Taira Junsei, Tsuda Ryuji, Miyagi-Shiohira Chika, Noguchi Hirofumi, Ogi Takayuki
Department of Bioresources Engineering, National Institute of Technology, Okinawa College, Okinawa 905-2192, Japan.
Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.
Antioxidants (Basel). 2023 Mar 10;12(3):693. doi: 10.3390/antiox12030693.
The low-level antioxidant activity of pancreatic islets causes type 1 diabetes due to oxidative stress, which is also the cause of failure in the pancreatic islets' isolation and cell transplantation. In our previous study, pteryxin was found to be a natural product as a nuclear factor-erythroid-2-related factor (Nrf2) activator. This study focused on elucidation that the potentiality of pteryxin can activate the antioxidant enzymes, even under oxidative stress, by hydrogen peroxide (HO). Pteryxin treated with mouse insulinoma MIN6 cells was enhanced the antioxidant gene expressions in the ARE (antioxidant response element) region for HO-1 (Heme Oxygenase-1), GCLC (Glutamate-cysteine ligase catalytic subunit), SOD1 (Super Oxide dismutase1), and Trxr1 (Thioredoxin reductase1), and those enzymes were also expressed during the nuclei transference of cytoplasmic Nrf2. In fact, the cells exposed to HO concentrations of a half-cell lethal in the presence of pteryxin were then induced main antioxidant enzymes, HO-1, GCLC, and Trxr1 in the ARE region. The increased glutathione (GSH) levels associated with the GCLC expression also suggested to be cytoprotective against oxidative stress by activating the redox-metabolizing enzymes involving their increased antioxidant activity in the cells. In addition, Akt is a modulator for Nrf2, which may be responsible for the Nrf2 activation. These results allowed us to consider whether pteryxin or its synthesized congeners, an Nrf2 activator, is a potential preservative agent against islet isolation during cell transplantation.
胰岛的低水平抗氧化活性会因氧化应激导致1型糖尿病，而氧化应激也是胰岛分离和细胞移植失败的原因。在我们之前的研究中，发现蝶芪是一种作为核因子红细胞2相关因子（Nrf2）激活剂的天然产物。本研究聚焦于阐明蝶芪的潜力，即即使在氧化应激下，它也能通过过氧化氢（HO）激活抗氧化酶。用小鼠胰岛素瘤MIN6细胞处理蝶芪可增强抗氧化反应元件（ARE）区域中HO-1（血红素加氧酶-1）、GCLC（谷氨酸-半胱氨酸连接酶催化亚基）、SOD1（超氧化物歧化酶1）和Trxr1（硫氧还蛋白还原酶1）的抗氧化基因表达，并且这些酶在细胞质Nrf2的核转位过程中也会表达。事实上，在存在蝶芪的情况下，暴露于半细胞致死浓度HO的细胞随后在ARE区域诱导出主要的抗氧化酶HO-1、GCLC和Trxr1。与GCLC表达相关的谷胱甘肽（GSH）水平升高也表明，通过激活细胞中参与其抗氧化活性增加的氧化还原代谢酶，对氧化应激具有细胞保护作用。此外，Akt是Nrf2的调节剂，可能负责Nrf2的激活。这些结果使我们思考蝶芪或其合成类似物（一种Nrf2激活剂）是否是细胞移植过程中胰岛分离的潜在保护剂。
