy is one of the cellular hallmarks of Parkinson’s disease (PD). Therefore, a therapeutic strategy could be a modest enhancement of autophagic activity in dopamine (DA) neurons to deal with the clearance of damaged mitochondria and abnormal protein aggregates. Syringin (SRG) is a phenolic glycoside derived from the root of Acanthopanax senticosus. It has antioxidant, anti-apoptotic, and anti-inflammatory properties. However, whether it has a preventive effect on PD remains unclear. The present study found that SRG reversed the increase in intracellular ROS-caused apoptosis in SH-SY5Y cells induced by neurotoxin 6-OHDA exposure. Likewise, in C. elegans, degeneration of DA neurons, DA-related food-sensitive behaviors, longevity, and accumulation of α-synuclein were also improved. Studies of neuroprotective mechanisms have shown that SRG can reverse the suppressed expression of SIRT1, Beclin-1, and other autophagy markers in 6-OHDA-exposed cells. Thus, these enhanced the formation of autophagic vacuoles and autophagy activity. This protective effect can be blocked by pretreatment with wortmannin (an autophagosome formation blocker) and bafilomycin A1 (an autophagosome–lysosome fusion blocker). In addition, 6-OHDA increases the acetylation of Beclin-1, leading to its inactivation. SRG can induce the expression of SIRT1 and promote the deacetylation of Beclin-1. Finally, we found that SRG reduced the 6-OHDA-induced expression of miR-34a targeting SIRT1. The overexpression of miR-34a mimic abolishes the neuroprotective ability of SRG. In conclusion, SRG induces autophagy via partially regulating the miR-34a/SIRT1/Beclin-1 axis to prevent 6-OHDA-induced apoptosis and α-synuclein accumulation. SRG has the opportunity to be established as a candidate agent for the prevention and cure of PD.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Srg Reduces Ros Production Induced Via 6-ohda In Sh-sy5y Cel...mentioning

confidence: 99%

Syringin Prevents 6-Hydroxydopamine Neurotoxicity by Mediating the MiR-34a/SIRT1/Beclin-1 Pathway and Activating Autophagy in SH-SY5Y Cells and the Caenorhabditis elegans Model

Fu,

Hong,

Chen

2023

Cells

View full text Add to dashboard Cite

show abstract

“…Autophagy is essential for cellular differentiation, homeostasis, and survival [ 91 , 92 ] and is conserved across evolution. Recent studies have shown that altered autophagy is involved in neuroinflammation processes in many neurological diseases, including Parkinson’s disease [ 93 , 94 ], Alzheimer’s disease [ 95 , 96 ], and neuropathic pain [ 67 , 97 , 98 ]. It was reported that autophagic activity in microglia in the spinal cord was suppressed in animals with neuropathic pain from day 2 to day 28 after nerve injury [ 99 ].…”

Section: Downstream Signaling Molecules Used By Ezh2 To Regulate Neur...mentioning

confidence: 99%

EZH2 Methyltransferase Regulates Neuroinflammation and Neuropathic Pain

Weng

Taing

Chen

et al. 2023

Cells

View full text Add to dashboard Cite

Recent studies by us and others have shown that enhancer of zeste homolog-2 (EZH2), a histone methyltransferase, in glial cells regulates the genesis of neuropathic pain by modulating the production of proinflammatory cytokines and chemokines. In this review, we summarize recent advances in this research area. EZH2 is a subunit of polycomb repressive complex 2 (PRC2), which primarily serves as a histone methyltransferase to catalyze methylation of histone 3 on lysine 27 (H3K27), ultimately resulting in transcriptional repression. Animals with neuropathic pain exhibit increased EZH2 activity and neuroinflammation of the injured nerve, spinal cord, and anterior cingulate cortex. Inhibition of EZH2 with DZNep or GSK-126 ameliorates neuroinflammation and neuropathic pain. EZH2 protein expression increases upon activation of Toll-like receptor 4 and calcitonin gene-related peptide receptors, downregulation of miR-124-3p and miR-378 microRNAs, or upregulation of Lncenc1 and MALAT1 long noncoding RNAs. Genes suppressed by EZH2 include suppressor of cytokine signaling 3 (SOCS3), nuclear factor (erythroid-derived 2)-like-2 factor (NrF2), miR-29b-3p, miR-146a-5p, and brain-specific angiogenesis inhibitor 1 (BAI1). Pro-inflammatory mediators facilitate neuronal activation along pain-signaling pathways by sensitizing nociceptors in the periphery, as well as enhancing excitatory synaptic activities and suppressing inhibitory synaptic activities in the CNS. These studies collectively reveal that EZH2 is implicated in signaling pathways known to be key players in the process of neuroinflammation and genesis of neuropathic pain. Therefore, targeting the EZH2 signaling pathway may open a new avenue to mitigate neuroinflammation and neuropathic pain.

show abstract

Ethyl pyruvate protects SHSY5Y cells against 6-hydroxydopamine-induced neurotoxicity by upregulating autophagy

Cited by 2 publications

References 47 publications

Syringin Prevents 6-Hydroxydopamine Neurotoxicity by Mediating the MiR-34a/SIRT1/Beclin-1 Pathway and Activating Autophagy in SH-SY5Y Cells and the Caenorhabditis elegans Model

Syringin Prevents 6-Hydroxydopamine Neurotoxicity by Mediating the MiR-34a/SIRT1/Beclin-1 Pathway and Activating Autophagy in SH-SY5Y Cells and the Caenorhabditis elegans Model

EZH2 Methyltransferase Regulates Neuroinflammation and Neuropathic Pain

Contact Info

Product

Resources

About