title: Staurosporine Induces Platelet Apoptosis Through p38 Mitogen-Activated Protein Kinase Signaling Pathway.
abstract: BACKGROUND
  Staurosporine (STS), a microbial alkaloid and potent PKC inhibitor, has become one of the most promising anti-cancer drugs. STS effectively induces apoptosis in many nucleated cells; however, it is still unclear whether STS induces apoptosis in enucleated platelets.
  
  
  METHODS
  Apoptotic events in platelets treated with STS were assessed by flow cytometry or western blotting.
  
  
  RESULTS
  STS induced depolarization of mitochondrial inner transmembrane potential (ΔΨm), up-regulation of Bax and Bak, phosphatidylserine (PS) exposure, release of mitochondrial cytochrome c, and activation of caspase-8 and caspase-9 in human platelets. Furthermore, STS stimulation induced phosphorylation of p38 mitogen-activated protein kinase (MAPK). Inhibition of p38 MAPK activation significantly reduced ΔΨm depolarization and PS exposure in platelets stimulated with STS.
  
  
  CONCLUSIONS
  These data indicate that STS induces platelet apoptosis via the p38 MAPK signaling pathway. These findings suggest that platelet apoptosis-related hemorrhage should be noticed in STS and its derivatives in clinical tests.
authors: Lili
authors: L
authors: Zhao
authors: Guoyuan
authors: G
authors: Lu
authors: Qing
authors: Q
authors: Zhao
authors: Mingyi
authors: M
authors: Zhang
authors: Mengxing
authors: M
authors: Chen
authors: Jiansheng
authors: J
authors: Zhang
authors: Kesheng
authors: K
authors: Dai
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D019311:Staurosporine / Q000633:toxicity*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D047428:Protein Kinase Inhibitors; D048051:p38 Mitogen-Activated Protein Kinases; D019311:Staurosporine