| Background and Objectives:Vascular aging problem has become the new targets for the prevention and treatment of cardiovascular diseases.Vascular aging as a degenerative disease,its pathological changes mainly involve apoptosis of endothelial cells and smooth muscle cells.Vascular aging as a degenerative disease,its pathological changes mainly involved in endothelial cells and smooth muscle cell senescence and apoptosis.Research shows that the occurrence of senile diseases not only associated with the aging of cells,also has a close relation with tissue cells apoptosis,and cell apoptosis in various organizations also play an important role in aging.Study found that the stability of the chromosome and cell survival requires telomere structure and function is complete,the telomeres damage caused by abnormal telomeres shorten can lead to cell apoptosis.In turn,in the apoptosis induced by DNA damage telomere sequence is rapid,severe leakage,and telomere mass loss occurred in the early days of cell apoptosis.Theory of telomeres is currently one of the recognized mechanism of aging,the study found that telomere length shorten started the process of cell apoptosis,telomeres may through the form of apoptosis and vascular aging.When telomeres shorten due to split to critical length,the cell stops dividing to apoptosis,but the specific mechanism is unclear.Silent information adjusting factor 1(silent information regulator 1,Sirtl)is one of the members of the family of mammals move Sirtuins are dependent on nicotine amine adenine dinucleotide(NAD +)class III histone acetylation enzyme.Sirtl is important anti-aging protein,by making multiple protein acetylation and change its activity,involving intracellular gene silencing,energy metabolism,cell apoptosis and oxidative stress and so on a variety of biological functions.P53 activity in cells function mainly reflects in the block of cell cycle,promoting apoptosis and DNA repair.Recent studies have shown that SIRT1 to acetylation enzyme and closely related to cell apoptosis,SIRT1 may also by P53 protein acetylation 382th lysine residues,reduce the combination of P53 protein and DNA cis element ability,thus inhibiting apoptosis.Telomere is through the SIRT1/P53 pathway regulating apoptosis of smooth muscle cells has not been reported.This experiment was to explore different telomere oligonucleotide sequence influence on smooth muscle cell apoptosis,as well as SIRT1/P53 pathway is involved in the regulation and control.Methods:1.Three telomere repeat sequence TE-12(TTAGGG)2?TE-24(TTAGGG)4?TE-36(TTAGGG)6 transfected to A7R5 cell,and transfection efficiency was detected under the fluorescence microscope observation.2.Flow cytometry was used to test the telomeres oligonucleotide sequence A7R5 cell apoptosis after transfection.3.RT-PCR and Western blot detected TE-12?TE-24?TE-36 the control group and so on four groups of SIRT1,P53 gene and protein level.Results:1.A7R5 cell apoptosis rate caused by different telomere oligonucleotide sequence is different.TE-12 which has a single telomeres structure caused apoptosis is the most obvious,followed by the four polymers and a single structure of TE-36,and four telomere repeated sequence of TE-24 for forming a G-four dimer structure,induced apoptosis of the weakest role.2.SIRT1 participated in A7R5 cells apoptosis induced by telomere oligonucleotide sequence,but also cut the expression of P53 protein levels.After transfection of TE-12,TE-24,TE-36 three group of telomere oligonucleotide sequence,SIRT1,P53 gene and protein levels in accordance with the change trend of cell apoptosis,namely TE-12 groups of SIRT1,P53 the highest expression,and apoptosis is the most obvious.Conclusions:1.Telomere oligonucleotide sequence of different structure caused A7R5 cells apoptosis at different levels.2.In the selection of three kinds of structure,apoptosis in single sequence telomere TE-12 was the most obvious.3.The role of the telomere oligonucleotide sequence in A7R5 cell apoptosis may be associated with SIRT1/P53 signal pathway. |
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