کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2052823 | 1074241 | 2006 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: The involvement of glycogen synthase kinase-3 and protein phosphatase-2A in lactacystin-induced tau accumulation The involvement of glycogen synthase kinase-3 and protein phosphatase-2A in lactacystin-induced tau accumulation](/preview/png/2052823.png)
Here, we demonstrated that lactacystin inhibited proteasome dose-dependently in HEK293 cells stably expressing tau. Simultaneously, it induces accumulation of both non-phosphorylated and hyperphosphorylated tau and decreases the binding of tau to the taxol-stabilized microtubules. Lactacystin activates glycogen synthase kinsase-3 (GSK-3) and decreases the phosphorylation of GSK-3 at serine-9. LiCl inhibits GSK-3 and thus reverses the lactacystin-induced accumulation of the phosphorylated tau. Lactacystin also inhibits protein phosphase-2A (PP-2A) and it significantly increases the level of inhibitor 1 of PP-2A. These results suggest that inhibition of proteasome by lactacystin induces tau accumulation and activation of GSK-3 and inhibition of PP-2A are involved.
Journal: FEBS Letters - Volume 580, Issue 10, 1 May 2006, Pages 2503–2511