Creatine and Nicotinamide Prevent Oxidant-Induced Senescence in Human Fibroblasts

Dermal fibroblasts provide structural support by producing collagen and other structural/support proteins beneath the epidermis. Fibroblasts also produce insulin-like growth factor-1 (IGF-1), which binds to the IGF-1 receptors (IGF-1Rs) on keratinocytes to activate signaling pathways that regulate c...

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Autores principales:	Avinash S. Mahajan, Venkata S. Arikatla, Anita Thyagarajan, Tetyana Zhelay, Ravi P. Sahu, Michael G. Kemp, Dan F Spandau, Jeffrey B. Travers
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	fibroblast senescence reactive oxygen species insulin-like growth factor-1 Cr NAM Nutrition. Foods and food supply TX341-641
Acceso en línea:	https://doaj.org/article/0a728be118784672a4acf86c8ef263d8
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spelling	oai:doaj.org-article:0a728be118784672a4acf86c8ef263d82021-11-25T18:36:47ZCreatine and Nicotinamide Prevent Oxidant-Induced Senescence in Human Fibroblasts10.3390/nu131141022072-6643https://doaj.org/article/0a728be118784672a4acf86c8ef263d82021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6643/13/11/4102https://doaj.org/toc/2072-6643Dermal fibroblasts provide structural support by producing collagen and other structural/support proteins beneath the epidermis. Fibroblasts also produce insulin-like growth factor-1 (IGF-1), which binds to the IGF-1 receptors (IGF-1Rs) on keratinocytes to activate signaling pathways that regulate cell proliferation and cellular responses to genotoxic stressors like ultraviolet B radiation. Our group has determined that the lack of IGF-1 expression due to fibroblast senescence in the dermis of geriatric individuals is correlated with an increased incidence of skin cancer. The present studies tested the hypothesis that pro-energetics creatine monohydrate (Cr) and nicotinamide (NAM) can protect normal dermal human fibroblasts (DHF) against experimentally induced senescence. To that end, we used an experimental model of senescence in which primary DHF are treated with hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) in vitro, with senescence measured by staining for beta-galactosidase activity, p21 protein expression, and senescence associated secretory phenotype cytokine mRNA levels. We also determined the effect of H<sub>2</sub>O<sub>2</sub> on IGF-1 mRNA and protein expression. Our studies indicate that pretreatment with Cr or NAM protects DHF from the H<sub>2</sub>O<sub>2</sub>-induced cell senescence. Treatment with pro-energetics post-H<sub>2</sub>O<sub>2</sub> had no effect. Moreover, these agents also inhibited reactive oxygen species generation from H<sub>2</sub>O<sub>2</sub> treatment. These studies suggest a potential strategy for protecting fibroblasts in geriatric skin from undergoing stress-induced senescence, which may maintain IGF-1 levels and therefore limit carcinogenesis in epidermal keratinocytes.Avinash S. MahajanVenkata S. ArikatlaAnita ThyagarajanTetyana ZhelayRavi P. SahuMichael G. KempDan F SpandauJeffrey B. TraversMDPI AGarticlefibroblastsenescencereactive oxygen speciesinsulin-like growth factor-1CrNAMNutrition. Foods and food supplyTX341-641ENNutrients, Vol 13, Iss 4102, p 4102 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	fibroblast senescence reactive oxygen species insulin-like growth factor-1 Cr NAM Nutrition. Foods and food supply TX341-641
spellingShingle	fibroblast senescence reactive oxygen species insulin-like growth factor-1 Cr NAM Nutrition. Foods and food supply TX341-641 Avinash S. Mahajan Venkata S. Arikatla Anita Thyagarajan Tetyana Zhelay Ravi P. Sahu Michael G. Kemp Dan F Spandau Jeffrey B. Travers Creatine and Nicotinamide Prevent Oxidant-Induced Senescence in Human Fibroblasts
description	Dermal fibroblasts provide structural support by producing collagen and other structural/support proteins beneath the epidermis. Fibroblasts also produce insulin-like growth factor-1 (IGF-1), which binds to the IGF-1 receptors (IGF-1Rs) on keratinocytes to activate signaling pathways that regulate cell proliferation and cellular responses to genotoxic stressors like ultraviolet B radiation. Our group has determined that the lack of IGF-1 expression due to fibroblast senescence in the dermis of geriatric individuals is correlated with an increased incidence of skin cancer. The present studies tested the hypothesis that pro-energetics creatine monohydrate (Cr) and nicotinamide (NAM) can protect normal dermal human fibroblasts (DHF) against experimentally induced senescence. To that end, we used an experimental model of senescence in which primary DHF are treated with hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) in vitro, with senescence measured by staining for beta-galactosidase activity, p21 protein expression, and senescence associated secretory phenotype cytokine mRNA levels. We also determined the effect of H<sub>2</sub>O<sub>2</sub> on IGF-1 mRNA and protein expression. Our studies indicate that pretreatment with Cr or NAM protects DHF from the H<sub>2</sub>O<sub>2</sub>-induced cell senescence. Treatment with pro-energetics post-H<sub>2</sub>O<sub>2</sub> had no effect. Moreover, these agents also inhibited reactive oxygen species generation from H<sub>2</sub>O<sub>2</sub> treatment. These studies suggest a potential strategy for protecting fibroblasts in geriatric skin from undergoing stress-induced senescence, which may maintain IGF-1 levels and therefore limit carcinogenesis in epidermal keratinocytes.
format	article
author	Avinash S. Mahajan Venkata S. Arikatla Anita Thyagarajan Tetyana Zhelay Ravi P. Sahu Michael G. Kemp Dan F Spandau Jeffrey B. Travers
author_facet	Avinash S. Mahajan Venkata S. Arikatla Anita Thyagarajan Tetyana Zhelay Ravi P. Sahu Michael G. Kemp Dan F Spandau Jeffrey B. Travers
author_sort	Avinash S. Mahajan
title	Creatine and Nicotinamide Prevent Oxidant-Induced Senescence in Human Fibroblasts
title_short	Creatine and Nicotinamide Prevent Oxidant-Induced Senescence in Human Fibroblasts
title_full	Creatine and Nicotinamide Prevent Oxidant-Induced Senescence in Human Fibroblasts
title_fullStr	Creatine and Nicotinamide Prevent Oxidant-Induced Senescence in Human Fibroblasts
title_full_unstemmed	Creatine and Nicotinamide Prevent Oxidant-Induced Senescence in Human Fibroblasts
title_sort	creatine and nicotinamide prevent oxidant-induced senescence in human fibroblasts
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/0a728be118784672a4acf86c8ef263d8
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Creatine and Nicotinamide Prevent Oxidant-Induced Senescence in Human Fibroblasts

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