title: Phosphoinositid signal pathway mediate neurite outgrowth in PC12 cells by staurosporine.
abstract: OBJECTIVE
  In previous studies, we showed that staurosporine uses intracellular calcium ions to affect cell death in PC12 cells. The bulk release of intracellular excessive Ca(2+) from intracellular sources into cytosol contributes to neuronal apoptotic events, which in turn results in neuronal cell death. However, the mechanisms of Ca(2+)-induced neuronal cell death or neurite elongation is still unclear. Therefore, we investigated the relation between phosphoinositid signal pathway, intracellular calcium, and reactive oxygen species on one hand, with staurosporine-induced neurite outgrowth in PC12 cells on the other.
  
  
  RESULTS
  The inhibition of phospholipase C or IP3 receptor antagonist or phosphoinositid signal transduction antagonist produced cell death and suppressed neurite outgrowth by staurosporine in PC12 cells. The inhibition of these enzymes and pathway results in an increase in intracellular Ca(2+) although subsequent hydroxyl radical (•OH) production began after inhibitors exposure. •OH production was significantly attenuated in inhibitor supplemented medium treatment, and it was dependent on the intracellular Ca(2+) concentration. These data indicate that staurosporine activates phosphoinositid signal pathway while endoplasmic Ca(2+), and subsequent •OH production are critical events in staurosporine-induced neurite outgrowth in PC12 cells.
  
  
  CONCLUSIONS
  We conclude that the fact that staurosporine mobilizes Ca2+, probably via activating the subcellular compartment, is responsible for staurosporine-induced (Ca2+]i increase during neurite outgrowth in PC12 cells (Fig. 7, Ref. 30).
authors.forename: H
authors.initials: H
authors.lastname: Zhaleh
authors.forename: M
authors.initials: M
authors.lastname: Azadbakht
authors.forename: A Bidmeshki
authors.initials: AB
authors.lastname: Pour
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000037:antagonists & inhibitors; D016501:Neurites / Q000187:drug effects* / Q000502:physiology; D016716:PC12 Cells; D051966:Phospholipase C gamma / Q000502:physiology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D019311:Staurosporine / Q000494:pharmacology*
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D017382:Reactive Oxygen Species; D051966:Phospholipase C gamma; D019311:Staurosporine; D002118:Calcium