02717nas a2200265 4500008004100000024000700041245015900048210006900207260001800276300001200294490000700306520183100313653004202144653002802186653001802214653002202232653002302254100001802277700001602295700001802311700002202329700001602351700002402367856006002391 2023 eng d a1200aPossible Involvement of Cellular Pathway and Cytokines in Manganese Induced Neurotoxicity in Neuroblastoma Cells via KH–Type Splicing Regulatory Protein0 aPossible Involvement of Cellular Pathway and Cytokines in Mangan cFebruary 2023 a307-3140 v153 a

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 MnCl2 concentrations. ANOVA and Dunnett’s test were used to decide on the significance. Results: MnCl2 treatment led to the augmentation of the KHSPR mRNA expression and protein increase in N2a cell line. The MnCl2 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 MnCl2 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.

10aKH–type Splicing Regulatory Protein10aManganese Neurotoxicity10aNeuroblastoma10aNeurodegeneration10aNeuroinflammation.1 aSingh, Sharad1 aMore, Sunil1 aLatha, G., S.1 aAgrawal, Himanshu1 aM, Veena, S1 aNiyonzima, Francois uhttps://phcogres.com/article/2023/15/2/105530pres152033