TLR4-mediated pyroptosis in human hepatoma-derived HuH-7 cells induced by a branched-chain polyunsaturated fatty acid, geranylgeranoic acid.

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 transl

SUBMITTER: Yabuta S 

PROVIDER: S-EPMC7189495 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature