Alpha-Tocopherol Protects Human Dermal Fibroblasts by Modulating Nitric Oxide Release, Mitochondrial Function, Redox Status, and Inflammation.

IF 2.8 4区 医学 Q2 DERMATOLOGY Skin Pharmacology and Physiology Pub Date : 2022-01-01 Epub Date: 2021-07-08 DOI:10.1159/000517204
Lara Camillo, Elena Grossini, Serena Farruggio, Patrizia Marotta, Laura Cristina Gironi, Elisa Zavattaro, Paola Savoia
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引用次数: 6

Abstract

Background: The altered balance between oxidants/antioxidants and inflammation, changes in nitric oxide (NO) release, and mitochondrial function have a role in skin aging through fibroblast modulation. Tocopherol is promising in counteracting the abovementioned events, but the effective mechanism of action needs to be clarified.

Objective: The aim of this study was to examine the effects of α-tocopherol on cell viability/proliferation, NO release, mitochondrial function, oxidants/antioxidants, and inflammation in human dermal fibroblasts (HDF) subjected to oxidative stress.

Methods: HDF were treated with H2O2 in the presence or absence of 1-10 μM α-tocopherol. Cell viability, reactive oxygen species (ROS), NO release, and mitochondrial membrane potential were measured; glutathione (GSH), superoxide dismutase (SOD)-1 and -2, glutathione peroxidase-1 (GPX-1), inducible NO synthase (iNOS), and Ki-67 were evaluated by RT-PCR and immunofluorescence; cell cycle was analyzed using FACS. Pro- and anti-inflammatory cytokine gene expression was analyzed through qRT-PCR.

Results: α-Tocopherol counteracts H2O2, although it remains unclear whether this effect is dose dependent. Improvement of cell viability, mitochondrial membrane potential, Ki-67 expression, and G0/G1 and G2/M phases of the cell cycle was observed. These effects were accompanied by the increase of GSH content and the reduction of SOD-1 and -2, GPX-1, and ROS release. Also, iNOS expression and NO release were inhibited, and pro-inflammatory cytokine gene expression was decreased, confirming the putative role of α-tocopherol against inflammation.

Conclusion: α-Tocopherol exerts protective effects in HDF which underwent oxidative stress by modulating the redox status, inflammation, iNOS-dependent NO release, and mitochondrial function. These observations have a potential role in the prevention and treatment of photoaging-related skin cancers.

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α -生育酚通过调节一氧化氮释放、线粒体功能、氧化还原状态和炎症来保护人皮肤成纤维细胞。
背景:氧化剂/抗氧化剂与炎症之间平衡的改变、一氧化氮(NO)释放的变化和线粒体功能通过成纤维细胞调节在皮肤衰老中发挥作用。生育酚对上述事件有拮抗作用,但其作用机制尚不清楚。目的:研究α-生育酚对氧化应激下人真皮成纤维细胞(HDF)细胞活力/增殖、NO释放、线粒体功能、氧化剂/抗氧化剂和炎症的影响。方法:在1 ~ 10 μM α-生育酚存在或不存在的条件下,用H2O2处理HDF。测定细胞活力、活性氧(ROS)、NO释放量和线粒体膜电位;采用RT-PCR和免疫荧光法检测谷胱甘肽(GSH)、超氧化物歧化酶(SOD)-1和-2、谷胱甘肽过氧化物酶-1 (GPX-1)、诱导型NO合成酶(iNOS)和Ki-67;流式细胞仪分析细胞周期。采用qRT-PCR分析促炎性和抗炎性细胞因子基因表达。结果:α-生育酚可抵消H2O2,尽管尚不清楚这种作用是否与剂量有关。观察到细胞活力、线粒体膜电位、Ki-67表达以及细胞周期G0/G1和G2/M期的改善。这些影响伴随着GSH含量的增加,SOD-1和-2、GPX-1和ROS释放的减少。iNOS表达和NO释放均受到抑制,促炎细胞因子基因表达降低,证实了α-生育酚抗炎症的作用。结论:α-生育酚通过调节氧化还原状态、炎症反应、inos依赖性NO释放和线粒体功能对氧化应激的HDF具有保护作用。这些观察结果对光老化相关皮肤癌的预防和治疗具有潜在的作用。
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来源期刊
Skin Pharmacology and Physiology
Skin Pharmacology and Physiology 医学-皮肤病学
CiteScore
5.20
自引率
7.40%
发文量
23
审稿时长
>12 weeks
期刊介绍: In the past decade research into skin pharmacology has rapidly developed with new and promising drugs and therapeutic concepts being introduced regularly. Recently, the use of nanoparticles for drug delivery in dermatology and cosmetology has become a topic of intensive research, yielding remarkable and in part surprising results. Another topic of current research is the use of tissue tolerable plasma in wound treatment. Stimulating not only wound healing processes but also the penetration of topically applied substances into the skin, this novel technique is expected to deliver very interesting results.
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