Protective effect of SIRT1 on toxicity of microglial-derived factors induced by LPS to PC12 cells via the p53-caspase-3-dependent apoptotic pathway

Ye, Jie-ming; Liu, Zhenhua; Wei, Ji-peng; Lu, Lingli; Huang, Yanjun; Luo, Lili; Xie, Huifang

doi:10.1016/j.neulet.2013.08.020

Cited by 84 publications

(64 citation statements)

References 15 publications

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“…These findings are somewhat in alignment with previous reports investigating LPS activation in microglial cells, in particular for elevation of MIP-2, TNF-alpha, IL-1a, IL-6, MIP-1a, MCP-1 and GCSF, NO, inducible nitric oxide synthase (iNOS) (Soliman et al, 2013) where others report elevation of additional pro-inflammatory markers such as free radicals, osteopontin (Hasegawa-Ishii, Takei, 2011, Mayer et al, 2011), IL-1beta (Ye et al, 2013), PGE2 (Kim et al, 2013b) and increased the levels of cyclooxygenase (Cox) 1 and 2 (Soliman, et al 2013). In general pro-inflammatory processes associated with activated BV-2 microglial cells involved a number of signaling pathways that involve Src-MEK1/2-ERK1/2 (Manivannan et al, 2013, Yeh et al, 2013) p38MAPK phosphorylation (Kim et al, 2013a), phosphorylation of c-Jun N-terminal kinase and the nuclear translocation of NF-kappaB p65 (Jung et al, 2013, More et al, 2013) /activation of NFkappaB-signaling pathway (Yeh, Yang, 2013) or down-regulation of HO-1 / and PKA-mediated CREB phosphorylation.…”

Section: Discussionsupporting

confidence: 90%

Anti-inflammatory effects of thymoquinone in activated BV-2 microglial cells

Taka

Mazzio

Goodman

et al. 2015

Journal of Neuroimmunology

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Thymoquinone (TQ), the main pharmacological active ingredient within the black cumin seed (Nigella sativa) is believed to be responsible for therapeutic effects on chronic inflammatory conditions such as arthritis, asthma and neurodegeneration. In this study, we evaluated the potential anti-inflammatory role of TQ in lipopolysaccharide (LPS)-stimulated BV-2 murine microglia cells. The results obtained indicated that TQ was effective in reducing NO2- with an IC50 of 5.04 μM, relative to selective iNOS inhibitor LNIL- L-N6-(1-Iminoethyl)lysine (IC50 4.09 μM). TQ mediated reduction in NO2- was found to parallel the decline of iNOS protein expression as confirmed by immunocytochemistry. In the next study, we evaluated the anti-inflammatory effects of TQ on ninety – six (96) cytokines using a RayBio AAM-CYT-3 and 4 cytokine antibody protein array. Data obtained establish a baseline protein expression profile characteristic of resting BV-2 cells in the order of osteopontin > MIP-1alpha > MIP-1g > IGF-1 and MCP-I. In the presence of LPS [1ug/ml], activated BV-2 cells produced a sharp rise in specific pro-inflammatory cytokines/chemokine’s IL-6, IL-12p40/70, CCL12 /MCP-5, CCL2 / MCP-1, and G-CSF which were attenuated by the addition of TQ (10μM). The TQ mediated attenuation of MCP-5, MCP-1 and IL-6 protein in supernatants from activated BV-2 cells were corroborated by independent ELISA and mRNA expression profiling using RT2 Profiler PCR cytokine arrays. Moreover, the data obtained from the RT2 PCR demonstrated a similar pattern where the LPS mediated elevation of mRNA for IL-6, CCL12 /MCP-5, CCL2 / MCP-1 were significantly attenuated by TQ (10μM). Also, in this study, consistent data were obtained for both protein antibody array densitometry and ELISA assays. In addition, TQ was found to reduce LPS mediated elevation in gene expression of Cxcl10 and a number of other cytokines in the panel. These findings demonstrate the significant anti-inflammatory properties of TQ in LPS activated microglial cells. Therefore, the obtained results might indicate the usefulness of TQ in delaying the onset of inflammation-mediated neurodegenerative disorders involving activated microglia cells.

