RESUMO
It was shown that KE peptide (Lys-Glu, vilon) has immunomodulatory, oncostatic and geroprotective effects. The aim of this work is to evaluate the effect of the KE peptide on gene expression and protein synthesis of SIRT1, PARP1, PARP2 during aging of human mesenchymal stem cells (MSC). The KE peptide increased gene expression and synthesis of the SIRT1 protein in «young¼ MSCs by 6 and 8,2 times, respectively. The KE peptide reduced gene expression and PARP1 protein synthesis during MSC aging by 2,1 and 5,3 times, respectively; and also reduced gene expression and PARP2 protein synthesis by 2,1 and 4,7 times, respectively. According to molecular modeling data, the KE peptide can interact with the GCGG sequence of double-stranded DNA (dsDNA) in the classical B-form and with the GGGC sequence of the curved dsDNA nucleosome. The indicated dsDNA sequences were found in the promoters of the human SIRT1, PARP1, PARP2 genes. Thus, the KE peptide regulates gene expression and synthesis of SIRT1, PARP1, PARP2 proteins in human mesenchymal stem cells during replicative ageing, which underlies the biological activity and geroprotective effect of this peptide.
Assuntos
Células-Tronco Mesenquimais , Sirtuína 1 , Humanos , Poli(ADP-Ribose) Polimerase-1/genética , Poli(ADP-Ribose) Polimerase-1/metabolismo , Sirtuína 1/genética , DNA/química , DNA/metabolismo , Envelhecimento/genética , Expressão Gênica , Peptídeos/genética , Poli(ADP-Ribose) Polimerases/genéticaAssuntos
Poluentes Ocupacionais do Ar/toxicidade , Indústria Química , Animais , Feminino , Cobaias , Lubrificação , Masculino , Gravidez , Ratos , U.R.S.S.RESUMO
A 24-hour stay of the Rana temporaria tadpoles in solutions of the sodium and diethylamine salts of 2,4-dichlorophenoxyacitic acid (with 1 and 2 mg/l, respectively) significantly inhibits their metamorphosis. An addition of these salts to a solution containing thyroidin in a concentration of 1--5 mg/l hinders the action of hormone stimulating metamorphosis. The effect of the sodium salt of 2,4-dichlorophenoxyacetic acid prevents the destruction of some tadpoles by toxic concentrations of thyroidin. The above data justify referring the chloroderivatives of the phenoxyacetic acid to antagonists of the thyroid hormones.
