Creatine and Nicotinamide Prevent Oxidant-Induced Senescence in Human Fibroblasts

被引:11
作者
Mahajan, Avinash S. [1 ]
Arikatla, Venkata S. [1 ]
Thyagarajan, Anita [1 ]
Zhelay, Tetyana [1 ]
Sahu, Ravi P. [1 ]
Kemp, Michael G. [1 ,2 ]
Spandau, Dan F. [3 ,4 ,5 ]
Travers, Jeffrey B. [1 ,2 ]
机构
[1] Wright State Univ, Boonshoft Sch Med, Dept Pharmacol & Toxicol, Dayton Ohio, OH 45435 USA
[2] Dayton Vet Adm Med Ctr, Dayton Ohio, OH 45428 USA
[3] Indiana Univ Sch Med, Dept Dermatol & Biochem, Indianapolis, IN 46223 USA
[4] Indiana Univ Sch Med, Dept Mol Biol, Indianapolis, IN 46223 USA
[5] Richard L Roudebush Vet Adm Med Ctr, Indianapolis, IN 46202 USA
基金
美国国家卫生研究院;
关键词
fibroblast; senescence; reactive oxygen species; insulin-like growth factor-1; Cr; NAM; FACTOR-I RECEPTOR; BETA-GALACTOSIDASE; DNA-DAMAGE; SKIN; STRESS; PHENOTYPE; CELLS;
D O I
10.3390/nu13114102
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
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 (H2O2) 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 H2O2 on IGF-1 mRNA and protein expression. Our studies indicate that pretreatment with Cr or NAM protects DHF from the H2O2-induced cell senescence. Treatment with pro-energetics post-H2O2 had no effect. Moreover, these agents also inhibited reactive oxygen species generation from H2O2 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.
引用
收藏
页数:15
相关论文
共 49 条
[1]   Treatment with Modified Extracts of the Microalga Planktochlorella nurekis Attenuates the Development of Stress-Induced Senescence in Human Skin Cells [J].
Adamczyk-Grochala, Jagoda ;
Wnuk, Maciej ;
Duda, Magdalena ;
Zuczek, Janusz ;
Lewinska, Anna .
NUTRIENTS, 2020, 12 (04)
[2]   Creatine Prevents the Structural and Functional Damage to Mitochondria in Myogenic, Oxidatively Stressed C2C12 Cells and Restores Their Differentiation Capacity [J].
Barbieri, Elena ;
Guescini, Michele ;
Calcabrini, Cinzia ;
Vallorani, Luciana ;
Diaz, Anna Rita ;
Fimognari, Carmela ;
Canonico, Barbara ;
Luchetti, Francesca ;
Papa, Stefano ;
Battistelli, Michela ;
Falcieri, Elisabetta ;
Romanello, Vanina ;
Sandri, Marco ;
Stocchi, Vilberto ;
Ciacci, Caterina ;
Sestili, Piero .
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2016, 2016
[3]   Creatine supplementation normalizes mutagenesis of mitochondrial DNA as well as functional consequences [J].
Berneburg, M ;
Gremmel, T ;
Kürten, V ;
Schroeder, P ;
Hertel, I ;
von Mikecz, A ;
Wild, S ;
Chen, M ;
Declercq, L ;
Matsui, M ;
Ruzicka, T ;
Krutmann, J .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2005, 125 (02) :213-220
[4]   Cellular senescence: when bad things happen to good cells [J].
Campisi, Judith ;
di Fagagna, Fabrizio d'Adda .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2007, 8 (09) :729-740
[5]   Effectiveness of Creatine Supplementation on Aging Muscle and Bone: Focus on Falls Prevention and Inflammation [J].
Candow, Darren G. ;
Forbes, Scott C. ;
Chilibeck, Philip D. ;
Cornish, Stephen M. ;
Antonio, Jose ;
Kreider, Richard B. .
JOURNAL OF CLINICAL MEDICINE, 2019, 8 (04)
[6]   SKIN PHOTOSENSITIZING AGENTS AND THE ROLE OF REACTIVE OXYGEN SPECIES IN PHOTOAGING [J].
CARBONARE, MD ;
PATHAK, MA .
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, 1992, 14 (1-2) :105-124
[7]   Reactive oxygen species as mediators of cellular senescence [J].
Colavitti, R ;
Finkel, T .
IUBMB LIFE, 2005, 57 (4-5) :277-281
[8]   Oxidative Stress Induces Telomere Dysfunction and Senescence by Replication Fork Arrest [J].
Coluzzi, Elisa ;
Leone, Stefano ;
Sgura, Antonella .
CELLS, 2019, 8 (01)
[9]   The Senescence-Associated Secretory Phenotype: The Dark Side of Tumor Suppression [J].
Coppe, Jean -Philippe ;
Desprez, Pierre-Yves ;
Krtolica, Ana ;
Campisi, Judith .
ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE, 2010, 5 :99-118
[10]   ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases [J].
Davalli, Pierpaola ;
Mitic, Tijana ;
Caporali, Andrea ;
Lauriola, Angela ;
D'Arca, Domenico .
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2016, 2016