title: Tauroursodeoxycholic acid prevents stress induced aggregation of proteins in vitro and promotes PERK activation in HepG2 cells.
abstract: Tauroursodeoxycholic acid (TUDCA) a bile salt and chemical chaperone reduces stress-induced aggregation of proteins; activates PERK [PKR (RNA-dependent protein kinase)-like ER (endoplasmic reticulum) kinase] or EIF2AK3, one of the hall marks of ER stress induced unfolded protein response (UPR) in human hepatoblastoma HepG2 cells; prevents heat and dithiothreitol (DTT) induced aggregation of BSA (bovine serum albumin), and reduces ANS (1-anilino-naphthalene-8-sulfonate) bound BSA fluorescence in vitro. TUDCA inactivates heat treated, but not the native EcoR1 enzyme, and reduces heat-induced aggregation and activity of COX-1 (cyclooxygenase enzyme-1) in vitro. These findings suggest that TUDCA binds to the hydrophobic regions of proteins and prevents their subsequent aggregation. This may stabilize unfolded proteins that can mount UPR or facilitate their degradation through cellular degradation pathways.
authors.affiliation: Department of Biochemistry, University of Hyderabad, Hyderabad 500046, India.
authors.forename: Amina R
authors.initials: AR
authors.lastname: Gani
authors.affiliation: Department of Biochemistry, University of Hyderabad, Hyderabad 500046, India.
authors.forename: Jagadeesh Kumar
authors.initials: JK
authors.lastname: Uppala
authors.affiliation: Department of Biochemistry, University of Hyderabad, Hyderabad 500046, India. Electronic address: kvarsl@uohyd.ernet.in.
authors.forename: Kolluru V A
authors.initials: KV
authors.lastname: Ramaiah
mesh_terms: D051545:Cyclooxygenase 1 / Q000378:metabolism; D015246:Deoxyribonuclease EcoRI / Q000378:metabolism; D004226:Dithioerythritol / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D004789:Enzyme Activation; D056945:Hep G2 Cells / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D066329:Protein Aggregates; D012710:Serum Albumin, Bovine / Q000378:metabolism*; D013655:Taurochenodeoxycholic Acid / Q000378:metabolism*; D056811:Unfolded Protein Response; D019892:eIF-2 Kinase / Q000378:metabolism*
chemical_list: D066329:Protein Aggregates; D012710:Serum Albumin, Bovine; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D004226:Dithioerythritol; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; C460640:EIF2AK3 protein, human; D019892:eIF-2 Kinase; D015246:Deoxyribonuclease EcoRI
keywords: BSA; COX1; EcoR1; LC–MS/MS; PERK; Protein aggregation; TUDCA; UPR