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DbGTi 蛋白通过激活斑马鱼(Danio rerio)幼虫模型中的 Nrf2/HO-1 信号通路来减轻六价铬诱导的氧化应激。

DbGTi protein attenuates chromium (VI)-induced oxidative stress via activation of the Nrf2/HO-1 signalling pathway in zebrafish (Danio rerio) larval model.

机构信息

Department of Biotechnology, School of Bio-Engineering, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India; Interdisciplinary Institute of Indian System of Medicine, SRM Institute of Science and Technology, Kattankulathur 603 203, Tamil Nadu, India.

Institute of Biotechnology, Department of Medical Biotechnology and Integrative Physiology, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Saveetha Nagar, Thandalam, Kanchipuram, Tamil Nadu, India.

出版信息

Int J Biol Macromol. 2024 Nov;280(Pt 4):136099. doi: 10.1016/j.ijbiomac.2024.136099. Epub 2024 Sep 28.

DOI:10.1016/j.ijbiomac.2024.136099
PMID:39343269
Abstract

Hexavalent chromium (Cr (VI)) contamination poses a significant threat to environmental and human health due to its ability to induce oxidative stress. Conventional strategies to counter Cr (VI)-induced oxidative stress, like antioxidants and chelating agents, face efficacy limitations and adverse effects. The present study is intended to counteract the limitations of conventional strategies by introducing a trypsin inhibitor isolated from Dioscorea bulbifera L. tubers, known as DbGTi protein, against Cr (VI)-induced developmental toxicity and oxidative stress. Through a comprehensive array of biochemical assays, behavioural tests, and gene expression analyses, this study interprets the underlying mechanisms of the DbGTi protein. Results demonstrated that the DbGTi protein effectively restored antioxidant defense systems, including superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione S-transferase (GST), and glutathione peroxidase (GTPx), thereby mitigating cellular damage, reducing cell death, and enhancing neuro-biomarkers. qRT-PCR analysis of mRNA expression profiling revealed the upregulation of genes associated with antioxidant defense (sod, cat, gpx) and defense pathway (nrf2, hmox-1a), further highlighting the protective effects of DbGTi protein against Cr (VI)-induced oxidative stress.

摘要

六价铬 (Cr (VI)) 污染因其诱导氧化应激的能力而对环境和人类健康构成重大威胁。对抗 Cr (VI) 诱导的氧化应激的传统策略,如抗氧化剂和螯合剂,面临着功效限制和不良反应的问题。本研究旨在通过引入从山药块茎中分离出的一种胰蛋白酶抑制剂,即 DbGTi 蛋白,来克服传统策略的局限性,以对抗 Cr (VI) 诱导的发育毒性和氧化应激。通过一系列全面的生化分析、行为测试和基因表达分析,本研究解释了 DbGTi 蛋白的潜在机制。结果表明,DbGTi 蛋白有效地恢复了抗氧化防御系统,包括超氧化物歧化酶 (SOD)、过氧化氢酶 (CAT)、谷胱甘肽 (GSH)、谷胱甘肽 S-转移酶 (GST) 和谷胱甘肽过氧化物酶 (GTPx),从而减轻细胞损伤、减少细胞死亡并增强神经生物标志物。mRNA 表达谱的 qRT-PCR 分析显示,与抗氧化防御 (sod、cat、gpx) 和防御途径 (nrf2、hmox-1a) 相关的基因上调,进一步强调了 DbGTi 蛋白对 Cr (VI) 诱导的氧化应激的保护作用。

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