Xiangya School of Public Health, Central South University, Changsha 410128, Hunan, China.
Department of Public Health Emergency Treatment, Hunan Center for Disease Control and Prevention (CDC), Changsha 410005, Hunan, China.
Toxins (Basel). 2019 Jul 12;11(7):403. doi: 10.3390/toxins11070403.
Microcystin-LR (MC-LR), a cyanotoxin produced by cyanobacteria, induces oxidative stress in various types of cells. Prodigiosin, a red linear tripyrrole pigment, has been recently reported to have antimicrobial, antioxidative, and anticancer properties. How prodigiosin reacts to reactive oxygen species (ROS) induced by MC-LR is still undetermined. This study aimed to examine the effect of prodigiosin against oxidative stress induced by MC-LR in HepG2 cells. Ros was generated after cells were treated with MC-LR and was significantly inhibited with treatment of prodigiosin. In prodigiosin-treated cells, the levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and Nrf2-related phase II enzyme heme oxygenase-1 (HO-1) were increased. Besides, prodigiosin contributed to enhance nuclear Nrf2 level and repressed ubiquitination. Furthermore, prodigiosin promoted Nrf2 protein level and inhibited ROS in Nrf2 knocked down HepG2 cells. Results indicated that prodigiosin reduced ROS induced by MC-LR by enhancing Nrf2 translocation into the nucleus in HepG2 cells. The finding presents new clues for the potential clinical applications of prodigiosin for inhibiting MC-LR-induced oxidative injury in the future.
微囊藻毒素-LR（MC-LR）是一种由蓝藻产生的细胞毒素，可诱导多种类型的细胞产生氧化应激。灵菌红素是一种红色线性三吡咯色素，最近有报道称其具有抗菌、抗氧化和抗癌特性。灵菌红素如何应对 MC-LR 诱导的活性氧（ROS）仍不确定。本研究旨在研究灵菌红素对 HepG2 细胞中由 MC-LR 诱导的氧化应激的影响。ROS 在细胞用 MC-LR 处理后产生，并用灵菌红素处理可显著抑制 ROS 的产生。在灵菌红素处理的细胞中，核因子红细胞 2 相关因子 2（Nrf2）和 Nrf2 相关的 II 期酶血红素加氧酶-1（HO-1）的水平增加。此外，灵菌红素有助于增强核 Nrf2 水平并抑制泛素化。此外，灵菌红素促进 Nrf2 蛋白水平并抑制 Nrf2 敲低 HepG2 细胞中的 ROS。结果表明，灵菌红素通过增强 Nrf2 向细胞核的易位来减少 MC-LR 诱导的 ROS 在 HepG2 细胞中的产生。这一发现为灵菌红素在未来抑制 MC-LR 诱导的氧化损伤的潜在临床应用提供了新的线索。