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Section: Discussionsupporting

confidence: 90%

Anti-inflammatory effects of thymoquinone in activated BV-2 microglial cells

Taka

Mazzio

Goodman

et al. 2015

Journal of Neuroimmunology

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“…Moreover, BV-2 cells have been suggested to phagocytose 'live' PC12 cells when activated with LPS (McArthur et al, 2010) or PMA , although it was not tested whether the PC12 were in fact alive when phagocytosed, or whether blocking phagocytosis prevented cell death. Because LPS-activated BV-2 cells produce nitric oxide (NO) from inducible NO synthase (iNOS, also known as NOS2) (Choi and Park, 2012), NO can induce apoptosis of PC12 cells (Bal-Price and Brown, 2000) and supernatants from activated BV-2 cells can induce apoptosis of PC12 cells (Ye et al, 2013), it might be that BV-2 microglia simply induce apoptosis of co-cultured PC12 cells. We therefore decided to use this system to investigate whether activated microglia could kill the PC12 cells by (1) apoptosis, (2) phagocytosis of dead cells or (3) phagocytosis of reversibly apoptotic cells.…”

Section: Introductionmentioning

confidence: 99%

Activated microglia cause reversible apoptosis of pheochromocytoma cells, inducing their cell death by phagocytosis

Hornik

Vilalta

Brown

2016

Journal of Cell Science

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Some apoptotic processes, such as phosphatidylserine exposure, are potentially reversible and do not necessarily lead to cell death. However, phosphatidylserine exposure can induce phagocytosis of a cell, resulting in cell death by phagocytosis: phagoptosis. Phagoptosis of neurons by microglia might contribute to neuropathology, whereas phagoptosis of tumour cells by macrophages might limit cancer. Here, we examined the mechanisms by which BV-2 microglia killed co-cultured pheochromocytoma (PC12) cells that were either undifferentiated or differentiated into neuronal cells. We found that microglia activated by lipopolysaccharide rapidly phagocytosed PC12 cells. Activated microglia caused reversible phosphatidylserine exposure on and reversible caspase activation in PC12 cells, and caspase inhibition prevented phosphatidylserine exposur and decreased subsequent phagocytosis. Nitric oxide was necessary and sufficient to induce the reversible phosphatidylserine exposure and phagocytosis. The PC12 cells were not dead at the time they were phagocytised, and inhibition of their phagocytosis left viable cells. Cell loss was inhibited by blocking phagocytosis mediated by phosphatidylserine, MFG-E8, vitronectin receptors or P2Y 6 receptors. Thus, activated microglia can induce reversible apoptosis of target cells, which is insufficient to cause apoptotic cell death, but sufficient to induce their phagocytosis and therefore cell death by phagoptosis.

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“…The level of SIRT1 in dopaminergic neurons is significantly down-regulated in toxic models of PD [8–10]. Caloric restriction, glucose analogue or resveratrol, which activate SIRT1, could alleviate the loss and injury of dopaminergic neurons in PD models [11,12]. Overexpression of SIRT1 has been shown to suppress the formation of a-synuclein aggregates by activating molecular chaperones in animal and cell models [13,14].…”

Section: Introductionmentioning

confidence: 99%

The epigenetic regulation of HIF-1α by SIRT1 in MPP + treated SH-SY5Y cells

Dong

Guo

Feng

et al. 2016

Biochemical and Biophysical Research Communications

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Both silent information regulator 1 (SIRT1) and hypoxia inducible factor 1 (HIF-1) have been found to play important roles in the pathophysiology of Parkinson’s disease (PD). However, their mechanisms and their relationship still require further study. In the present study, we focused on the change and relationship of SIRT1 and HIF-1α in PD. PD cell models were established by using methyl-4-phenylpyridinium (MPP+), which induced inhibition of cell proliferation, cell cycle arrest and apoptosis. We found that the expression of HIF-1α and its target genes VEGFA and LDHA increased and that SIRT1 expression was inhibited in MPP+ treated cells. With further analysis, we found that the acetylation of H3K14 combined with the HIF-1α promoter was dramatically increased in cells treated with MPP+, which resulted in the transcriptional activation of HIF-1α. Moreover, the acetylation of H3K14 and the expression of HIF-1α increased when SIRT1 was knocked down, suggesting that SIRT1 was involved in the epigenetic regulation of HIF-1α. At last, phenformin, another mitochondrial complex1 inhibitor, was used to testify that the increased HIF-1a was not due to off target effects of MPP+. Therefore, our results support a link between PD and SIRT1/HIF-1α signaling, which may serve as a clue for understanding PD.

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Protective effect of SIRT1 on toxicity of microglial-derived factors induced by LPS to PC12 cells via the p53-caspase-3-dependent apoptotic pathway

Cited by 84 publications

References 15 publications

Anti-inflammatory effects of thymoquinone in activated BV-2 microglial cells

Anti-inflammatory effects of thymoquinone in activated BV-2 microglial cells

Activated microglia cause reversible apoptosis of pheochromocytoma cells, inducing their cell death by phagocytosis

The epigenetic regulation of HIF-1α by SIRT1 in MPP + treated SH-SY5Y cells

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