Study summary · research use only
[KE peptide regulates SIRT1, PARP1, PARP2 gene expression and protein synthesis in human mesenchymal stem cells aging.]
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This in vitro study examined the effect of the KE peptide (Lys-Glu, also known as vilon) on SIRT1, PARP1, and PARP2 gene expression and protein synthesis during aging of human mesenchymal stem cells (MSCs), and used molecular modeling to explore how the peptide might interact with DNA sequences in the promoters of these genes. The KE peptide increased SIRT1 gene expression and protein synthesis in younger MSCs, while reducing PARP1 and PARP2 gene expression and protein synthesis during MSC aging. Molecular modeling suggested the peptide can interact with specific double-stranded DNA sequences found in the SIRT1, PARP1, and PARP2 gene promoters. The authors describe these findings as underlying the peptide's biological activity and geroprotective effect during replicative aging of human MSCs.
Abstract
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 «young» 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. Показано, что пептид KE (Lys–Glu, вилон) обладает иммуномодулирующим, онкостатическим и геропротекторным свойствами. Цель работы — оценка влияния пептида KE на экспрессию генов и синтез белков SIRT1, PARP1, PARP2 при старении мезенхимальных стволовых клеток (MSC) человека. Пептид KE повышает экспрессию гена и синтез белка SIRT1 в «молодых» MSC, соответственно, в 6 и 8,2 раза. Пептид KE снижает экспрессию гена и синтез белка PARP1 при старении MSC, соответственно, в 2,1 и 5,3 раза, а также снижает экспрессию гена и синтез белка PARP2, соответственно, в 2,1 и 4,7 раза. По данным молекулярного моделирования, пептид KE может взаимодействовать с последовательностью GCGG двунитевой ДНК (днДНК) в классической В-форме и с последовательностью GGGC искривленной днДНК нуклеосомы. В промоторах генов SIRT1, PARP1, PARP2 человека обнаружены указанные последовательности днДНК. Таким образом, пептид KE регулирует экспрессию генов и синтез белков SIRT1, PARP1, PARP2 в MSC человека при репликативном старении, что лежит в основе биологической активности и геропротекторного эффекта этого пептида.
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