title: Dynamics of signaling, cytoskeleton and cell cycle regulation proteins in glioblastoma cells after sub-lethal photodynamic treatment: antibody microarray study.
abstract: BACKGROUND
  Photodynamic therapy (PDT) that induces oxidative stress and cell death is used for tumor destruction in oncology. To characterize early molecular events in photosensitized glioblastoma cells, we studied expression of 224 proteins after sublethal PDT that doesn't kill but wounds cells.
  
  
  METHODS
  Cultured glioblastoma D54Mg cells were photosensitized with 5-aminolevulinic acid so that cell survival was 95-100%. At following 0.5-5.5h protein expression and phosphorylation was assayed using proteomic antibody microarrays.
  
  
  RESULTS
  Within the first post-treatment hour we observed phosphorylation of protein kinase Raf, adhesion-related kinases FAK and Pyk2, and microtubule-associated protein tau. Protein kinase Cγ and microtubule-associated protein MAP-1B were overexpressed. Dystrophin, calponin, and vinculin, components of the actin cytoskeleton scaffold, microtubule-associated proteins MAP2 and CNP, cytokeratins 4 and 7 were down-regulated that indicated changes in adhesion and cell shape. Down-regulation of cyclins A, D1 and D3, c-Myc, checkpoint proteins chk1/2 and up-regulation of Smad4 could arrest the cell cycle. Overexpression of Bcl-xL and down-regulation of caspase 9 demonstrated anti-apoptotic response. At 2h post-treatment protein expression changed lesser but at 5.5h levels of PKCγ and β-synuclein and phosphorylation of Raf, FAK, Pyk2, and tau increased again.
  
  
  CONCLUSIONS
  Sub-lethal PDT induces complex response of glioblastoma cells including changes in activity and expression of proteins involved in adhesion-mediated signaling, signal transduction, cytoskeleton remodeling, cell cycle regulation and anti-apoptotic processes.
  
  
  CONCLUSIONS
  Multiple reactions of various cellular subsystems including adhesion, cytoskeleton, signal transduction, cell cycle, and apoptosis are integrated into the general cell response to a sublethal impact.
authors.affiliation: Department of Biophysics, Southern Federal University, Stachky 194/1, 344090, Rostov-on-Don, Russia. auzd@yandex.ru
authors.forename: Anatoly
authors.initials: A
authors.lastname: Uzdensky
authors.forename: Bjorn
authors.initials: B
authors.lastname: Kristiansen
authors.forename: Johan
authors.initials: J
authors.lastname: Moan
authors.forename: Asta
authors.initials: A
authors.lastname: Juzeniene
mesh_terms: D000622:Aminolevulinic Acid / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D040081:Protein Array Analysis; D040901:Proteomics; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D018797:Cell Cycle Proteins; D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid