Mitochondrial peroxiredoxin‐5 as potential modulator of mitochondria‐<scp>ER</scp> crosstalk in <scp>MPP</scp><sup>+</sup>‐induced cell death

Simoni, Stéphanie De; Linard, Dominique; Hermans, Emmanuel; Knoops, Bernard; Goemaere, Julie

doi:10.1111/jnc.12117

Cited by 55 publications

(41 citation statements)

References 67 publications

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“…Although there are several reports in the literature inducing neurotoxicity in SH-SY5Y cells with MPP + , the doses used are very different [20,21]. Based on dose-response curves, a 5 mM concentration was considered the optimal because it induced cell damage between 20 and 40 %, which is in agreement with previous studies carried out in SH-SY5Y [17].…”

Section: Discussionsupporting

confidence: 52%

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Neuroprotective Effect of JZL184 in MPP+-Treated SH-SY5Y Cells Through CB2 Receptors

et al. 2015

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Growing evidence suggests that the endocannabinoid system plays a role in neuroprotection in Parkinson's disease. Recently, we have shown the neuroprotective effect of monoacylglycerol lipase (MAGL) inhibition with JZL184 in the chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model. However, further investigation is needed to determine the neuroprotective mechanisms of the endocannabinoid system on the nigrostriatal pathway. The aim of this work was to investigate whether the neuroprotective effect of JZL184 in mice could be extended to an in vitro cellular model to further understand the mechanism of action of the drug. The SH-SY5Y cell line was selected based on its dopaminergic-like phenotype and its susceptibility to 1-methyl-4-phenylpyridinium iodide (MPP(+)) toxicity. Furthermore, SH-SY5Y cells express both cannabinoid receptors, CB1 and CB2. The present study describes the neuroprotective effect of MAGL inhibition with JZL184 in SH-SY5Y cells treated with MPP(+). The effect of JZL184 in cell survival was blocked by AM630, a CB2 receptor antagonist, and it was mimicked with JWH133, a CB2 receptor agonist. Rimonabant, a CB1 receptor antagonist, did not affect JZL184-induced cell survival. These results demonstrate that the neuroprotective effect of MAGL inhibition with JZL184 described in animal models of Parkinson's disease could be extended to in vitro models such as SH-SY5Y cells treated with MPP(+). This represents a useful tool to study mechanisms of neuroprotection mediated by MAGL inhibition, and we provide evidence for the possible involvement of CB2 receptors in the improvement of cell survival.

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Section: Discussionsupporting

confidence: 52%

“…A broad range, between 0.1 and 10 mM, of MPP + dosage has been used to induce cytotoxicity in SH-SY5Y cells [20,21]. Thus, a concentration response curve for MPP + was performed, and cell death was estimated with the LDH assay (Fig.…”

Section: Neuroprotective Effect Of Magl Inhibition With Jzl184 In Mppmentioning

confidence: 99%

Neuroprotective Effect of JZL184 in MPP+-Treated SH-SY5Y Cells Through CB2 Receptors

et al. 2015

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“…PRDX5 is part of the mitochondrial dysfunction pathway as identified by IPA and plays a major in protecting the cell from oxidative stress (De Simoni et al ., 2013). SIPA1 (Takahara et al ., 2017; Zhang et al ., 2017) and RAB3D (Yang et al ., 2003; Zhang et al ., 2015) are both involved in proliferation, invasion, and metastasis in multiple cancers, exhibiting similar functions to APE1.…”

Section: Discussionmentioning

confidence: 99%

APE1/Ref‐1 knockdown in pancreatic ductal adenocarcinoma – characterizing gene expression changes and identifying novel pathways using single‐cellRNAsequencing

