Inhibition of Arachidonic Acid Release by Cytosolic Phospholipase A2 Is Involved in the Antiapoptotic Effect of FK506 and Cyclosporin A on Astrocytes Exposed to Simulated Ischemia In Vitro
In the present study, we investigated whether the protective effect of FK506 and cyclosporin A (CsA) against in vitro ischemic injury of astrocytes might be mediated through attenuation of cytosolic isoform of phospholipase A2 (cPLA2) expression and activity as well as inhibition of arachidonic acid...
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doaj-e9ae2d781b7043d78b7a05fb29066d5b2020-11-25T02:20:48ZengElsevierJournal of Pharmacological Sciences1347-86132006-01-0110217787Inhibition of Arachidonic Acid Release by Cytosolic Phospholipase A2 Is Involved in the Antiapoptotic Effect of FK506 and Cyclosporin A on Astrocytes Exposed to Simulated Ischemia In VitroBozena Gabryel0Malgorzata Chalimoniuk1Anna Stolecka2Katarzyna Waniek3Jozef Langfort4Andrzej Malecki5Department of Pharmacology, Medical University of Silesia, 18 Medyków St., PL 40752 Katowice, Poland; Corresponding author. bgabryel@interia.plDepartment of Cellular Signaling, Medical Research Center, Polish Academy of Science, 5 Pawinskiego St., PL 02106 Warsaw, PolandDepartment of Physiology, Academy of Physical Education, 72A Mikolowska St., PL 40065 Katowice, PolandDepartment of Physiology, Academy of Physical Education, 72A Mikolowska St., PL 40065 Katowice, PolandDepartment of Physiology, Academy of Physical Education, 72A Mikolowska St., PL 40065 Katowice, PolandDepartment of Pharmacology, Medical University of Silesia, 18 Medyków St., PL 40752 Katowice, PolandIn the present study, we investigated whether the protective effect of FK506 and cyclosporin A (CsA) against in vitro ischemic injury of astrocytes might be mediated through attenuation of cytosolic isoform of phospholipase A2 (cPLA2) expression and activity as well as inhibition of arachidonic acid (AA) release. On the 21st day in vitro, cultures of rat astrocytes were subjected to ischemia-simulating conditions (combined oxygen glucose deprivation) for 8 h and exposed to FK506 (10 – 1000 nM) and CsA (0.25 – 10 µM). Obtained data suggest the crosstalk between the action of 0.25 – 10 µM CsA as well as 1 µM FK506 on calcineurin (CaN) and cPLA2 in anti-apoptotic signal transduction pathways. Moreover, we have shown that immunosuppressants at these concentrations protected glial cells against ischemia-induced apoptosis through the increase of cell viability, mitochondrial function restoration, and attenuation of oxidative stress. Finally, in our study, low concentrations of FK506 (10 and 100 nM) exerted limited effects on the assessed parameters. Our findings document a key role either for CaN or cPLA2 expression attenuation and AA release inhibition in the antiapoptotic effect of FK506 and CsA in ischemic astrocytes. Keywords:: FK506, cyclosporin A, astrocyte, apoptosis, cytosolic phospholipase A2http://www.sciencedirect.com/science/article/pii/S1347861319344196 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bozena Gabryel Malgorzata Chalimoniuk Anna Stolecka Katarzyna Waniek Jozef Langfort Andrzej Malecki |
spellingShingle |
Bozena Gabryel Malgorzata Chalimoniuk Anna Stolecka Katarzyna Waniek Jozef Langfort Andrzej Malecki Inhibition of Arachidonic Acid Release by Cytosolic Phospholipase A2 Is Involved in the Antiapoptotic Effect of FK506 and Cyclosporin A on Astrocytes Exposed to Simulated Ischemia In Vitro Journal of Pharmacological Sciences |
author_facet |
Bozena Gabryel Malgorzata Chalimoniuk Anna Stolecka Katarzyna Waniek Jozef Langfort Andrzej Malecki |
author_sort |
Bozena Gabryel |
title |
Inhibition of Arachidonic Acid Release by Cytosolic Phospholipase A2 Is Involved in the Antiapoptotic Effect of FK506 and Cyclosporin A on Astrocytes Exposed to Simulated Ischemia In Vitro |
title_short |
Inhibition of Arachidonic Acid Release by Cytosolic Phospholipase A2 Is Involved in the Antiapoptotic Effect of FK506 and Cyclosporin A on Astrocytes Exposed to Simulated Ischemia In Vitro |
title_full |
Inhibition of Arachidonic Acid Release by Cytosolic Phospholipase A2 Is Involved in the Antiapoptotic Effect of FK506 and Cyclosporin A on Astrocytes Exposed to Simulated Ischemia In Vitro |
title_fullStr |
Inhibition of Arachidonic Acid Release by Cytosolic Phospholipase A2 Is Involved in the Antiapoptotic Effect of FK506 and Cyclosporin A on Astrocytes Exposed to Simulated Ischemia In Vitro |
title_full_unstemmed |
Inhibition of Arachidonic Acid Release by Cytosolic Phospholipase A2 Is Involved in the Antiapoptotic Effect of FK506 and Cyclosporin A on Astrocytes Exposed to Simulated Ischemia In Vitro |
title_sort |
inhibition of arachidonic acid release by cytosolic phospholipase a2 is involved in the antiapoptotic effect of fk506 and cyclosporin a on astrocytes exposed to simulated ischemia in vitro |
publisher |
Elsevier |
series |
Journal of Pharmacological Sciences |
issn |
1347-8613 |
publishDate |
2006-01-01 |
description |
In the present study, we investigated whether the protective effect of FK506 and cyclosporin A (CsA) against in vitro ischemic injury of astrocytes might be mediated through attenuation of cytosolic isoform of phospholipase A2 (cPLA2) expression and activity as well as inhibition of arachidonic acid (AA) release. On the 21st day in vitro, cultures of rat astrocytes were subjected to ischemia-simulating conditions (combined oxygen glucose deprivation) for 8 h and exposed to FK506 (10 – 1000 nM) and CsA (0.25 – 10 µM). Obtained data suggest the crosstalk between the action of 0.25 – 10 µM CsA as well as 1 µM FK506 on calcineurin (CaN) and cPLA2 in anti-apoptotic signal transduction pathways. Moreover, we have shown that immunosuppressants at these concentrations protected glial cells against ischemia-induced apoptosis through the increase of cell viability, mitochondrial function restoration, and attenuation of oxidative stress. Finally, in our study, low concentrations of FK506 (10 and 100 nM) exerted limited effects on the assessed parameters. Our findings document a key role either for CaN or cPLA2 expression attenuation and AA release inhibition in the antiapoptotic effect of FK506 and CsA in ischemic astrocytes. Keywords:: FK506, cyclosporin A, astrocyte, apoptosis, cytosolic phospholipase A2 |
url |
http://www.sciencedirect.com/science/article/pii/S1347861319344196 |
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