N-stearoyl-l-Tyrosine inhibits the cell senescence and apoptosis induced by H2O2 in HEK293/Tau cells via the CB2 receptor.

Although considerable energy and money have been spent trying to inhibit Aβ production and its related metabolic enzyme activities, there are still no drug treatments available to cure even slow for Alzheimer's disease. Therefore, tau protein has been focused recently as the new target for the treatment of Alzheimer's disease. The transfected human embryonic kidney 293 (HEK 293) cells with or without Tau 411 plasmid were used to evaluate the effect of tau protein on cell viability. H2O2 was added to simulate microenvironment of oxidative stress (OS) during aging. N-stearoyl-l-tyrosine (Nstyr), one of the synthesized N-arachidonoylethanolamide analogues was administrated in HEK293/Tau cells during H2O2 insults. Cellular senescence and tau aberrant modification appeared after tau transfection and aggravated by H2O2 insult which detected by β-galactosidase staining analysis and western blotting analysis. The level of expression of Bcl-2 and the result of FCAS analysis indicated the appearance of cellular apoptosis. The expression of prosenescence moleculars such as p16-Rb and P53 were induced by tau transfection in HEK293 cells. Both p16-Rb and p53 senescent molecules were inhibited by Nstyr. AM251 (1 μM; an antagonist of CB1 cannabinoid receptor) or AM630 (1 μM; an antagonist of CB2 cannabinoid receptor) was used to offset the anti-senescence effects afforded by NsTyr. The anti-senescence and anti-apoptosis effect of NsTyr was completely abolished by AM630. Meanwhile, transfection of siRNACB2 was used to further confirm the above experimental results and it came out the similar results compared with AM630. Taken together, our results suggest that oxidative stress aggravates cellular senescence and apoptosis in HEK293/Tau, which can be reversed by Nstyr via CB2 receptor.