UVA Induced Oxidative Stress Was Inhibited by Paeoniflorin/Nrf2 Signaling or PLIN2
UVA Induced Oxidative Stress Was Inhibited by Paeoniflorin/Nrf2 Signaling or PLIN2
复制标题
芍药苷/Nrf 2信号通路或PLIN 2抑制UVA诱导的氧化应激
DOI：
10.3389/fphar.2020.00736
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发表时间：
2020-05-15
影响因子：
5.6
通讯作者：
Chen, Hong-duo
中科院分区：
文献类型：
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作者：
Lu, Yan-Song;Jiang, Yuan;Chen, Hong-duo
UVA辐射引起的氧化损伤引起的光损伤与光老化和皮肤癌密切相关。芍药苷(PF)是从牡丹根中提取的一种有效的抗氧化剂。Plin2被称为脂肪分化相关蛋白，以前参与了氧化应激的调节。在本研究中，我们试图研究PF和PLIN2对UVA辐射的人皮肤成纤维细胞(HDFS)的光保护作用。用800 mU/M的PF和22.5J/cm2的UVA照射HDF。检测MTS活性、细胞凋亡率、ROS、丙二醛(MDA)和超氧化物歧化酶(SOD)。用RT-qPCR或Western印迹法检测Nrf2、HO-1、NQ-O1和PLIN2的表达。NRF2被siRNA沉默，PLIN2在病毒转导中高表达。与UVA辐射相比，PF预处理能显著提高MTS活性，减少细胞凋亡率，减少ROS和MDA的生成，提高SOD活性，增加Nrf2及其靶基因HO-1和NQ-O1的表达。当NRF2被击倒时，PF失去了以上的保护性能。此外，UVA诱导的氧化应激导致PLIN2表达上调，而PF可降低PLIN2的表达。过表达PLIN2可提高HDFS中MTS活性，降低MDA水平。联合应用PLIN2过表达和PF预处理可共同抑制UVA诱导的损伤。此外，我们还发现PF和PLIN2对UVA诱导的氧化应激具有代偿保护作用。综上所述，我们的研究表明，PfviaNrf2/HO-1/NQ-O1信号通路或PLIN2可以抑制UVA诱导的光损伤，PLIN2过表达和Pf的共同作用对UVA相关的氧化应激具有相加作用。
Photodamages caused by UVA radiation induced oxidative injuries are closely related to photoaging and skin cancer. Paeoniflorin (PF), extracted from the root of Paeonia lactiflora, has been reported to be an effective antioxidant. PLIN2, known as adipose differentiation-related protein, has been previously involved in the regulation of oxidative stress. In this study, we were sought to investigate the photo-protective property of PF and PLIN2 in UVA-radiated human dermal fibroblasts (HDFs). HDFs were pre-treated with PF (800 mu M) followed by UVA radiation (22.5 J/cm2). MTS activity, cell apoptosis, ROS, MDA, and SOD were detected, respectively. The expressions of Nrf2, HO-1, NQ-O1, and PLIN2 were determined using RT-qPCR or western blot. Nrf2 was silenced by siRNA, and PLIN2 was overexpressedvialentiviral transduction. Comparing to the UVA radiation, PF pre-treatment could prominently increase the MTS activity, decrease cell apoptosis, reduce the generations of ROS and MDA, increase the activity of SOD and increase the expression of Nrf2 and its target genes HO-1 and NQ-O1. When Nrf2 was knocked down, PF lost above protective properties. In addition, UVA induced oxidative stress led to upregulation of PLIN2 and the latter could be decreased by PF. Overexpression of PLIN2 improved MTS activity and reduced MDA level in HDFs. The combination of PLIN2 overexpression and PF pre-treatment corporately inhibited UVA-induced injury. Besides, we also found that PF and PLIN2 had a compensatory protection against UVA induced oxidative stress. In conclusion, our study demonstrated that UVA induced photodamages could be inhibited by PFviaNrf2/HO-1/NQ-O1 signaling pathway or by PLIN2, and the combination of PLIN2 overexpression and PF played additive effects against UVA-related oxidative stress.