Pronounced alterations of cellular metabolism and structure due to hyper- or hypo-osmosis.
Cell volume alteration represents an important factor contributing to the pathology of late-onset diseases. Previously, it was reported that protein biosynthesis and degradation are inversely (trans) regulated during cell volume regulation. Upon cell shrinkage, protein biosynthesis was up-regulated and protein degradation down-regulated. Cell swelling showed opposite regulation. Recent evidence suggests a decrease of protein biodegradation activity in many neurodegenerative diseases and even during aging; both also show prominent cell shrinkage. To clarify the effect of cell volume regulation on the overall protein turnover dynamics, we investigated mouse embryonic stem cells under hyper- and hypotonic osmotic conditions using a 2-D gel based proteomics approach. These conditions cause cell swelling and shrinkage, respectively. Our results demonstrate that the adaption to altered osmotic conditions and therefore cell volume alterations affects a broad spectrum of cellular pathways, including stress response, cytoskeleton remodeling and importantly, cellular metabolism and protein degradation. Interestingly, protein synthesis and degradation appears to be cis-regulated (same direction) on a global level. Our findings also support the hypothesis that protein alterations due to osmotic stress contribute to the pathology of neurodegenerative diseases due to a 60% expression overlap with proteins found altered in Alzheimer's, Huntington's, or Parkinson's disease. Eighteen percent of the proteins altered are even shared with all three disorders.
Mao
Lei
L
Institute for Human Genetics, Charite-University Medicine Berlin, Germany, and Max Planck Institute for Molecular Genetics, Berlin, Germany.
Hartl
Daniela
D
Nolden
Tobias
T
Koppelstätter
Andrea
A
Klose
Joachim
J
Himmelbauer
Heinz
H
Zabel
Claus
C
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002853:Chromatography, Liquid; D015180:Electrophoresis, Gel, Two-Dimensional; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D009995:Osmosis; D018384:Oxidative Stress; D011506:Proteins / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
D011506:Proteins