Biphasic effects of statins on neuron cell functions under oxygen–glucose deprivation and normal culturing conditions via different mechanisms
Abstract While there is a growing interest in the use of statins, HMG‐CoA reductase inhibitors, to treat neurodegenerative diseases, statins are associated with conflicting effects within the central nervous system (CNS) without clear evidence of the underlying mechanisms. This study systematically...
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| Format: | Article |
| Language: | English |
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Wiley
2022-10-01
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| Series: | Pharmacology Research & Perspectives |
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| Online Access: | https://doi.org/10.1002/prp2.1001 |
| _version_ | 1817984739394453504 |
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| author | Hui Wang Yun Chen Ping Li Yan Chen Danfang Yu Qian Tan Xiaoli Liu Zhenli Guo |
| author_facet | Hui Wang Yun Chen Ping Li Yan Chen Danfang Yu Qian Tan Xiaoli Liu Zhenli Guo |
| author_sort | Hui Wang |
| collection | DOAJ |
| description | Abstract While there is a growing interest in the use of statins, HMG‐CoA reductase inhibitors, to treat neurodegenerative diseases, statins are associated with conflicting effects within the central nervous system (CNS) without clear evidence of the underlying mechanisms. This study systematically investigated effects of four statins (atorvastatin, pitavastatin, cerivastatin, and lovastatin) on neuronal cells under pathological condition using an in vitro model depicting ischemic injury, as well as tested under physiological condition. All four statins at micromolar concentrations display toxic effects on neuron cells under physiological condition. Atorvastatin and cerivastatin but not pitavastatin or lovastatin at nanomolar concentrations display protective effects on neuron cells under ischemic injury condition, via decreased ischemic injury‐induced oxidative stress, oxidative damage, and inflammation. Mechanistically, atorvastatin, pitavastatin, and lovastatin induces neuron cell apoptosis via prenylation‐independent manner. Other mechanisms are involved in the pro‐apoptotic effect of cerivastatin. Prenylation is not involved in the protective effects of statins under ischemic injury condition. Our work provides better understanding on the multiple differential effects of statins on neuron cells under physiological condition and ischemic injury, and elucidate their underlying mechanisms, which may be of relevance to the influence of statins in CNS. |
| first_indexed | 2024-04-13T23:48:44Z |
| format | Article |
| id | doaj.art-24e020ae988b4ce9a0f87b5749a3da4d |
| institution | Directory Open Access Journal |
| issn | 2052-1707 |
| language | English |
| last_indexed | 2024-04-13T23:48:44Z |
| publishDate | 2022-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pharmacology Research & Perspectives |
| spelling | doaj.art-24e020ae988b4ce9a0f87b5749a3da4d2022-12-22T02:24:11ZengWileyPharmacology Research & Perspectives2052-17072022-10-01105n/an/a10.1002/prp2.1001Biphasic effects of statins on neuron cell functions under oxygen–glucose deprivation and normal culturing conditions via different mechanismsHui Wang0Yun Chen1Ping Li2Yan Chen3Danfang Yu4Qian Tan5Xiaoli Liu6Zhenli Guo7Department of Neurology Hubei Provincial Hospital of Integrated Chinese and Western Medicine Wuhan ChinaDepartment of Neurology Hubei Provincial Hospital of Integrated Chinese and Western Medicine Wuhan ChinaDepartment of Neurology Hubei Provincial Hospital of Integrated Chinese and Western Medicine Wuhan ChinaDepartment of Neurology Hubei Provincial Hospital of Integrated Chinese and Western Medicine Wuhan ChinaDepartment of Neurology Hubei Provincial Hospital of Integrated Chinese and Western Medicine Wuhan ChinaDepartment of Neurology Hubei Provincial Hospital of Integrated Chinese and Western Medicine Wuhan ChinaDepartment of Neurology Hubei Provincial Hospital of Integrated Chinese and Western Medicine Wuhan ChinaDepartment of Neurology Hubei Provincial Hospital of Integrated Chinese and Western Medicine Wuhan ChinaAbstract While there is a growing interest in the use of statins, HMG‐CoA reductase inhibitors, to treat neurodegenerative diseases, statins are associated with conflicting effects within the central nervous system (CNS) without clear evidence of the underlying mechanisms. This study systematically investigated effects of four statins (atorvastatin, pitavastatin, cerivastatin, and lovastatin) on neuronal cells under pathological condition using an in vitro model depicting ischemic injury, as well as tested under physiological condition. All four statins at micromolar concentrations display toxic effects on neuron cells under physiological condition. Atorvastatin and cerivastatin but not pitavastatin or lovastatin at nanomolar concentrations display protective effects on neuron cells under ischemic injury condition, via decreased ischemic injury‐induced oxidative stress, oxidative damage, and inflammation. Mechanistically, atorvastatin, pitavastatin, and lovastatin induces neuron cell apoptosis via prenylation‐independent manner. Other mechanisms are involved in the pro‐apoptotic effect of cerivastatin. Prenylation is not involved in the protective effects of statins under ischemic injury condition. Our work provides better understanding on the multiple differential effects of statins on neuron cells under physiological condition and ischemic injury, and elucidate their underlying mechanisms, which may be of relevance to the influence of statins in CNS.https://doi.org/10.1002/prp2.1001neuron cellsOGDoxidative stressprenylationstatins |
| spellingShingle | Hui Wang Yun Chen Ping Li Yan Chen Danfang Yu Qian Tan Xiaoli Liu Zhenli Guo Biphasic effects of statins on neuron cell functions under oxygen–glucose deprivation and normal culturing conditions via different mechanisms Pharmacology Research & Perspectives neuron cells OGD oxidative stress prenylation statins |
| title | Biphasic effects of statins on neuron cell functions under oxygen–glucose deprivation and normal culturing conditions via different mechanisms |
| title_full | Biphasic effects of statins on neuron cell functions under oxygen–glucose deprivation and normal culturing conditions via different mechanisms |
| title_fullStr | Biphasic effects of statins on neuron cell functions under oxygen–glucose deprivation and normal culturing conditions via different mechanisms |
| title_full_unstemmed | Biphasic effects of statins on neuron cell functions under oxygen–glucose deprivation and normal culturing conditions via different mechanisms |
| title_short | Biphasic effects of statins on neuron cell functions under oxygen–glucose deprivation and normal culturing conditions via different mechanisms |
| title_sort | biphasic effects of statins on neuron cell functions under oxygen glucose deprivation and normal culturing conditions via different mechanisms |
| topic | neuron cells OGD oxidative stress prenylation statins |
| url | https://doi.org/10.1002/prp2.1001 |
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