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P2‐145: Regulation of ASF‐mediated alternative splicing of tau exon 10 by PKA
Author(s) -
Shi Jianhua,
Gu Qingqing,
Wang Weihua,
Iqbal Khalid,
Grundke-Iqbal Inge,
Gong Cheng X.,
Liu Fei
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.1218
Subject(s) - rna splicing , exon , alternative splicing , hek 293 cells , phosphorylation , chemistry , tau protein , hyperphosphorylation , microbiology and biotechnology , biology , biochemistry , gene , alzheimer's disease , rna , medicine , disease
culture, HEK293/tau was treated with CA, OA alone or with the lysosome inhibitor, proteasome, or calpain inhibtor (chloroquine; MG132; calpain inhibitor III) and the level of total and hyperphosphorylated tau was detected by Western blotting. Results: 1) We observed unexpectedly that the level of endogenous tau was decreased upon inhibition of autophagic lysosomal system by 3-methyladenine or inhibition of lysosomal proteases by chloroquine in the rat brain. Injection of MG-132 with chloroquine into the rat hippocampus rescued the decease of tau. 2) In HEK293/tau cell, CA or OA treatment induced the increase of total and hyperphosphorylated tau and chloroquine reversed the increase of total and hyperphosphorylated tau. MG-132 or calpain inhibitor III treatment could counteract the effect of chloroquine. Conclusions: Endogenous tau may be not directly degraded by autophagy. Inhibition of lysosome by choloroquine may increase the activity of proteasome or calpain and then induce the degradation of tau. This work extends our understanding of the degradation pathway of tau.