Abstract:
:The aim of this work was to compare protective and anti-apoptotic effects of α-tocopherol at nanomolar and micromolar concentrations against 0.2 mM H(2)O(2)-induced toxicity in the PC12 neuronal cell line and to reveal protein kinases that contribute to α-tocopherol protective action. The protection by 100 nM α-tocopherol against H(2)O(2)-induced PC12 cell death was pronounced if the time of pre-incubation with α-tocopherol was 3-18 h. For the first time, the protective effect of α-tocopherol was shown to depend on its concentration in the nanomolar range (1 nM < 10 nM < 100 nM), if the pre-incubation time was 18 h. Nanomolar and micromolar α-tocopherol decreased the number of PC12 cells in late apoptosis induced by H(2)O(2) to the same extent if pre-incubation time was 18 h. Immunoblotting data showed that α-tocopherol markedly diminished the time of maximal activation of extracellular signal-regulated kinase 1/2 (ERK 1/2) and protein kinase B (Akt)-induced in PC12 cells by H(2)O(2). Inhibitors of MEK 1/2, PI 3-kinase and protein kinase C (PKC) diminished the protective effect of α-tocopherol against H(2)O(2)-initiated toxicity if the pre-incubation time was long. The modulation of ERK 1/2, Akt and PKC activities appears to participate in the protection by α-tocopherol against H(2)O(2)-induced death of PC12 cells. The data obtained suggest that inhibition by α-tocopherol in late stage ERK 1/2 and Akt activation induced by H(2)O(2) in PC12 cells makes contribution to its protective effect, while total inhibition of these enzymes is not protective.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Zakharova IO,Sokolova TV,Bayunova LV,Vlasova YA,Rychkova MP,Avrova NFdoi
10.3390/ijms130911543subject
Has Abstractpub_date
2012-01-01 00:00:00pages
11543-68issue
9issn
1422-0067pii
ijms-13-11543journal_volume
13pub_type
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