Small molecular antioxidants effectively protect from PUVA-induced oxidative stress responses underlying fibroblast senescence and photoaging
Small molecular antioxidants effectively protect from PUVA-induced oxidative stress responses underlying fibroblast senescence and photoaging
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DOI：
10.1016/j.freeradbiomed.2008.05.006
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发表时间：
2008-09-01
影响因子：
7.4
通讯作者：
Scharffetter-Kochanek, Karin
中科院分区：
文献类型：
--
作者：
Briganti, Stefania;Wlaschek, Meinhard;Scharffetter-Kochanek, Karin
人类成纤维细胞暴露于8-甲氧基索拉伦和紫外线-A辐射（PUVA）导致胁迫诱导的成纤维细胞衰老。我们在这里研究了抗氧化剂防御系统在活性氧（ROS）积累中的作用以及抗氧化剂A-生育酚，N-乙酰半胱氨酸和A-脂肪酸对PUVA诱导的细胞衰老的作用。 PUVA治疗诱导细胞内ROS的立即产生和增加。用α-生育酚（α-Toc），N-乙酰半胱氨酸（NAC）或α-脂肪酸（alpha-la）补充PUVA处理的成纤维细胞（α-Toc），N-乙酰半胱氨酸（NAC），从而消除了ROS产生的增加，并从依赖ROS的成纤维的变化中救出了增加衰老表型，例如细胞质增大，增强了表达衰老相关的β-半乳糖苷酶和基质 - 甲基蛋白酶1，光导向和内在衰老的标志。 PUVA处理破坏了细胞膜和稳态受损以及细胞抗氧化剂系统的功能，谷胱甘肽和过氧化氧化氧化氧化酶活性的显着降低。补充NAC，Alpha-LA和Alpha-Toc抵消了这些变化。我们的数据提供了因果证据，表明（i）由于整体细胞抗氧化剂的失衡而引起的氧化应激有助于诱导和维持PUVA诱导的成纤维细胞衰老，并且（ii）低分子抗氧化剂有效地保护了这些有害改变。 （c）2008 Elsevier Inc.保留所有权利。
Exposure of human fibroblasts to 8-methoxypsoralen Plus ultraviolet-A irradiation (PUVA) results in stress-induced cellular senescence in fibroblasts. We here studied the role of the antioxidant defense system in the accumulation of reactive oxygen species (ROS) and the effect of the antioxidants a-tocopherol, N-acetylcysteine, and a-lipoic acid on PUVA-induced cellular senescence. PUVA treatment induced an immediate and increasing generation of intracellular ROS. Supplementation of PUVA-treated fibroblasts with alpha-tocopherol (alpha-Toc), N-acetylcysteine (NAC), or alpha-lipoic acid (alpha-LA) abrogated the increased ROS generation and rescued fibroblasts from the ROS-dependent changes into the cellular senescence phenotype, such as cytoplasmic enlargement, enhanced expression of senescence-associated-beta-galactosidase and matrix-metalloproteinase-1, hallmarks of photoaging and intrinsic aging. PUVA treatment disrupted the integrity of cellular membranes and impaired homeostasis and function of the cellular antioxidant system with a significant decrease in glutathione and hydrogen peroxide-detoxifying enzymes activities. Supplementation with NAC, alpha-LA, and alpha-Toc counteracted these changes. Our data provide causal evidence that (i) oxidative stress due to an imbalance in the overall cellular antioxidant capacity contributes to the induction and maintenance of the PUVA-induced fibroblast senescence and that (ii) low molecular antioxidants protect effectively against these deleterious alterations. (c) 2008 Elsevier Inc. All rights reserved.