Proteomic analysis of the reactive phenotype of astrocytes following endothelin-1 exposure.
Reactive gliosis is an invariant feature of the pathology of central nervous system (CNS) injury and a major determinant of neuronal survival and regeneration. To begin to understand the alterations in astrocyte protein expression that drive glial changes that occur following injury, we used an established model system (endothelin-1 stimulation of hypertrophy) and proteomic analysis to define a discrete set of differentially expressed proteins and post-translational modifications that occur as the astrocytes change from a quiescent to a reactive state. This orchestrated set of changes included proteins involved in cytoskeletal reorganization (caldesmon, calponin, alpha B-crystallin, stathmin, collapsing response mediator protein-2), cell adhesion (vinculin, galectin-1), signal transduction (RACK-1) and astrocyte differentiation (glutamine synthetase). Using proteomic analysis to understand what drives astrocyte expression of these functionally divergent molecules may offer insight into the mechanisms by which astrocytes can exhibit both pro-regenerative and anti-regenerative activities following CNS injury.
Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Gregory F
GF
Egnaczyk
James D
JD
Pomonis
Julie A
JA
Schmidt
Scott D
SD
Rogers
Christopher
C
Peters
Joseph R
JR
Ghilardi
Patrick W
PW
Mantyh
John E
JE
Maggio
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D015153:Blotting, Western; D048429:Cell Size; D002478:Cells, Cultured; D015180:Electrophoresis, Gel, Two-Dimensional; D019332:Endothelin-1 / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry; D009416:Nerve Regeneration / Q000235:genetics / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D010641:Phenotype; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D040901:Proteomics / Q000379:methods*; D051381:Rats; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D019332:Endothelin-1; D009419:Nerve Tissue Proteins