ERK activation induced by selenium treatment significantly downregulates beta/gamma-secretase activity and Tau phosphorylation in the transgenic rat overexpressing human selenoprotein M.

Abstract:

:Selenium reportedly contribute to the modulation process of protein phosphorylation to regulate various cellular functions including growth, differentiation, proliferation and development. The aim of this study was to investigate whether selenium and Selenoprotein M (SelM) affects the mechanism of Alzheimer's disease. To achieve this, we determined the change of the MAPK pathway, secretase activity, and Tau phosphorylation in the transgenic rat overexpressing human selenoprotein M. Based on these results, we concluded that, i) CMV/GFP-hSelM Tg rats showed a high activity level of antioxidant enzyme in the brain tissues, ii) in response to selenium treatment, the ERK signaling pathway was significantly increased in Tg rats, but did not change in wild-type rats, iii) the activation of the ERK pathway by selenium treatment and SelM overexpression induced the inhibition of the alpha/gamma-secretase activity related to the protection of Abeta-42 production, iv) the activation of the ERK pathway by selenium treatment and SelM overexpression inhibited the phosphorylation in several sites of Tau protein. Therefore, these results provide strong evidence that selenium treatment and SelM activate the ERK pathway to attenuate alpha/gamma-secretase-mediated proteolysis and Tau phosphorylation to protect brain function.

journal_name

Int J Mol Med

authors

Yim SY,Chae KR,Shim SB,Hong JT,Park JY,Lee CY,Son HJ,Sheen YY,Hwang DY

doi

10.3892/ijmm_00000211

subject

Has Abstract

pub_date

2009-07-01 00:00:00

pages

91-6

issue

1

eissn

1107-3756

issn

1791-244X

journal_volume

24

pub_type

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