γ-Tocotrienol prevents cell cycle arrest in aged human fibroblast cells through p16INK4a pathway

Zainuddin, Azalina; Chua, Kien Hui; Tan, Jen Kit; Jaafar, Faizul; Makpol, Suzana

doi:10.1007/s13105-016-0524-2

Cited by 10 publications

(10 citation statements)

References 39 publications

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“…In this study, Hsp70 was upregulated in γT3-treated senescent cells compared with vehicle-treated senescent cells. Our results suggest that γT3 may increase the stress response of senescent cells which accounts for its pro-survival effect on senescent cells as observed in previous study [ 15 ]. Cells isolated from aged organisms or undergoing replicative senescence have reduced heat shock response.…”

Section: Resultssupporting

confidence: 85%

“…Written consents were obtained from their parents with Ethical approval code: FF-249-2012. The isolation, culture and passaging of HDFs were performed as described previously [ 15 ]. Briefly, epidermis of the skin was removed.…”

Section: Methodsmentioning

confidence: 99%

“…Transcriptomic analysis reveals that γT3 modulates expressions of genes involved in inflammation, apoptosis, protein transport and cell redox [ 14 ]. γT3 decreases protein expressions of p16 INK4a , cyclin D1 and hypo-phosphorylated retinoblastoma (pRb) in senescent HDFs [ 15 ]. Although the pro-survival effect of γT3 on senescent HDFs has been reported, the global proteomic profile of senescent HDFs treated with γT3 remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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

Tan

Jaafar

Makpol

2018

BMC Complement Altern Med

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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.

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Section: Resultssupporting

confidence: 85%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Tan

Jaafar

Makpol

2018

BMC Complement Altern Med

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“…Previous studies have shown that TRF treatment of senescent fibroblast cells increased the expression of telomerase and enhanced the elongation of telomere [ 26 ]. Furthermore, γ-tocotrienol treatment of senescent cells downregulates p16, cyclin D1 and hypophosphorylated-Rb, all of which are involved in cell cycle arrest [ 32 ]. Thus, TRF is postulated to modulate telomerase expression, increase the expression of proteins involved in cell cycle to prevent cell cycle arrest and promote proliferation of myoblasts.…”

Section: Discussionmentioning

confidence: 99%

Targeting myomiRs by tocotrienol-rich fraction to promote myoblast differentiation

et al. 2018

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BackgroundSeveral muscle-specific microRNAs (myomiRs) are differentially expressed during cellular senescence. However, the role of dietary compounds on myomiRs remains elusive. This study aimed to elucidate the modulatory role of tocotrienol-rich fraction (TRF) on myomiRs and myogenic genes during differentiation of human myoblasts. Young and senescent human skeletal muscle myoblasts (HSMM) were treated with 50 μg/mL TRF for 24 h before and after inducing differentiation.ResultsThe fusion index and myotube surface area were higher (p < 0.05) on days 3 and 5 than that on day 1 of differentiation. Ageing reduced the differentiation rate, as observed by a decrease in both fusion index and myotube surface area in senescent cells (p < 0.05). Treatment with TRF significantly increased differentiation at days 1, 3 and 5 of young and senescent myoblasts. In senescent myoblasts, TRF increased the expression of miR-206 and miR-486 and decreased PTEN and PAX7 expression. However, the expression of IGF1R was upregulated during early differentiation and decreased at late differentiation when treated with TRF. In young myoblasts, TRF promoted differentiation by modulating the expression of miR-206, which resulted in the reduction of PAX7 expression and upregulation of IGF1R.ConclusionTRF can potentially promote myoblast differentiation by modulating the expression of myomiRs, which regulate the expression of myogenic genes.

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“…In previous studies, Zainuddin et al found overexpression of P16 (INK4a) mRNA in human diploid broblasts [18]. Hypertrophic LF hyperplasia is caused by excessive proliferation of broblasts and imbalance of elastic/collagen ber ratio [19].…”

Section: Discussionmentioning

confidence: 97%

The correlation between imaging expression of P16 and S100 in hypertrophic ligamentum flavum

Liu

Kan

et al. 2020

Preprint

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Background: Lumbar spinal stenosis (LSS) is a common degenerative disease, which can lead to neurological dysfunction and requires surgical treatment. In the previous study, we used H&E staining and immunohistochemistry to qualitatively analyze the expression of S100 and P16 in the pathological process of ligamentum flavum (LF) hypertrophy in patients with LSS. To further explore the relationship between P16, S100 and LF hypertrophy in patients with LSS, we quantitatively detected S100 and P16 and their expressed products based on molecular biology techniques, and analyzed their imaging correlation.Methods: Before posterior lumbar surgery, LF thickness was measured by Magnetic Resonance Imaging (MRI). Through the operation, we obtained the specimens of LF from 120 patients, all of whom were L4/5 LF. They were designated: simple lumbar disc herniation (LDH), single-segment spinal stenosis (SLSS), and double-segment LSS (DLSS). The detection of each side of LF was assessed. S100 and P16 and their expression products were detected by western blot and quantitative polymerase chain reaction (qPCR).Results: The dorsal mRNA expression of P16 in DLSS group was significantly higher than that in SLSS group. On the dorsal and dural side of LF, the expression of P16 mRNA and proteins in the LDH group was significantly lower than that in SLSS and DLSS groups. We found a correlation between the thickness of LF and the expression of P16. However, there was no significant difference in the expression of S100 mRNA and S100 protein on both sides of the ligament and among the three groups, and no significant correlation between the expression of S100 and the thickness of LF.Conclusions: P16 is involved in the process of LF hypertrophy in patients with LSS, and the imaging thickness of LF is related to the expression of P16. No obvious evidence proves that S100 may be related to the hypertrophy of LF in patients with LSS.

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γ-Tocotrienol prevents cell cycle arrest in aged human fibroblast cells through p16INK4a pathway

Cited by 10 publications

References 39 publications

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

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

Targeting myomiRs by tocotrienol-rich fraction to promote myoblast differentiation

The correlation between imaging expression of P16 and S100 in hypertrophic ligamentum flavum

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