title: Proteomic signatures in thapsigargin-treated hepatoma cells.
abstract: Thapsigargin, an inhibitor of the endoplasmic reticulum (ER) calcium transporters, generates Ca(2+)-store depletion within the ER and simultaneously increases Ca(2+) level in the cytosol. Perturbation of Ca(2+) homeostasis leads cells to cope with stressful conditions, including ER stress, which affect the folding of newly synthesized proteins and induce the accumulation of unfolded polypeptides and eventually apoptosis, via activation of the unfolded protein response pathway. In the present work, we analyzed the proteome changes in human hepatoma cells following acute treatment with thapsigargin. We highlighted a peculiar pattern of protein expression, marked by altered expression of calcium-dependent proteins, and of proteins involved in secretory pathways or in cell survival. For specific deregulated proteins, the thapsigargin-induced proteomic signature was compared by Western blotting to that resulting from the treatment of hepatoma cells with reducing agents or with proteasome inhibitors, to elicit endoplasmic reticulum stress by additional means and to reveal novel, potential targets of the unfolded protein response pathway.
authors.affiliation: Dipartimento di Scienze Farmaceutiche e Biomediche, Università degli Studi di Salerno , 84034 Fisciano-Salerno, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Amodio
authors.forename: Ornella
authors.initials: O
authors.lastname: Moltedo
authors.forename: Francesca
authors.initials: F
authors.lastname: Monteleone
authors.forename: Chiara
authors.initials: C
authors.lastname: D'Ambrosio
authors.forename: Andrea
authors.initials: A
authors.lastname: Scaloni
authors.forename: Paolo
authors.initials: P
authors.lastname: Remondelli
authors.forename: Nicola
authors.initials: N
authors.lastname: Zambrano
mesh_terms: D002121:Calcium Channel Blockers / Q000627:therapeutic use / Q000633:toxicity*; D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D015180:Electrophoresis, Gel, Two-Dimensional; D004721:Endoplasmic Reticulum / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism; D020543:Proteome / Q000032:analysis*; D019284:Thapsigargin / Q000627:therapeutic use / Q000633:toxicity*
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020543:Proteome; D019284:Thapsigargin