Metformin limits apoptosis in primary rat cortical astrocytes subjected to oxygen and glucose deprivation
Metformin, a type 2 anti-diabetic drug and an activator of AMP-activated protein kinase (AMPK), has been shown to reduce infarct size and pathological changes affecting astroglia in animal models of ischemic stroke. In this study, we evaluated how metformin affects cell viability, apoptosis and dete...
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| Format: | Article |
| Language: | English |
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Termedia Publishing House
2018-12-01
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| Series: | Folia Neuropathologica |
| Subjects: | |
| Online Access: | https://www.termedia.pl/Metformin-limits-apoptosis-in-primary-rat-cortical-astrocytes-subjected-to-oxygen-and-glucose-deprivation,20,34468,1,1.html |
| _version_ | 1831808411199602688 |
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| author | Bożena Gabryel Sebastian Liber |
| author_facet | Bożena Gabryel Sebastian Liber |
| author_sort | Bożena Gabryel |
| collection | DOAJ |
| description | Metformin, a type 2 anti-diabetic drug and an activator of AMP-activated protein kinase (AMPK), has been shown to reduce infarct size and pathological changes affecting astroglia in animal models of ischemic stroke. In this study, we evaluated how metformin affects cell viability, apoptosis and determined the role of AMPK, as well as JNK p46/p54 and p38 kinases, in the observed phenomena in the culture of primary rat cortical astrocytes subjected to 12 h of oxygen and glucose deprivation (OGD). Metformin improved cell viability, reduced the fraction of apoptotic nuclei, and inhibited the activation of the executive caspase-3. Decreased activation of JNK p54 and p38 was associated with increased Bcl-XL expression and decreased mitochondrial leakage of cytochrome c. However, only cell viability and partially the fraction of apoptotic nuclei varied concomitantly with changes in AMPK activity, suggesting that AMPK is critical for metformin-mediated effects and regulates programmed cell death in a caspase-independent manner. Experiments with the inhibitors of JNK and p38 supports the role of these kinases in the drug-related inhibition of mitochondrial and extrinsic pathway of apoptosis. |
| first_indexed | 2024-12-22T20:23:42Z |
| format | Article |
| id | doaj.art-cb5009b84668449b8ccf7f9e728e149d |
| institution | Directory Open Access Journal |
| issn | 1641-4640 1509-572X |
| language | English |
| last_indexed | 2024-12-22T20:23:42Z |
| publishDate | 2018-12-01 |
| publisher | Termedia Publishing House |
| record_format | Article |
| series | Folia Neuropathologica |
| spelling | doaj.art-cb5009b84668449b8ccf7f9e728e149d2022-12-21T18:13:47ZengTermedia Publishing HouseFolia Neuropathologica1641-46401509-572X2018-12-0156432833610.5114/fn.2018.8086634468Metformin limits apoptosis in primary rat cortical astrocytes subjected to oxygen and glucose deprivationBożena GabryelSebastian LiberMetformin, a type 2 anti-diabetic drug and an activator of AMP-activated protein kinase (AMPK), has been shown to reduce infarct size and pathological changes affecting astroglia in animal models of ischemic stroke. In this study, we evaluated how metformin affects cell viability, apoptosis and determined the role of AMPK, as well as JNK p46/p54 and p38 kinases, in the observed phenomena in the culture of primary rat cortical astrocytes subjected to 12 h of oxygen and glucose deprivation (OGD). Metformin improved cell viability, reduced the fraction of apoptotic nuclei, and inhibited the activation of the executive caspase-3. Decreased activation of JNK p54 and p38 was associated with increased Bcl-XL expression and decreased mitochondrial leakage of cytochrome c. However, only cell viability and partially the fraction of apoptotic nuclei varied concomitantly with changes in AMPK activity, suggesting that AMPK is critical for metformin-mediated effects and regulates programmed cell death in a caspase-independent manner. Experiments with the inhibitors of JNK and p38 supports the role of these kinases in the drug-related inhibition of mitochondrial and extrinsic pathway of apoptosis.https://www.termedia.pl/Metformin-limits-apoptosis-in-primary-rat-cortical-astrocytes-subjected-to-oxygen-and-glucose-deprivation,20,34468,1,1.htmlmetformin apoptosis astrocytes oxygen-glucose deprivation |
| spellingShingle | Bożena Gabryel Sebastian Liber Metformin limits apoptosis in primary rat cortical astrocytes subjected to oxygen and glucose deprivation Folia Neuropathologica metformin apoptosis astrocytes oxygen-glucose deprivation |
| title | Metformin limits apoptosis in primary rat cortical astrocytes subjected to oxygen and glucose deprivation |
| title_full | Metformin limits apoptosis in primary rat cortical astrocytes subjected to oxygen and glucose deprivation |
| title_fullStr | Metformin limits apoptosis in primary rat cortical astrocytes subjected to oxygen and glucose deprivation |
| title_full_unstemmed | Metformin limits apoptosis in primary rat cortical astrocytes subjected to oxygen and glucose deprivation |
| title_short | Metformin limits apoptosis in primary rat cortical astrocytes subjected to oxygen and glucose deprivation |
| title_sort | metformin limits apoptosis in primary rat cortical astrocytes subjected to oxygen and glucose deprivation |
| topic | metformin apoptosis astrocytes oxygen-glucose deprivation |
| url | https://www.termedia.pl/Metformin-limits-apoptosis-in-primary-rat-cortical-astrocytes-subjected-to-oxygen-and-glucose-deprivation,20,34468,1,1.html |
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