研究动态
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通过在体外调节Nrf2/HO-1信号通路的蛋白酶SH21,减轻氧化损伤,发挥抗炎和抗癌特性。

Attenuation of Oxidative Damage via Upregulating Nrf2/HO-1 Signaling Pathway by Protease SH21 with Exerting Anti-Inflammatory and Anticancer Properties In Vitro.

发表日期:2023 Sep 01
作者: Hasan Tarek, Seung Sik Cho, Md Selim Hossain, Jin Cheol Yoo
来源: ANTIOXIDANTS & REDOX SIGNALING

摘要:

氧化损伤和炎症是与癌症和其他退行性疾病相关的非常重要的方面之一。在本研究中,我们调查了从暹罗芽孢杆菌纯化得到的一个25 kDa蛋白酶(SH21)的生物活性。SH21表现出很强的抗氧化和抑制活性氧种(ROS)生成的能力,并呈剂量依赖性。SH21处理后,抗氧化酶如超氧化物歧化酶1(SOD1)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶1(GPx-1)的mRNA和蛋白水平得到增强。SH21还通过增加转录和翻译活性因子NF-E2相关因子2(Nrf2)的活性,进而促进了解毒酶血红素加氧酶-1(HO-1)的生成。此外,SH21通过抑制一氧化氮(NO)和促炎细胞因子如TNF-α、IL-6和IL-1β在脂多糖(LPS)刺激下的产生,显示出潜在的抗炎活性。在60、80和100 μg/mL的浓度下,SH21能够抑制一氧化氮合酶(iNOS)和细胞因子基因的表达。此外,SH21以浓度依赖的方式显著释放乳酸脱氢酶(LDH)酶,并对HL-60、A549和Hela等三种测试癌细胞系表现出强烈的抑制活性。我们的结果表明,SH21具有有效的抗氧化、抗炎和抗癌作用,可能是一种很好的治疗剂对抗与炎症相关的疾病。
Oxidative damage and inflammation are among the very significant aspects interrelated with cancer and other degenerative diseases. In this study, we investigated the biological activities of a 25 kDa protease (SH21) that was purified from Bacillus siamensis. SH21 exhibited very powerful antioxidant and reactive oxygen species (ROS) generation inhibition activity in a dose-dependent approach. The mRNA and protein levels of antioxidant enzymes such as superoxide dismutase 1 (SOD1), catalase (CAT), and glutathione peroxidase 1 (GPx-1) were enhanced in the SH21-treated sample. SH21 also increased the transcriptional and translational activities of NF-E2-related factor 2 (Nrf2) with the subsequent development of detoxifying enzyme heme oxygenase-1 (HO-1). In addition, SH21 showed potential anti-inflammatory activity via inhibition of nitric oxide (NO) and proinflammatory cytokines, such as TNF-α, IL-6, and IL-1β, production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. At concentrations of 60, 80, and 100 μg/mL, SH21 potentially suppressed nitric oxide synthase (iNOS) and cytokine gene expressions. Furthermore, SH21 significantly released lactate dehydrogenase (LDH) enzyme in cancer cell supernatant in a concentration-dependent manner and showed strong activity against three tested cancer cell lines, including HL-60, A549, and Hela. Our results suggest that SH21 has effective antioxidant, anti-inflammatory, and anticancer effects and could be an excellent therapeutic agent against inflammation-related diseases.