Proteomic profiling of senescent human diploid fibroblasts treated with gamma-tocotrienol

Abstract

BackgroundReplicative senescence of human diploid fibroblasts (HDFs) has been used as a model to study mechanisms of cellular aging. Gamma-tocotrienol (γT3) is one of the members of vitamin E family which has been shown to increase proliferation of senescent HDFs. However, the modulation of protein expressions by γT3 in senescent HDFs remains to be elucidated. Therefore, this study aimed to determine the differentially expressed proteins (DEPs) in young and senescent HDFs; and in vehicle- and γT3-treated senescent HDFs using label-free quantitative proteomics.MethodsWhole proteins were extracted and digested in-gel with trypsin. Peptides were detected by Orbitrap liquid chromatography mass spectrometry. Mass spectra were identified and quantitated by MaxQuant software. The data were further filtered and analyzed statistically using Perseus software to identify DEPs. Functional annotations of DEPs were performed using Panther Classification System.ResultsA total of 1217 proteins were identified in young and senescent cells, while 1218 proteins in vehicle- and γT3-treated senescent cells. 11 DEPs were found in young and senescent cells which included downregulation of platelet-derived growth factor (PDGF) receptor beta and upregulation of tubulin beta-2A chain protein expressions in senescent cells. 51 DEPs were identified in vehicle- and γT3-treated senescent cells which included upregulation of 70 kDa heat shock protein, triosephosphate isomerase and malate dehydrogenase protein expressions in γT3-treated senescent cells.ConclusionsPDGF signaling and cytoskeletal structure may be dysregulated in senescent HDFs. The pro-proliferative effect of γT3 on senescent HDFs may be mediated through the stimulation of cellular response to stress and carbohydrate metabolism. The expressions and roles of these proteins in relation to cellular senescence are worth further investigations. Data are available via ProteomeXchange with identifier PXD009933.Electronic supplementary materialThe online version of this article (10.1186/s12906-018-2383-6) contains supplementary material, which is available to authorized users.

An unbiased proteomics approach to identify the senescence-associated secretory phenotype of human bone marrow-derived mesenchymal stem cells

“…1). A recent report showed that RPSA proteins were one of several differentially expressed proteins in senescent human diploid fibroblasts treated with gamma-tocotrienol (member of the Vitamin E family shown to increase proliferation of senescent fibroblasts) [56] , thus supporting the identification of prominent ribosomal protein subunit nodes in our network analysis.…”

The Protective Effects of γ-Tocotrienol on Muscle Stem Cells Through Inhibiting Reactive Oxidative Stress Production

“…GT3 can selectively inhibit the PI3K/Akt pathway, Ras/Raf/Erk signal transduction, HMG-CoA reductase and transcription factor NF-κB, and participate in the regulation of various physiological activities of the body ( Ahsan et al, 2014 ). Transcriptomics analyses showed that GT3 regulates the expression of genes related to inflammation, protein transport and cellular redox ( Tan et al, 2018 ; Tang et al, 2019 ). It has the functions of inducing cell apoptosis, inhibiting colony formation, inhibiting cell survival and cell proliferation ( Prasad et al, 2016 ).…”

Effect of Antioxidants on the Fibroblast Replicative Lifespan In Vitro

“…More recently, Tan et al evidenced that platelet-derived growth factor (PDGF) signaling and cytoskeletal structure can be dysregulated in senescent HDFs. The proproliferative effect of gamma-tocotrienol on senescent HDFs may be mediated through the stimulation of cellular response to stress and carbohydrate metabolism [ 74 ].…”