Changes Of PTEN In Cells In Which Experimental Alzheimer's Disease Was Induced By Okadaic Acid

Objective: With morphology of cells and tau protein hyperphosphorylation as indexes of AD(Alzheimer's Disease) development, the present study was designed to explore initially the expression of PTEN in experimental AD and its relationship with tau protein hyperphosphorylation in order to comprehend the pathogeneses of AD.Methods:â‘ . SH-SY5Y cells and NG108-15 cells were treated with OA (Okadaic acid),taking cell morphology and tau protein hyperphosphorylation as indexes, to establish two types of cell model for research on AD;â‘¡Inverted microscope was used to observe the morphology of cells;â‘¢Western Blotting was used to measure the levels of phosphorylated tau protein at site of Ser396 and PTEN;â‘£RT-PCR was used to measure the levels of PTEN mRNA in SH-SY5Y cells.Results:1. Expression of PTEN in SH-SY5Y cells in which Tau protein was induced hyperphosphorylation by okadaic acidâ‘ SH-SY5Y cells changed gradually after the treatment with 40 nmol/L OA and appeared typical morphology of AD; cells were treated with 40 nmol/L OA for various periods. The levels of phosphorylated tau at site Ser396 was increased after the exposure for 12 h and reached the maximum level after 18 h, then declined to the level below normal after 48 h, indicating that OA can induce decrease of cell viabilities and tau protein hyperphosphorylation in SH-SY5Y cells.â‘¡With treatment of SH-SY5Y cells with 40 nmol/L OA for various periods, the level of PTEN and phosphorylated tau protein were detected simultaneously. The levels of phosphorylated tau protein were the same as above; the levels of PTEN was increased after the exposure for 3 h and reached the maximum level after 6 h then decreased to the level below normal after 48 h, indicating that in the proceeding of tau protein hyperphosphorylation induced by OA in SH-SH5Y cells, the expression of PTEN was altered.â‘¢With treatment of SH-SY5Y cells with 40 nmol/L OA for various periods, the levels of PTEN mRNA was increased after the exposure for 12 h and reached the maximum level after 18 h. 2. Expression of PTEN in NG108-15 cells in which Tau protein was induced hyperphosphorylation by okadaic acidâ‘ NG108-15 cells changed gradually after the treatment with 20 nmol/L OA and appeared typical morphology of AD; cells were treated with 20 nmol/L OA for various periods. The levels of phosphorylated tau at site Ser396 was increased after exposure of 6 h and reached the maximum level after 18 h, indicating that OA can induce decrease of cell viabilities and tau protein hyperphosphorylation in NG108-15 cells.â‘¡With treatment of NG108-15 cells with 20 nmol/L OA for various periods, the level of PTEN and phosphorylated tau protein were detected at the same time. The levels of phosphorylated tau protein were the same as above; the levels of PTEN was increased after exposure of 12 h and reached the maximum level after 18 h, indicating that in the proceeding of tau protein hyperphosphorylation induced by OA in NG108-15 cells, the expression of PTEN was increased.Conclusion:1. OA can induce tau protein hyperphosphorylation in SH-SY5Y cells and NG108-15 cells, and these cell models can be used on AD research. 2. In the proceeding of tau protein hyperphosphorylation induced by OA, the expression of PTEN was altered; indicating PTEN may contribute to the pathogenesis of AD.