<abstract xmlns="http://www.w3.org/1999/xhtml">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 were used 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, depending on 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.</abstract>

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 were used 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, depending on 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.

Staurosporine induces different cell death forms in cultured rat astrocytes

University of Ljubljana, Faculty of Medicine, Ljubljana, Slovenia

University of Maribor, Faculty of Medicine, Maribor, Slovenia

Radiology and Oncology

{"article-title":"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,...

Staurosporine induces different cell death forms in cultured rat astrocytes

Published Online: Nov 09, 2012

Page range: 312 - 320

Received: Mar 22, 2012

Accepted: May 18, 2012

DOI: https://doi.org/10.2478/v10019-012-0036-9

Keywords
astrocytes, staurosporine, necroptosis, apoptosis, reactive oxygen species, flow cytometry

This content is open access.

Staurosporine induces different cell death forms in cultured rat astrocytes

Published Online: Nov 09, 2012

Page range: 312 - 320

Received: Mar 22, 2012

Accepted: May 18, 2012

DOI: https://doi.org/10.2478/v10019-012-0036-9

Keywordsastrocytes, staurosporine, necroptosis, apoptosis, reactive oxygen species, flow cytometry

This content is open access.

Keywords
astrocytes, staurosporine, necroptosis, apoptosis, reactive oxygen species, flow cytometry