Open AccessBiphasic effects of statins on neuron cell functions under oxygen–glucose deprivation and normal culturing conditions via different mechanisms
Author(s) -
Wang Hui,
Chen Yun,
Li Ping,
Chen Yan,
Yu Danfang,
Tan Qian,
Liu Xiaoli,
Guo Zhenli
Publication year - 2022
Publication title -
pharmacology research and perspectives
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.975
H-Index - 27
ISSN - 2052-1707
DOI - 10.1002/prp2.1001
Subject(s) - cerivastatin , pitavastatin , atorvastatin , lovastatin , pharmacology , neuron , statin , hmg coa reductase , medicine , inflammation , chemistry , cholesterol , reductase , pravastatin , biochemistry , enzyme , psychiatry
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.