et al. 2017

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Apurinic/apyrimidinic endonuclease 1/redox factor‐1 (APE1/Ref‐1 or APE1) is a multifunctional protein that regulates numerous transcription factors associated with cancer‐related pathways. Because APE1 is essential for cell viability, generation of APE1‐knockout cell lines and determining a comprehensive list of genes regulated by APE1 has not been possible. To circumvent this challenge, we utilized single‐cell RNA sequencing to identify differentially expressed genes (DEGs) in relation to APE1 protein levels within the cell. Using a straightforward yet novel statistical design, we identified 2837 genes whose expression is significantly changed following APE1 knockdown. Using this gene expression profile, we identified multiple new pathways not previously linked to APE1, including the EIF2 signaling and mechanistic target of Rapamycin pathways and a number of mitochondrial‐related pathways. We demonstrate that APE1 has an effect on modifying gene expression up to a threshold of APE1 expression, demonstrating that it is not necessary to completely knockout APE1 in cells to accurately study APE1 function. We validated the findings using a selection of the DEGs along with siRNA knockdown and qRT‐PCR. Testing additional patient‐derived pancreatic cancer cells reveals particular genes (ITGA1,TNFAIP2,COMMD7,RAB3D) that respond to APE1 knockdown similarly across all the cell lines. Furthermore, we verified that the redox function of APE1 was responsible for driving gene expression of mitochondrial genes such as PRDX5 and genes that are important for proliferation such as SIPA1 and RAB3D by treating with APE1 redox‐specific inhibitor, APX3330. Our study identifies several novel genes and pathways affected by APE1, as well as tumor subtype specificity. These findings will allow for hypothesis‐driven approaches to generate combination therapies using, for example, APE1 inhibitor APX3330 with other approved FDA drugs in an innovative manner for pancreatic and other cancer treatments.

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“…PRDX5 is an atypical, cytosolic type PRDX, which possesses more effective antioxidant activity against ROS than other PRDXs. It may confer protection against mitochondrial or nuclear DNA damage [29]. Moreover, cells with a reduced expression of PRDX5 were shown to be more prone to oxidative damage and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Quantitative proteomic analysis of gastric cancer tissue reveals novel proteins in platelet-derived growth factor B signaling pathway

et al. 2017

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Gastric cancer is one of the most common cancers in Asian countries. Searching for reliable biomarkers involving the development of gastric cancer is important for clinical practice. Quantitative proteomics has become an important method contributed to the discovery of novel diagnostic or therapeutic targets for the management of cancer. Here, we identified differently expressed proteins in gastric cancer and normal gastric tissues by using the high resolution mass spectrometer. Among the total of 2280 identified proteins, 87 were differentially expressed between gastric cancer and normal gastric tissues. Notably, several significant proteins are in the PDGF-B signaling pathway, including peroxiredoxin5 (PRDX5), S100A6, calreticulin (CALR) and cathepsin D (CTSD), which were validated by western blot. Furthermore, upstream regulators including PDGF-B, PDGFR-β, Akt, eIF4E and p70s6K were found significantly increased in the gastric cancer tissues. In addition, silencing of PRDX5 and PDGF-B suppressed the proliferation of gastric cancer cells in vitro. The administration of exogenous PDGF-BB recovered the reduced expression of PDGF-B signaling pathway in PDGF-B knockdown cells. Taken together, our findings suggested that PDGF-B signaling pathway plays an important role in the regulation of gastric cancer proliferation and the inhibition of this pathway may be a potential approach for treatment of gastric cancer.

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Mitochondrial peroxiredoxin‐5 as potential modulator of mitochondria‐ER crosstalk in MPP⁺‐induced cell death

Cited by 55 publications

References 67 publications

Neuroprotective Effect of JZL184 in MPP+-Treated SH-SY5Y Cells Through CB2 Receptors

Neuroprotective Effect of JZL184 in MPP+-Treated SH-SY5Y Cells Through CB2 Receptors

APE1/Ref‐1 knockdown in pancreatic ductal adenocarcinoma – characterizing gene expression changes and identifying novel pathways using single‐cellRNAsequencing

Quantitative proteomic analysis of gastric cancer tissue reveals novel proteins in platelet-derived growth factor B signaling pathway

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Mitochondrial peroxiredoxin‐5 as potential modulator of mitochondria‐ER crosstalk in MPP+‐induced cell death

Cited by 55 publications

References 67 publications

Neuroprotective Effect of JZL184 in MPP+-Treated SH-SY5Y Cells Through CB2 Receptors

Neuroprotective Effect of JZL184 in MPP+-Treated SH-SY5Y Cells Through CB2 Receptors

APE1/Ref‐1 knockdown in pancreatic ductal adenocarcinoma – characterizing gene expression changes and identifying novel pathways using single‐cellRNAsequencing

Quantitative proteomic analysis of gastric cancer tissue reveals novel proteins in platelet-derived growth factor B signaling pathway

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Mitochondrial peroxiredoxin‐5 as potential modulator of mitochondria‐ER crosstalk in MPP⁺‐induced cell death