SAHA attenuates rotenone-induced toxicity in primary microglia and HT-22 cells

Günaydın, Caner; Çelik, Zülfinaz Betül; Bilge, S. Sırrı; Avcı, Bahattin; Kara, Nurten

doi:10.1177/0748233720979278

Cited by 8 publications

(7 citation statements)

References 34 publications

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“…Although SAHA did not affect the KHSRP expression, it inhibited the inflammatory response by declining the expression of iNOS, and NF-Κb through STAT3 signalling pathway inhibition. [29,30] Zhang et al [32] reported the prevention of diabetic nephropathy / diabetic kidney progression by MCC950 through NLRP3/ caspase-1/IL-1β pathway prevention or by inhibiting NLRP3 inflammasome stimulation. The inhibition of PI3K activity by quercetin in one-hour time period was also reported in chronic lymphocytic leukaemia.…”

Section: Discussionmentioning

confidence: 99%

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Possible Involvement of Cellular Pathway and Cytokines in Manganese Induced Neurotoxicity in Neuroblastoma Cells via KH–Type Splicing Regulatory Protein

Singh¹,

More²,

Latha³

et al. 2023

Pharmacogn. Res.

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Background: Manganese is a toxic essential trace element and too high concentration instigates the neurodegenerative disease known as parkinsonism. Effects of manganese may lead to apoptosis. However, a detailed mechanism of manganese toxicity has not been fully elucidated. Previous published articles have highlighted the augmentation of KHSRP expression following Mn exposure. Objectives: In this work, the importance of KHSRP in Mn-induced toxicity was checked along with the impact of other known neurotoxicity inhibitors on KHSRP. Materials and Methods: KHSRP expression, pro and anti-inflammatory cytokines, chemokines, and pharmacological inhibitors (SAHA, Quercetin, and MCC950) were determined by exposing N2a cells to various MnCl 2 concentrations. ANOVA and Dunnett's test were used to decide on the significance. Results: MnCl 2 treatment led to the augmentation of the KHSPR mRNA expression and protein increase in N2a cell line. The MnCl 2 treatment of N2a cells also showed an elevated liberation of IL-6, TNF-α, MCP-1, and IL-1β. Pharmacological agents like quercetin inhibiting PI3K, MAPK, and WNT pathways, MCC950 blocking NLRP3 pathways, and SAHA showed a decrease in KHSRP expression post Mn treatment. With the inhibition of KHSRP, a decline in the release of IL-1β, IL-6, MCP-1, and TNF-α was also observed. Conclusion: These results suggested that MnCl 2 treatment of N2a cells induce the expression of KHSRP via the PI3K-or NLRP3 pathway. Furthermore, this elevated expression of KHSRP is responsible for an increment in the liberation of pro-inflammatory markers in N2a cells. More exploration is needed to throw light on the pathway driving the KHSRP.

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Section: Discussionmentioning

confidence: 99%

“…Three pharmacological inhibitors (SAHA at 1µM, Quercetin at 60µM, and MCC950 1µM) [29][30][31][32][33][34] were tested to explore the activity of these inhibitors on MnCl 2 modulated KHSRP expression.…”

Section: Induction Of Toxicity In N2a Cell Lines By Mnclmentioning

confidence: 99%

Possible Involvement of Cellular Pathway and Cytokines in Manganese Induced Neurotoxicity in Neuroblastoma Cells via KH–Type Splicing Regulatory Protein

Singh¹,

More²,

Latha³

et al. 2023

Pharmacogn. Res.

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“…Finally, the OD values were measured at wavelength of 570 nm. In all viability experiments, 1 μM and 10 μM Rotenone dissolved in DMSO was employed as positive control [ 103 , 104 , 105 ].…”

Section: Methodsmentioning

confidence: 99%

The Autism Spectrum Disorder-Associated Bacterial Metabolite p-Cresol Derails the Neuroimmune Response of Microglial Cells Partially via Reduction of ADAM17 and ADAM10

