Overexpression of dishevelled-1 attenuates wortmannin-induced hyperphosphorylation of cytoskeletal proteins in N2a cell.

Abstract

AIM:

To investigate the effect of dishevelled-1 (DVL-1) on wortmannin-induced Alzheimer-like hyperphosphorylation of cytoskeletal proteins in mouse neuroblastoma 2a (N2a) cells.

METHODS:

Cultured N2a cells were transitorily transfected with DVL-1 expression plasmid using Lipofectamine 2000. Western blot and immunofluorescence microscopy were used to measure the phosphorylation of neurofilament and tau.

RESULTS:

Level of phosphorylated neurofilament at SMI31 epitope and phosphorylated tau determined by PHF-1 was increased at 1 h and 3 h and back to normal at 6 h after wortmannin 1 micromol/L treatment. The highest level of phosphorylated neurofilament and phosphorylated tau was seen at 1 h and 3 h after wortmannin treatment, respectively. When DVL-1 protein was overexpressed, the hyperphosphorylation of neurofilament at SMI31 and SMI32 epitopes and tau at PHF-1 (Ser-396/404), M4 (Thr-231/Ser-235), and Tau-1 (Ser-198/199/202) epitopes was attenuated.

CONCLUSION:

Overexpression of mouse DVL-1 protein inhibits wortmannin-induced hyperphosphorylation of neurofilament and tau in N2a cells.

• Authors: Hai-hong Wang, Ai-hong Zhang, Ling-qiang Zhu, Qun Wang, Jian-zhi Wang
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 26 Issue 6 Pg. 679-84 (Jun 2005) ISSN: 1671-4083 [Print] United States
• PMID: 15916733 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Androstadienes
• Dishevelled Proteins
• Dvl1 protein, mouse
• Neurofilament Proteins
• Phosphoproteins
• Proteins
• tau Proteins
• Wortmannin

Topics

• Adaptor Proteins, Signal Transducing
• Androstadienes (pharmacology)
• Animals
• Dishevelled Proteins
• Mice
• Neuroblastoma (metabolism, pathology)
• Neurofilament Proteins (metabolism)
• Phosphoproteins
• Phosphorylation (drug effects)
• Proteins (genetics, metabolism, physiology)
• Transfection
• Tumor Cells, Cultured
• Wortmannin
• tau Proteins (metabolism)