Hexapeptide-11 is a novel modulator of the proteostasis network in human diploid fibroblasts
Despite the fact that several natural products (e.g. crude extracts or purified compounds) have been found to activate cell antioxidant responses and/or delay cellular senescence the effect(s) of small peptides on cell viability and/or modulation of protective mechanisms (e.g. the proteostasis netwo...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-08-01
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| Series: | Redox Biology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231715000415 |
| _version_ | 1818445015314071552 |
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| author | Aimilia D. Sklirou Marianna Ralli Maria Dominguez Issidora Papassideri Alexios-Leandros Skaltsounis Ioannis P. Trougakos |
| author_facet | Aimilia D. Sklirou Marianna Ralli Maria Dominguez Issidora Papassideri Alexios-Leandros Skaltsounis Ioannis P. Trougakos |
| author_sort | Aimilia D. Sklirou |
| collection | DOAJ |
| description | Despite the fact that several natural products (e.g. crude extracts or purified compounds) have been found to activate cell antioxidant responses and/or delay cellular senescence the effect(s) of small peptides on cell viability and/or modulation of protective mechanisms (e.g. the proteostasis network) remain largely elusive. We have thus studied a hexapeptide (Hexapeptide-11) of structure Phe–Val–Ala–Pro–Phe–Pro (FVAPFP) originally isolated from yeast extracts and later synthesized by solid state synthesis to high purity. We show herein that Hexapeptide-11 exhibits no significant toxicity in normal human diploid lung or skin fibroblasts. Exposure of fibroblasts to Hexapeptide-11 promoted dose and time-dependent activation of proteasome, autophagy, chaperones and antioxidant responses related genes. Moreover, it promoted increased nuclear accumulation of Nrf2; higher expression levels of proteasomal protein subunits and increased proteasome peptidase activities. In line with these findings we noted that Hexapeptide-11 conferred significant protection in fibroblasts against oxidative-stress-mediated premature cellular senescence, while at in vivo skin deformation assays in human subjects it improved skin elasticity. Finally, Hexapeptide-11 was found to induce the activity of extracellular MMPs and it also suppressed cell migration. Our presented findings indicate that Hexapeptide-11 is a promising anti-ageing agent. Keywords: Hexapeptide-11, Human fibroblasts, Proteasome, Proteostasis, Senescence, Chaperone, Antioxidant responses |
| first_indexed | 2024-12-14T19:25:06Z |
| format | Article |
| id | doaj.art-85c7aa085b8d4bd88278763fa2cf906c |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-14T19:25:06Z |
| publishDate | 2015-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-85c7aa085b8d4bd88278763fa2cf906c2022-12-21T22:50:12ZengElsevierRedox Biology2213-23172015-08-015205215Hexapeptide-11 is a novel modulator of the proteostasis network in human diploid fibroblastsAimilia D. Sklirou0Marianna Ralli1Maria Dominguez2Issidora Papassideri3Alexios-Leandros Skaltsounis4Ioannis P. Trougakos5Department of Cell Biology and Biophysics, Faculty of Biology, University of Athens, Panepistimiopolis, Athens 15784, GreeceKorres S.A. Natural Products, 57th Athens-Lamia National Road, 32011 Inofyta, GreeceLonza, 70 Tyler Place, South Plainfield, NJ 07080, USADepartment of Cell Biology and Biophysics, Faculty of Biology, University of Athens, Panepistimiopolis, Athens 15784, GreeceDepartment of Pharmacognosy and Natural Products Chemistry, Faculty of Pharmacy, University of Athens, Panepistimiopolis Zografou, 15771 Athens, GreeceDepartment of Cell Biology and Biophysics, Faculty of Biology, University of Athens, Panepistimiopolis, Athens 15784, Greece; Corresponding author.Despite the fact that several natural products (e.g. crude extracts or purified compounds) have been found to activate cell antioxidant responses and/or delay cellular senescence the effect(s) of small peptides on cell viability and/or modulation of protective mechanisms (e.g. the proteostasis network) remain largely elusive. We have thus studied a hexapeptide (Hexapeptide-11) of structure Phe–Val–Ala–Pro–Phe–Pro (FVAPFP) originally isolated from yeast extracts and later synthesized by solid state synthesis to high purity. We show herein that Hexapeptide-11 exhibits no significant toxicity in normal human diploid lung or skin fibroblasts. Exposure of fibroblasts to Hexapeptide-11 promoted dose and time-dependent activation of proteasome, autophagy, chaperones and antioxidant responses related genes. Moreover, it promoted increased nuclear accumulation of Nrf2; higher expression levels of proteasomal protein subunits and increased proteasome peptidase activities. In line with these findings we noted that Hexapeptide-11 conferred significant protection in fibroblasts against oxidative-stress-mediated premature cellular senescence, while at in vivo skin deformation assays in human subjects it improved skin elasticity. Finally, Hexapeptide-11 was found to induce the activity of extracellular MMPs and it also suppressed cell migration. Our presented findings indicate that Hexapeptide-11 is a promising anti-ageing agent. Keywords: Hexapeptide-11, Human fibroblasts, Proteasome, Proteostasis, Senescence, Chaperone, Antioxidant responseshttp://www.sciencedirect.com/science/article/pii/S2213231715000415 |
| spellingShingle | Aimilia D. Sklirou Marianna Ralli Maria Dominguez Issidora Papassideri Alexios-Leandros Skaltsounis Ioannis P. Trougakos Hexapeptide-11 is a novel modulator of the proteostasis network in human diploid fibroblasts Redox Biology |
| title | Hexapeptide-11 is a novel modulator of the proteostasis network in human diploid fibroblasts |
| title_full | Hexapeptide-11 is a novel modulator of the proteostasis network in human diploid fibroblasts |
| title_fullStr | Hexapeptide-11 is a novel modulator of the proteostasis network in human diploid fibroblasts |
| title_full_unstemmed | Hexapeptide-11 is a novel modulator of the proteostasis network in human diploid fibroblasts |
| title_short | Hexapeptide-11 is a novel modulator of the proteostasis network in human diploid fibroblasts |
| title_sort | hexapeptide 11 is a novel modulator of the proteostasis network in human diploid fibroblasts |
| url | http://www.sciencedirect.com/science/article/pii/S2213231715000415 |
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