Open AccessEffect of atorvastatin on Aβ 1–42 ‐induced alteration of SESN2, SIRT1, LC3II and TPP1 protein expressions in neuronal cell cultures
Author(s) -
Çelik Hande,
Karahan Hande,
KelicenUğur Pelin
Publication year - 2020
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1111/jphp.13208
Subject(s) - atorvastatin , autophagy , neuroprotection , autophagosome , neurotoxicity , chemistry , oxidative stress , western blot , pharmacology , microbiology and biotechnology , biochemistry , biology , apoptosis , toxicity , gene , organic chemistry
Objectives Sestrins (SESNs) and sirtuins (SIRTs) are antioxidant and antiapoptotic genes and crucial mediators for lysosomal autophagy regulation that play a pivotal role in the Alzheimer's disease (AD). Recently, statins have been linked to the reduced prevalence of AD in statin‐prescribed populations yet molecular basis for the neuroprotective action of statins is still under debate. Methods This study was undertaken whether Aβ‐induced changes of SESN2 and SIRT1 protein expression, autophagy marker LC3II and lysosomal enzyme TPP1 affected by atorvastatin (Western blot) and its possible role in Aβ neurotoxicity (ELISA). Key findings/results We showed that SESN2 and LC3II expressions were elevated, whereas SIRT1 and TPP1 expressions were decreased in the Aβ 1–42 ‐exposed human neuroblastoma cells (SH‐SY5Y). Co‐administration of atorvastatin with Aβ 1–42 compensates SESN2 increase and recovers SIRT1 decline by reducing oxidative stress, decreasing SESN2 expression and increasing SIRT1 expression by its neuroprotective action. Atorvastatin induced LC3II but not TPP1 level in the Aβ 1–42 ‐exposed cells suggested that atorvastatin is effective in the formation of autophagosome but not on the expression of the specific lysosomal enzyme TPP1. Discussion and conclusion Together, these results indicate that atorvastatin induced SESN2, SIRT1 and LC3II levels play a protective role against Aβ 1–42 neurotoxicity.