Zheng

Prince

Marzal

et al. 2022

IJMS

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The bacterial metabolite 4-methylphenol (para-cresol or p-cresol) and its derivative p-cresyl sulfate (pCS) are elevated in the urine and feces of children with autism spectrum disorder (ASD). It has been shown that p-cresol administration induces social behavior deficits and repetitive behavior in mice. However, the mechanisms of p-cresol, specifically its metabolite pCS that can reach the brain, in ASD remain to be investigated. The pCS has been shown to inhibit LPS-stimulated inflammatory response. A Disintegrin And Metalloprotease 10 (ADAM10) and A Disintegrin And Metalloprotease 17 (ADAM17) are thought to regulate microglial immune response by cleaving membrane-bound proteins. In the present study, a neuroinflammation model of LPS-activated BV2 microglia has been used to unveil the potential molecular mechanism of pCS in ASD pathogenesis. In microglial cells pCS treatment decreases the expression or maturation of ADAM10 and ADAM17. In addition, pCS treatment attenuates TNF-α and IL-6 releases as well as phagocytosis activity of microglia. In in vitro ADAM10/17 inhibition experiments, either ADAM10 or ADAM17 inhibition reduces constitutive and LPS-activated release of TNF-α, TNFR-1 and IL-6R by microglial cells, while it increases constitutive and LPS-activated microglial phagocytotic activity. The in vivo results further confirm the involvement of ADAM10 and ADAM17 in ASD pathogenesis. In in utero VPA-exposed male mice, elevated concentration in serum of p-cresol-associated metabolites pCS and p-cresyl glucuronide (pCG) is associated with a VPA-induced increased ADAM10 maturation, and a decreased ADAM17 maturation that is related with attenuated levels of soluble TNF-α and TGF-β1 in the mice brain. Overall, the present study demonstrates a partial role of ADAM10 and ADAM17 in the derailed innate immune response of microglial cells associated with pCS-induced ASD pathogenesis.

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“…Meanwhile, TSA reduces A β plaques and oligomers by enhancing the phagocytosis of microglia and ameliorates cognitive function in APP/PS1 mice [ 131 ]. Comparably, suberoylanilide hydroxamic acid (SAHA), another pan-HDAC inhibitor, suppresses HDAC activity in microglia and reduces rotenone-induced inflammation and oxidative stress [ 133 ]. Additionally, valproic acid (VPA), a pan-HDAC inhibitor, is documented to exert neuroprotective actions in the rotenone rat model, paving the way for histone acetylation modifications of NDDs [ 134 ].…”

Section: Epigenetic Regulation Of Microglia Function and Phenotypes In Neurodegenerative Diseasesmentioning

confidence: 99%

Epigenetic Modulation of Microglia Function and Phenotypes in Neurodegenerative Diseases

Wang

Liu

et al. 2021

Neural Plasticity

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Microglia-mediated neuroinflammation is one of the most remarkable hallmarks of neurodegenerative diseases (NDDs), including AD, PD, and ALS. Accumulating evidence indicates that microglia play both neuroprotective and detrimental roles in the onset and progression of NDDs. Yet, the specific mechanisms of action surrounding microglia are not clear. Modulation of microglia function and phenotypes appears to be a potential strategy to reverse NDDs. Until recently, research into the epigenetic mechanisms of diseases has been gradually developed, making it possible to elucidate the molecular mechanisms underlying the epigenetic regulation of microglia in NDDs. This review highlights the function and phenotypes of microglia, elucidates the relationship between microglia, epigenetic modifications, and NDDs, as well as the possible mechanisms underlying the epigenetic modulation of microglia in NDDs with a focus on potential intervention strategies.

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SAHA attenuates rotenone-induced toxicity in primary microglia and HT-22 cells

Cited by 8 publications

References 34 publications

Possible Involvement of Cellular Pathway and Cytokines in Manganese Induced Neurotoxicity in Neuroblastoma Cells via KH–Type Splicing Regulatory Protein

Possible Involvement of Cellular Pathway and Cytokines in Manganese Induced Neurotoxicity in Neuroblastoma Cells via KH–Type Splicing Regulatory Protein

The Autism Spectrum Disorder-Associated Bacterial Metabolite p-Cresol Derails the Neuroimmune Response of Microglial Cells Partially via Reduction of ADAM17 and ADAM10

Epigenetic Modulation of Microglia Function and Phenotypes in Neurodegenerative Diseases

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