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• W3015954736 abstract "Abstract A branched-chain polyunsaturated fatty acid, geranylgeranoic acid (GGA; C20:4), which is an endogenous metabolite derived from the mevalonate pathway in mammals, has been reported to induce cell death in human hepatoma cells. We have previously shown that the lipid-induced unfolded protein response (UPR) is an upstream cellular process for an incomplete autophagic response that might be involved in GGA-induced cell death. Here, we found that Toll-like receptor 4 (TLR4)-mediated pyroptosis in HuH-7 cells occurred by GGA treatment. The TLR4-specific inhibitor VIPER prevented both GGA-induced cell death and UPR. Knockdown of the TLR4 gene attenuated GGA-induced cell death significantly. Upon GGA-induced UPR, caspase (CASP) 4 (CASP4) was activated immediately and gasdermin D (GSDMD) was translocated concomitantly to the plasma membrane after production of the N-terminal fragment of GSDMD. Then, cellular CASP1 activation occurred following a second gradual up-regulation of the intracellular Ca2+ concentration, suggesting that GGA activated the inflammasome. Indeed, the mRNA levels of NOD-like receptor family pyrin domain containing 3 (NLRP3) and interleukin-1 β (IL1B) genes were up-regulated dramatically with translocation of cytoplasmic nuclear factor-κB (NF-κB) to nuclei after GGA treatment, indicating that GGA induced priming of the NLRP3 inflammasome through NF-κB activation. GGA-induced up-regulation of CASP1 activity was blocked by either oleic acid, VIPER, MCC950 (a selective inhibitor of the NLRP3 inflammasome), or CASP4-specific inhibitor peptide cotreatment. Pyroptotic cell death was also confirmed morphologically by bleb formation in time-series live cell imaging of GGA-treated cells. Taken together, the present results strongly indicate that GGA causes pyroptotic cell death in human hepatoma-derived HuH-7 via TLR4 signalling." @default.
• W3015954736 created "2020-04-17" @default.
• W3015954736 creator A5057751525 @default.
• W3015954736 creator A5062653186 @default.
• W3015954736 date "2020-04-01" @default.
• W3015954736 modified "2023-09-24" @default.
• W3015954736 title "TLR4-mediated pyroptosis in human hepatoma-derived HuH-7 cells induced by a branched-chain polyunsaturated fatty acid, geranylgeranoic acid" @default.
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• W3015954736 doi "https://doi.org/10.1042/bsr20194118" @default.
• W3015954736 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7189495" @default.
• W3015954736 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32270855" @default.
• W3015954736 hasPublicationYear "2020" @default.
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