The Proteome Response to Amyloid Protein Expression In Vivo

• DOI: 10.1371/journal.pone.0050123
• Publication Date: 2012-11-21T22:59:46Z
• Authors: Ricardo A. Gomes; Catarina Franco; Gonçalo Da Costa; Sébastien Planchon; Jenny Renaut; Raquel M. Ribeiro; Francisco Pinto; Marta Sousa Silva; Ana Varela Coelho; Ana Ponces Freire; Carlos Cordeiro
• Keywords: Proteome; Amyloid disease; Amyloid (mycology); Proteostasis

Protein misfolding disorders such as Alzheimer, Parkinson and transthyretin amyloidosis are characterized by the formation of protein amyloid deposits. Although nature location aggregated proteins varies between different diseases, they all share similar molecular pathways unfolding, aggregation deposition. Most effects these likely to occur at proteome level, a virtually unexplored reality. To investigate an expression on cellular proteome, we created yeast system using human (TTR) model amyloidogenic protein. We used Saccharomyces cerevisiae, living test tube, express native TTR (non-amyloidogenic) variant L55P, later forming aggregates when expressed in yeast. Differential changes were quantitatively analyzed 2D-differential gel electrophoresis (2D-DIGE). show that TTR-L55P causes metabolic shift towards energy production, increased superoxide dismutase well several chaperones involved refolding. Among chaperones, members HSP70 family peptidyl-prolyl-cis-trans isomerase (PPIase) identified. The latter is highly relevant considering it was previously found be interacting partner plasma ATTR patients but not healthy or asymptomatic subjects. small ubiquitin-like modifier (SUMO) also increased. Our findings suggest refolding degradation activated, causing demand energetic resources, thus shift. Additionally, oxidative stress appears consequence process, posing enhanced threat cell survival.