title: Proteasome inhibition protects human peripheral blood mononuclear cells from radiation-induced oxidative stress.
abstract: OBJECTIVE
  The study aimed to analyze the impact of the proteasome inhibitors MG132 (N-carbobenzyoxyl-L-leucyl-L-leucyl-L-leucinal), lactacystin and celastrol on manganese superoxide dismutase (MnSOD), catalase and glutathione-S-transferase-π (GST-π), and on the heat shock protein 70 (Hsp70) in human peripheral blood mononuclear cells (PBMC), exposed to ionizing radiation.
  
  
  METHODS
  Changes in protein levels were analyzed by Western blot. Cellular viability, proteasome activity, level of oxidative stress and apoptosis were determined by standard colorimetric and fluorescence assays.
  
  
  RESULTS
  MG132 and lactacystin induced an increase in the intracellular levels of Hsp70. MnSOD was up-regulated by MG132 and celastrol, and GST-π was up-regulated by MG132 and lactacystin. Notably, the proteasome inhibitors significantly modified the protein levels in the irradiated cells and dramatically reduced the intracellular pool of oxidative species. The combined effect of radiation and proteasome inhibition was a dose-dependent up-regulation of the antioxidant enzymes and Hsp70.
  
  
  CONCLUSIONS
  All three proteasome inhibitors showed antioxidant effects in PBMC and up-regulated the antioxidant enzymes MnSOD, catalase and GST-π and the stress protein Hsp70, modifying the early radiation response, and conferring protection against the effects of ionizing radiation.
authors.affiliation: National Center of Radiobiology and Radiation Protection, 1606 Sofia, Bulgaria.
authors.forename: Katia
authors.initials: K
authors.lastname: Stankova
authors.forename: Katia
authors.initials: K
authors.lastname: Ivanova
authors.forename: Vladimir
authors.initials: V
authors.lastname: Nikolov
authors.forename: Nevena
authors.initials: N
authors.lastname: Aneva
authors.forename: Radostina
authors.initials: R
authors.lastname: Georgieva
authors.forename: Rayna
authors.initials: R
authors.lastname: Boteva
mesh_terms: D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000502:physiology* / Q000528:radiation effects; D018384:Oxidative Stress / Q000502:physiology* / Q000528:radiation effects*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000494:pharmacology*; D011829:Radiation Dosage; D011837:Radiation-Protective Agents / Q000494:pharmacology
chemical_list: D061988:Proteasome Inhibitors; D011837:Radiation-Protective Agents; D046988:Proteasome Endopeptidase Complex