Tricetin protects against 6-OHDA-induced neurotoxicity in Parkinson's disease model by activating Nrf2/HO-1 signaling pathway and preventing mitochondria-dependent apoptosis pathway

Ren, Jie; Yuan, Ling; Wang, Wenbin; Zhang, Meiju; Wang, Qun; Li, Simin; Zhang, Ling; Hu, Kun

doi:10.1016/j.taap.2019.114617

Cited by 49 publications

(22 citation statements)

References 41 publications

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“…Following this, we further investigated molecules involved in this protective process. We found that the mRNA expression of NRF2 , which is known to induce the expression of antioxidants as well as cellular protective molecules [ 42 , 43 , 44 ], was significantly downregulated in GS hiNPCs compared to WT hiNPCs ( Figure 5 A). These results are consistent with the previous reports in various PD models [ 45 , 46 , 47 ].…”

Section: Resultsmentioning

confidence: 99%

Neuroprotective Effects of Cryptotanshinone in a Direct Reprogramming Model of Parkinson’s Disease

et al. 2020

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Parkinson’s disease (PD) is a well-known age-related neurodegenerative disease. Considering the vital importance of disease modeling based on reprogramming technology, we adopted direct reprogramming to human-induced neuronal progenitor cells (hiNPCs) for in vitro assessment of potential therapeutics. In this study, we investigated the neuroprotective effects of cryptotanshinone (CTN), which has been reported to have antioxidant properties, through PD patient-derived hiNPCs (PD-iNPCs) model with induced oxidative stress and cell death by the proteasome inhibitor MG132. A cytotoxicity assay showed that CTN possesses anti-apoptotic properties in PD-hiNPCs. CTN treatment significantly reduced cellular apoptosis through mitochondrial restoration, such as the reduction in mitochondrial reactive oxygen species and increments of mitochondrial membrane potential. These effects of CTN are mediated via the nuclear factor erythroid 2-related factor 2 (NRF2) pathway in PD-hiNPCs. Consequently, CTN could be a potential antioxidant reagent for preventing disease-related pathological phenotypes of PD.

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Section: Resultsmentioning

confidence: 99%

Neuroprotective Effects of Cryptotanshinone in a Direct Reprogramming Model of Parkinson’s Disease

et al. 2020

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“…Caspase-2 activation in response to DNA damage provides an important link between such damage and the engagement of the apoptotic pathway (Prasad et al, 2006;Harashima et al, 2014). Caspase-8 mediated the regulation of the TNFR1mediated extrinsic apoptosis pathway (Tummers and Green, 2017), and Caspase-9 is a key regulator of the mitochondrialdependent endogenous pathway (Ren et al, 2019). Caspase-9 subsequently activates Caspase-3, which is the most important executor protein in the mitochondrial-mediated apoptosis pathway, and eventually leads to inactivation of PARP (Li Z. Y. et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Dose- and Time-Dependent Cytotoxicity of Carteolol in Corneal Endothelial Cells and the Underlying Mechanisms

Zhao

Fan

2020

Front. Pharmacol.

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Carteolol is a non-selective β-adrenoceptor antagonist used for the treatment of glaucoma, and its abuse might be cytotoxic to the cornea. However, its cytotoxicity and underlying mechanisms need to be elucidated. Herein, we used an in vivo model of feline corneas and an in vitro model of human corneal endothelial cells (HCECs), respectively. In vivo results displayed that 2% carteolol (clinical dosage) could induce monolayer density decline and breaking away of feline corneal endothelial (FCE) cells. An in vitro model of HCECs that were treated dose-dependently (0.015625-2%) with carteolol for 2-28 h, resulted in morphological abnormalities, declining in cell viability and elevating plasma membrane (PM) permeability in a dose-and time-dependent manner. High-dose (0.5-2%) carteolol treatment induced necrotic characteristics with uneven distribution of chromatin, marginalization and dispersed DNA degradation, inactivated caspase-2/-8, and increased RIPK1, RIPK3, MLKL, and pMLKL expression. The results suggested that high-dose carteolol could induce necroptosis via the RIPK/MLKL pathway. While low-dose (0.015625-0.25%) carteolol induced apoptotic characteristics with chromatin condensation, typical intranucleosomal DNA laddering patterns, G 1 cellcycle arrest, phosphatidylserine (PS) externalization, and apoptotic body formation in HCECs. Meanwhile, 0.25% carteolol treatment resulted in activated caspase-2,-3,-8, and-9, downregulation of Bcl-2 and Bcl-xL, upregulation of Bax and Bad, m disruption, and release of cytoplasmic cytochrome c (Cyt.c) and AIF into the cytoplasm. These observations suggested that low-dose carteolol could induce apoptosis via a caspase activated and mitochondrial-dependent pathway. These results suggested that carteolol should be used carefully, as low as 0.015625% cartelol caused apoptotic cell death in HCECs in vitro.

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“…Therefore, in this study, the effect of the miR-30c-5p on the ROS level was investigated in HK-2 cells exposed to oxalate. The level of LdH released by cells can indicate cell oxidative damage (34). As a product of lipid peroxidation, MdA can be induced by oxidative stress and reflects the degree of oxidative injury.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of miR‑30c‑5p reduces cellular cytotoxicity and inhibits the formation of kidney stones through ATG5

et al. 2019

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MicroRNAs (miRNAs or miRs) are critical regulators in various diseases. In the current study, the role of miR-30c-5p in the formation of sodium oxalate-induced kidney stones was investigated. For this purpose, human renal tubular epithelial cells (HK-2 cells) were incubated with sodium oxalate at the concentrations of 100, 250, 500, 750 and 1,000 µM. cell viability and the miR-30c-5p expression level were respectively measured by ccK-8 assay and RT-qPcR. After separately transfecting miR-30c-5p mimic and inhibitor into the HK-2 cells, the cell apoptotic rate, the levels of mitochondrial membrane potential (MMP) and ROS were determined by flow cytometry. The levels of oxidative stress indicators [lactate dehydrogenase (LdH), malondialdehyde (MdA), superoxide dismutase (SOd) and catalase (cAT)] were determined using commercial kits. crystal-cell adhesion assay was performed to evaluate the crystal adhesion capacity in vitro. miR-30c-5p binding at autophagy related 5 (ATG5) was predicted by TargetScan7.2 and further verified by dual-luciferase reporter assay. Rescue experiments were performed to confirm the molecular mechanisms underlying sodium oxalate-induced kidney formation in HK-2 cells. The results revealed that sodium oxalate decreased the viability of HK-2 cells in a concentration-dependent manner, and that miR-30c-5p expression was significantly downregulated by exposure to 750 µM sodium oxalate. In addition, the increase in cell apoptosis and crystal number, and the upregulated levels of LdH, MdA and ROS were reversed by the overexpression of miR-30c-5p. Moreover, the overexpression of miR-30c-5p upregulated the levels of SOd, cAT and MMP induced by sodium oxalate. ATG5 was directly regulated by miR-30c-5p, and the inhibition of cell cytotoxicity and crystal-cell adhesion induced by miR-30c-5p mimic was blocked by ATG5. These data indicated that the overexpression of miR-30c-5p alleviated cell cytotoxicity and crystal-cell adhesion induced by sodium oxalate through ATG5. Thus, the current study provides a better understanding of the role of miR-30c-5p in sodium oxalate-induced kidney stones.

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Tricetin protects against 6-OHDA-induced neurotoxicity in Parkinson's disease model by activating Nrf2/HO-1 signaling pathway and preventing mitochondria-dependent apoptosis pathway

Cited by 49 publications

References 41 publications

Neuroprotective Effects of Cryptotanshinone in a Direct Reprogramming Model of Parkinson’s Disease

Neuroprotective Effects of Cryptotanshinone in a Direct Reprogramming Model of Parkinson’s Disease

Dose- and Time-Dependent Cytotoxicity of Carteolol in Corneal Endothelial Cells and the Underlying Mechanisms

Overexpression of miR‑30c‑5p reduces cellular cytotoxicity and inhibits the formation of kidney stones through ATG5

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