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
[11]   Protocols to detect senescence-associated beta-galactosidase (SA-βgal) activity, a biomarker of senescent cells in culture and in vivo [J].
Debacq-Chainiaux, Florence ;
Erusalimsky, Jorge D. ;
Campisi, Judith ;
Toussaint, Olivier .
NATURE PROTOCOLS, 2009, 4 (12) :1798-1806
[12]   Increased IGF mRNA in human skeletal muscle after creatine supplementation [J].
Deldicque, L ;
Louis, M ;
Theisen, D ;
Nielens, H ;
Dehoux, M ;
Thissen, JP ;
Rennie, MJ ;
Francaux, M .
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE, 2005, 37 (05) :731-736
[13]   Boosting the Photoaged Skin: The Potential Role of Dietary Components [J].
Geng, Ruixuan ;
Kang, Seong-Gook ;
Huang, Kunlun ;
Tong, Tao .
NUTRIENTS, 2021, 13 (05)
[14]   Age and insulin-like growth factor-1 impact PCNA monoubiquitination in UVB-irradiated human skin [J].
Hutcherson, Rebekah J. ;
Gabbard, Ryan D. ;
Castellanos, Amber J. ;
Travers, Jeffrey B. ;
Kemp, Michael G. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2021, 296
[15]   Impact of Age and Insulin-Like Growth Factor-1 on DNA Damage Responses in UV-Irradiated Human Skin [J].
Kemp, Michael G. ;
Spandau, Dan F. ;
Travers, Jeffrey B. .
MOLECULES, 2017, 22 (03)
[16]   Insulin-like Growth Factor 1 Receptor Signaling Is Required for Optimal ATR-CHK1 Kinase Signaling in Ultraviolet B (UVB)-irradiated Human Keratinocytes [J].
Kemp, Michael G. ;
Spandau, Dan F. ;
Simman, Richard ;
Travers, Jeffrey B. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2017, 292 (04) :1231-1239
[17]  
Kreider Richard B., 2011, Physical Activity and Nutrition, V15, P53
[18]   Nicotinamide Exerts Antioxidative Effects on Senescent Cells [J].
Kwak, Ju Yeon ;
Ham, Hyun Joo ;
Kim, Cheol Min ;
Hwang, Eun Seong .
MOLECULES AND CELLS, 2015, 38 (03) :229-235
[19]   The effect of aging in primary human dermal fibroblasts [J].
Lago, Juliana Carvalhaes ;
Puzzi, Maria Beatriz .
PLOS ONE, 2019, 14 (07)
[20]   Senescence-associated β-galactosidase is lysosomal β-galactosidase [J].
Lee, BY ;
Han, JA ;
Im, JS ;
Morrone, A ;
Johung, K ;
Goodwin, EC ;
Kleijer, WJ ;
DiMaio, D ;
Hwang, ES .
AGING CELL, 2006, 5 (02) :187-195