ERK activation induced by selenium treatment significantly downregulates beta/gamma-secretase activity and Tau phosphorylation in the transgenic rat overexpressing human selenoprotein M.
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.
Yim
Su Y
SY
Department of Laboratory Animal Resources, National Institute of Toxicological Research, Korea FDA, Seoul 122-704, Korea.
Chae
Kab R
KR
Shim
Sun B
SB
Hong
Jin T
JT
Park
Jung Y
JY
Lee
Chung Y
CY
Son
Hong J
HJ
Sheen
Yhun Y
YY
Hwang
Dae Y
DY
D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D000818:Animals; D015536:Down-Regulation; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation; D051381:Rats; D055647:Rats, Transgenic; D051140:Selenoproteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D018038:Sodium Selenite / Q000494:pharmacology*; D016875:tau Proteins / Q000378:metabolism*
C448999:SELM protein, human; D051140:Selenoproteins; D016875:tau Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D053829:Amyloid Precursor Protein Secretases; D018038:Sodium Selenite