%0 Journal Article
%T Mitochondrial impairment in microglia amplifies NLRP3 inflammasome proinflammatory signaling in cell culture and animal models of Parkinson¡¯s disease
%A Adhithiya Charli
%A Anumantha G. Kanthasamy
%A Arthi Kanthasamy
%A Bharathi N. Palanisamy
%A Dharmin Rokad
%A Dilshan S. Harishchandra
%A Emir Malovic
%A Huajun Jin
%A Nikhil Panicker
%A Shivani Ghaisas
%A Souvarish Sarkar
%A Vellareddy Anantharam
%J Archive of "NPJ Parkinson's Disease".
%D 2017
%R 10.1038/s41531-017-0032-2
%X Rotenone and tebufenpyrad activate the NLRP3 inflammasome in primary murine microglia. a MTS assay of cell viability after treating lipopolysaccharide (LPS)-primed primary microglia with the mitochondrial complex-1 inhibiting pesticides rotenone (ROT) or tebufenpyrad (Tebu) (both 1£¿¦ÌM) for 24£¿h. b Luminex assay showing an increased IL-1¦Â release from LPS-primed microglia after pesticide treatments for 24£¿h. Treatment with rotenone or tebufenpyrad did not alter TNF¦Á release. c Western blot analysis of pesticide-treated, primed microglial cells showing the cleavage of pro-caspase-1 to its active form caspase-1 p20. d Duolink proximal ligation assay reveals ASC and NLRP3 interaction in pesticide-exposed, primed microglial cells but not in unprimed cells following 3£¿h of pesticide exposure. Scale bar, 15£¿¦Ìm. e ICC showing ASC speck formation in pesticide-treated primed microglial cells for 2£¿h. Scale bar, 20£¿¦Ìm. f q-RT-PCR analysis of vehicle- and rotenone-gavaged (n£¿=£¿4 each group, 30£¿mg/kg for 28 days) mice for striatal NLRP3 gene expression. g Western blot analysis for vehicle- and rotenone-gavaged (30£¿mg/kg for 28 days) mice for NLRP3, caspase-1 and IL-1¦Â. (H-K) Densitometric analysis of Western blot for NLRP3. h, caspase-1 i, caspase-1 p20 j, pro-IL-1¦Â k, and cleaved IL-1¦Â l. For all Western blots, samples derive from the same experiment and were processed in parallel. Data analyzed via Student¡¯s t test, or via two-way ANOVA with Bonferroni adjustment, *p£¿<£¿0.05, **p£¿<£¿0.01, ***p£¿<£¿0.001 and are represented as Mean£¿¡À£¿SEM with n£¿=£¿3¨C
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5645400/