Identification of new modulators and protein alterations in non-apoptotic programmed cell death.
This study describes the first proteomic analysis of paraptosis--a non-apoptotic form of programmed cell death. As with apoptosis, the first description of paraptosis was based on morphological criteria. Since there are no known markers for paraptosis, the purpose of this study was to dissect changes in the proteome profile occurring during paraptosis. Using one- and two-dimensional SDS-PAGE, Western analysis, and mass spectrometry, we show that during paraptosis, alterations occur mainly in cytoskeletal proteins, signal transduction proteins, mitochondrial proteins, and some metabolic proteins. We also report the identification of: (1) a paraptosis inhibitor, phosphatidylethanolamine binding protein (PEBP-1), and (2) a candidate mediator of paraptosis, prohibitin. Identification of specific paraptotic changes will ultimately lead to tools to detect this type of programmed cell death in in vivo systems and allow for its further characterization.
Sperandio
Sabina
S
Buck Institute for Age Research, Novato, California 94945, USA.
Poksay
Karen S
KS
Schilling
Birgit
B
Crippen
Danielle
D
Gibson
Bradford W
BW
Bredesen
Dale E
DE
D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D002460:Cell Line; D019295:Computational Biology; D030562:Databases, Protein; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007150:Immunohistochemistry; D049488:Phosphatidylethanolamine Binding Protein / Q000235:genetics / Q000378:metabolism; D000091402:Prohibitins; D040901:Proteomics; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D053719:Tandem Mass Spectrometry
C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein; D000091402:Prohibitins; D012097:Repressor Proteins; D017526:Receptor, IGF Type 1