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天然植物化合物香芹酚对 UVA 和 UVB 联合诱导的大鼠皮肤损伤内质网应激的预防作用。

The preventive effects of natural plant compound carvacrol against combined UVA and UVB-induced endoplasmic reticulum stress in skin damage of rats.

机构信息

Department of Medical Biology, Faculty of Medicine, Van Yuzuncu Yil University, Van, Turkey.

Department of Dermatology, Faculty of Medicine, Van Yuzuncu Yil University, Van, Turkey.

出版信息

Photochem Photobiol Sci. 2024 Sep;23(9):1783-1790. doi: 10.1007/s43630-024-00631-5. Epub 2024 Sep 9.

Abstract

The skin is constantly exposed to a variety of environmental stressors, including ultraviolet (UV) radiation. Exposure of the skin to UV radiation causes a number of detrimental biological damages such as endoplasmic reticulum (ER) stress. The ER stress response is a cytoprotective mechanism that maintains homeostasis of the ER by increasing the capacity of the ER against the accumulation of unfolded proteins in the ER. Carvacrol (CRV) is a monoterpenoid phenol found in essential oils with antimicrobial and anti-inflammatory activities. We investigated for the first time in the literature the potential protective role of CRV against combined UVA and UVB-induced skin damage by targeting the ER stress pathway in a rat model. For this purpose, expressions of Grp78, Perk, Atf6, Ire-1, Chop, Xbp1, Casp12, elF2α, and Traf2 genes related to ER stress were analyzed by RT-PCR and protein expression levels of GRP78, ATF6, CHOP, and XBP1 were determined by ELISA assay in tissue sections taken from the back of the rats. As a result of analysis, it was seen that the expression levels of aforementioned ER stress genes increased significantly in the UVA + UVB irradiated group compared to the control group, while their expression levels decreased markedly by supplementation of CRV in UVA + UVB + CRV group. With regard to expressions of foregoing proteins, their levels escalated notably with UVA + UVB application and decreased markedly by CRV supplementation. In conclusion, present study revealed that CRV ameliorates UVA + UVB-induced ER stress via reducing the expression of mRNA as well as proteins involved in the unfolded protein response (UPR) pathway and inducing apoptosis as evidenced from high Caspase12 level.

摘要

皮肤不断暴露于各种环境应激源,包括紫外线 (UV) 辐射。皮肤暴露于 UV 辐射会导致许多有害的生物学损伤,如内质网 (ER) 应激。ER 应激反应是一种细胞保护机制,通过增加 ER 对 ER 中未折叠蛋白积累的抵抗力来维持 ER 的内稳态。香芹酚 (CRV) 是一种存在于精油中的单萜酚类化合物,具有抗菌和抗炎活性。我们首次在文献中研究了 CRV 通过靶向 ER 应激途径在大鼠模型中对 UVA 和 UVB 联合诱导的皮肤损伤的潜在保护作用。为此,通过 RT-PCR 分析了与 ER 应激相关的 Grp78、Perk、Atf6、Ire-1、Chop、Xbp1、Casp12、elF2α 和 Traf2 基因的表达,通过 ELISA 测定了组织切片中 GRP78、ATF6、CHOP 和 XBP1 的蛋白表达水平取自大鼠背部。分析结果表明,与对照组相比,UVA+UVB 照射组上述 ER 应激基因的表达水平显著升高,而 UVA+UVB+CRV 组补充 CRV 后其表达水平明显降低。关于前述蛋白的表达,它们的水平随着 UVA+UVB 的应用而显著升高,并在 CRV 补充后明显降低。总之,本研究表明,CRV 通过降低未折叠蛋白反应 (UPR) 途径中涉及的 mRNA 以及蛋白的表达,同时诱导细胞凋亡(证据是 Caspase12 水平升高),从而改善 UVA+UVB 诱导的 ER 应激。

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