Creatine and Nicotinamide Prevent Oxidant-Induced Senescence in Human Fibroblasts.
Creatine and Nicotinamide Prevent Oxidant-Induced Senescence in Human Fibroblasts.
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DOI：
10.3390/nu13114102
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发表时间：
2021-11-16
期刊：
影响因子：
5.9
通讯作者：
Travers JB
中科院分区：
文献类型：
--
作者：
Mahajan AS;Arikatla VS;Thyagarajan A;Zhelay T;Sahu RP;Kemp MG;Spandau DF;Travers JB
真皮成纤维细胞通过在表皮下产生胶原蛋白和其他结构/支持蛋白来提供结构支持。成纤维细胞还产生胰岛素样生长因子-1（IGF-1），其与角质形成细胞上的IGF-1受体（IGF-1 R）结合以激活调节细胞增殖和细胞对遗传毒性应激源（如紫外线B辐射）的反应的信号传导途径。我们的研究小组已经确定，由于老年人真皮中成纤维细胞衰老而导致的IGF-1表达的缺乏与皮肤癌发病率的增加有关。目前的研究测试了这一假设，即促能剂肌酸一水合物（Cr）和烟酰胺（NAM）可以保护正常皮肤人成纤维细胞（DHF）免受实验诱导的衰老。为此，我们使用了一种衰老的实验模型，其中原发性DHF在体外用过氧化氢（H2 O2）处理，通过染色β-半乳糖苷酶活性、p21蛋白表达和衰老相关分泌表型细胞因子mRNA水平来测量衰老。我们还测定了H2 O2对IGF-1 mRNA和蛋白表达的影响。我们的研究表明，Cr或NAM预处理保护DHF免受H2 O2诱导的细胞衰老。用H2 O2后的促能剂处理没有效果。此外，这些试剂还抑制了H2 O2处理产生的活性氧。这些研究表明了一种潜在的策略，用于保护老年皮肤中的成纤维细胞免受应激诱导的衰老，这可能会维持IGF-1水平，从而限制表皮角质形成细胞的致癌作用。
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.
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影响因子：
5.5
作者：
Lin Y;Xu Z
通讯作者：
Xu Z
肌酸阻止了肌源性，氧化压力C2C12细胞的线粒体对线粒体的结构和功能损害，并恢复其分化能力。
影响因子：
--
作者：
Barbieri E;Guescini M;Calcabrini C;Vallorani L;Diaz AR;Fimognari C;Canonico B;Luchetti F;Papa S;Battistelli M;Falcieri E;Romanello V;Sandri M;Stocchi V;Ciacci C;Sestili P
通讯作者：
Sestili P
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
DOI：
10.3390/molecules22030356
发表时间：
2017-02-26
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Kemp MG;Spandau DF;Travers JB
通讯作者：
Travers JB
DOI：
10.1016/j.jbc.2021.100570
发表时间：
2021-01
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Hutcherson RJ;Gabbard RD;Castellanos AJ;Travers JB;Kemp MG
通讯作者：
Kemp MG