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- W4377029479 abstract "<b>Abstract ID 28638</b> <b>Poster Board 101</b> <b>Objective:</b> Recent in vivo and in vitro studies have established the role of nicotine in chronic kidney diseases. However, the molecular mechanisms of how nicotine induces chronic kidney disease are still unclear. The present study tested whether acid sphingomyelinase (Asm) mediates the nicotine induced NLRP3 inflammasome activation and podocyte injury. <b>Methods and Results:</b> Confocal microscopic analysis showed that nicotine treatment increased the colocalization of NLRP3 with Asc in podocytes compared to control cells (n=6/group, p<0.05). Pretreatment with Asm inhibitor, amitriptyline abolished the nicotine-induced colocalization of NLRP3 with Asc, suggesting that Asm mediates the nicotine-induced Nlrp3 inflammasomes activation. Biochemical analysis showed that nicotine treatment significantly increased the caspase-1 activity compared to control cells. The prior treatment with amitriptyline significantly attenuated the nicotine-induced caspase-1 activity. Immunofluorescence analysis showed that nicotine treatment significantly decreased the podocin expression compared to control cells. However, prior treatment with amitriptyline attenuated the nicotine-induced podocin reduction. In addition, prior treatment with amitriptyline significantly attenuated the nicotine-induced ceramide production and Asm expression in podocytes. <b>Conclusion:</b> Based on the above results, it is concluded that Asm is one of the important mediators of nicotine-induced inflammasome activation and podocyte injury. Asm may be a therapeutic target for treatment or prevention of glomerulosclerosis associated with smoking. This work is supported by NIH R01HL148711 award" @default.
- W4377029479 created "2023-05-19" @default.
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- W4377029479 date "2023-05-18" @default.
- W4377029479 modified "2023-09-29" @default.
- W4377029479 title "Acid Sphingomyelinase Inhibitor Protects Against the Nicotine-Induced Podocyte Injury" @default.
- W4377029479 doi "https://doi.org/10.1124/jpet.122.286380" @default.
- W4377029479 hasPublicationYear "2023" @default.
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