title: Heat-shock inhibits protein synthesis and eIF-2 activity in cultured cortical neurons.
abstract: Stress, such as heat-shock, hypoxia and hypoglycemia, inhibits the initiation of protein synthesis. The effects of heat-shock on protein synthesis, eucaryotic initiation factor 2 (eIF-2) activity, protein kinase C (PKC), and casein kinase II (CKII) activities were studied in primary cortical neuronal cultures. In neurons exposed to heat-shock at 44 degrees C for 20 min, protein synthesis is inhibited by more than 80%, and is accompanied by a 60% decrease in eIF-2 activity. Steady state PKC and CK II activities were not affected by heat-shock. Vanadate (200 microM), a protein phosphotyrosine phosphatase inhibitor, partially prevented the depression of eIF-2 activity during heat-shock, and increased CKII activity by 90%. In contrast, staurosporine (62nM), a protein kinase C inhibitor, did not affect eIF-2 activity. We conclude that heat-shock causes a change in the phosphorylation/dephosphorylation of regulatory proteins leading to a depressed eIF-2 activity and protein synthesis in neurons.
authors.affiliation: Laboratory for Experimental Brain Research, Lund Hospital, Lund University, Sweden.
authors.forename: B R
authors.initials: BR
authors.lastname: Hu
authors.forename: Y B
authors.initials: YB
authors.lastname: Yang
authors.forename: T
authors.initials: T
authors.lastname: Wieloch
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D047388:Casein Kinases; D002478:Cells, Cultured; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D006358:Hot Temperature; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D012769:Shock / Q000378:metabolism*; D019311:Staurosporine; D014638:Vanadates / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D015852:Eukaryotic Initiation Factor-2; D009419:Nerve Tissue Proteins; D014638:Vanadates; D011494:Protein Kinases; D047388:Casein Kinases; D011493:Protein Kinase C; D019311:Staurosporine