The Effect of the Classical TSPO Ligand PK 11195 on In Vitro Cobalt Chloride Model of Hypoxia-like Condition in Lung and Brain Cell Lines
The mitochondrial translocator protein (TSPO) is a modulator of the apoptotic pathway involving reactive oxygen species (ROS) generation, mitochondrial membrane potential (Δψm) collapse, activation of caspases, and eventually initiation of the apoptotic process. In this in vitro study, H1299 lung ce...
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MDPI AG
2022-09-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/10/1397 |
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| author | Rula Amara Nidal Zeineh Sheelu Monga Abraham Weizman Moshe Gavish |
| author_facet | Rula Amara Nidal Zeineh Sheelu Monga Abraham Weizman Moshe Gavish |
| author_sort | Rula Amara |
| collection | DOAJ |
| description | The mitochondrial translocator protein (TSPO) is a modulator of the apoptotic pathway involving reactive oxygen species (ROS) generation, mitochondrial membrane potential (Δψm) collapse, activation of caspases, and eventually initiation of the apoptotic process. In this in vitro study, H1299 lung cells and BV-2 microglial cells were exposed to the hypoxia-like effect of CoCl<sub>2</sub> with or without PK 11195. Exposing the H1299 cells to 0.5 mM CoCl<sub>2</sub> for 24 h resulted in decreases in cell viability (63%, <i>p</i> < 0.05), elevation of cardiolipin peroxidation levels (38%, <i>p</i> < 0.05), mitochondrial membrane potential depolarization (13%, <i>p</i> < 0.001), and apoptotic cell death (117%, <i>p</i> < 0.05). Pretreatment with PK 11195 (25 µM) exhibited significant protective capacity on CoCl<sub>2</sub>-induced alterations in the mentioned processes. Exposure of BV-2 cells to increasing concentrations of CoCl<sub>2</sub> (0.3, 0.5, 0.7 mM) for 4 h resulted in alterations in the same cellular processes. These alterations were obtained in a dose-dependent manner, except the changes in caspases 3 and 9. The novel ligands as well as PK 1195 attenuated the in vitro hypoxia-like effects of CoCl<sub>2</sub>. It appears that the TSPO ligand PK 11195 can prevent CoCl<sub>2</sub>-induced cellular damage in both non-neuronal and brain cell lines, and they may offer a novel approach to the treatment of hypoxia-related lung and brain diseases in some cases that fail to respond to conventional therapies. |
| first_indexed | 2024-03-09T20:37:02Z |
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| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T20:37:02Z |
| publishDate | 2022-09-01 |
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| series | Biomolecules |
| spelling | doaj.art-7d72dd8249154791896eff5310f74ac92023-11-23T23:07:59ZengMDPI AGBiomolecules2218-273X2022-09-011210139710.3390/biom12101397The Effect of the Classical TSPO Ligand PK 11195 on In Vitro Cobalt Chloride Model of Hypoxia-like Condition in Lung and Brain Cell LinesRula Amara0Nidal Zeineh1Sheelu Monga2Abraham Weizman3Moshe Gavish4Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, IsraelRuth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, IsraelRuth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, IsraelSackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, IsraelRuth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, IsraelThe mitochondrial translocator protein (TSPO) is a modulator of the apoptotic pathway involving reactive oxygen species (ROS) generation, mitochondrial membrane potential (Δψm) collapse, activation of caspases, and eventually initiation of the apoptotic process. In this in vitro study, H1299 lung cells and BV-2 microglial cells were exposed to the hypoxia-like effect of CoCl<sub>2</sub> with or without PK 11195. Exposing the H1299 cells to 0.5 mM CoCl<sub>2</sub> for 24 h resulted in decreases in cell viability (63%, <i>p</i> < 0.05), elevation of cardiolipin peroxidation levels (38%, <i>p</i> < 0.05), mitochondrial membrane potential depolarization (13%, <i>p</i> < 0.001), and apoptotic cell death (117%, <i>p</i> < 0.05). Pretreatment with PK 11195 (25 µM) exhibited significant protective capacity on CoCl<sub>2</sub>-induced alterations in the mentioned processes. Exposure of BV-2 cells to increasing concentrations of CoCl<sub>2</sub> (0.3, 0.5, 0.7 mM) for 4 h resulted in alterations in the same cellular processes. These alterations were obtained in a dose-dependent manner, except the changes in caspases 3 and 9. The novel ligands as well as PK 1195 attenuated the in vitro hypoxia-like effects of CoCl<sub>2</sub>. It appears that the TSPO ligand PK 11195 can prevent CoCl<sub>2</sub>-induced cellular damage in both non-neuronal and brain cell lines, and they may offer a novel approach to the treatment of hypoxia-related lung and brain diseases in some cases that fail to respond to conventional therapies.https://www.mdpi.com/2218-273X/12/10/1397hypoxia-like conditionH1299BV-2CoCl<sub>2</sub>PK 11195 |
| spellingShingle | Rula Amara Nidal Zeineh Sheelu Monga Abraham Weizman Moshe Gavish The Effect of the Classical TSPO Ligand PK 11195 on In Vitro Cobalt Chloride Model of Hypoxia-like Condition in Lung and Brain Cell Lines Biomolecules hypoxia-like condition H1299 BV-2 CoCl<sub>2</sub> PK 11195 |
| title | The Effect of the Classical TSPO Ligand PK 11195 on In Vitro Cobalt Chloride Model of Hypoxia-like Condition in Lung and Brain Cell Lines |
| title_full | The Effect of the Classical TSPO Ligand PK 11195 on In Vitro Cobalt Chloride Model of Hypoxia-like Condition in Lung and Brain Cell Lines |
| title_fullStr | The Effect of the Classical TSPO Ligand PK 11195 on In Vitro Cobalt Chloride Model of Hypoxia-like Condition in Lung and Brain Cell Lines |
| title_full_unstemmed | The Effect of the Classical TSPO Ligand PK 11195 on In Vitro Cobalt Chloride Model of Hypoxia-like Condition in Lung and Brain Cell Lines |
| title_short | The Effect of the Classical TSPO Ligand PK 11195 on In Vitro Cobalt Chloride Model of Hypoxia-like Condition in Lung and Brain Cell Lines |
| title_sort | effect of the classical tspo ligand pk 11195 on in vitro cobalt chloride model of hypoxia like condition in lung and brain cell lines |
| topic | hypoxia-like condition H1299 BV-2 CoCl<sub>2</sub> PK 11195 |
| url | https://www.mdpi.com/2218-273X/12/10/1397 |
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