20.500.12556/DiRROS-18532 Staurosporine induces different cell death forms in cultured rat astrocytes Background. Astroglial cells are frequently involved in malignant transformation. Besides apoptosis, necroptosis, a different form of regulated cell death, seems to be related with glioblastoma genesis, proliferation, angiogenesis and invasion. In the present work we elucidated mechanisms of necroptosis in cultured astrocytes, and compared them with apoptosis, caused by staurosporine. Materials and methods. Cultured rat cortical astrocytes wereused for a cell death studies. Cell death was induced by different concentrations of staurosporine, and modified by inhibitors of apoptosis (z-vad-fmk) and necroptosis (nec-1). Different forms of a cell death were detected using flow cytometry.Results. We showed that staurosporine, dependingon concentration, induces both, apoptosis as well as necroptosis.Treatment with 10-7 M staurosporine increased apoptosis of astrocytes after the regeneration in a staurosporine free medium. When caspases were inhibited, apoptosis was attenuated, while necroptosis was slightly increased. Treatment with 10-6 M staurosporine induced necroptosis that occurred after the regeneration of astrocytes in a staurosporine free medium, as well as without regeneration period. Necroptosis was significantly attenuated by nec-1 which inhibits RIP1 kinase. On the other hand, the inhibition of caspases had no effect on necroptosis. Furthermore, staurosporine activated RIP1 kinase increased the production of reactive oxygen species, while an antioxidant BHA significantly attenuated necroptosis.Conclusion. Staurosporine can induce apoptosis and/or necroptosis in cultured astrocytes via different signalling pathways. Distinction between different forms of cell death is crucial in the studies of therapy-induced necroptosis. astrociti reaktivni kisik citometrija true false true Association of Radiology and Oncology Ljubljana Angleški jezik Slovenski jezik by Authors Neznano 2024-03-22 08:51:24 2024-03-22 08:51:24 2024-03-23 03:37:31 0000-00-00 00:00:00 2012 0 0 BSDOCID164785; str. 312-320, III no. 4 Vol. 46 dec. 2012 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2012-12-01 616-006 1318-2099 10.2478/v10019-012-0036-9 29979865 RAZ_Simenc_Janez_2012.pdf RAZ_Simenc_Janez_2012.pdf 1 E3799EF3F7D3A276015EAF4DB6F3CD8B c104286c75718af497ec73a128810afce92d973afaeea339dd186beb8fc2fd34 213ce6fc-e821-11ee-9dd4-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=25255 Onkološki inštitut Ljubljana 0 0 0