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岗田酸可增强斑马鱼幼鱼脑组织中 NFKB、TLR-4、Caspase 3、ERK ½、c-FOS 和 8-OHdG 信号通路的激活。

Okadaic acid enhances NfKB, TLR-4, caspase 3, ERK ½, c-FOS, and 8-OHdG signaling pathways activation in brain tissues of zebrafish larvae.

机构信息

Department of Basic Sciences, Faculty of Fisheries, Atatürk University, TR-25030, Erzurum, Turkey.

Department of Basic Sciences, Faculty of Fisheries, Atatürk University, TR-25030, Erzurum, Turkey.

出版信息

Fish Shellfish Immunol. 2024 Jun;149:109529. doi: 10.1016/j.fsi.2024.109529. Epub 2024 Mar 30.

DOI:10.1016/j.fsi.2024.109529
PMID:38561069
Abstract

This study was designed to investigate the potential neuronal damage mechanism of the okadaic acid (OA) in the brain tissues of zebrafish embryos by evaluating in terms of immunofluorescence of Nf KB, TLR-4, caspase 3, ERK ½, c-FOS and 8-OHdG signaling pathways. We also evaluated body malformations. For this purpose, zebrafish embryos were exposed to 0.5 μg/ml, 1 μg/ml and 2.5 μg/ml of OA for 5 days. After application, FITC/GFP labeled protein-specific antibodies were used in immunofluorescence assay for NfKB, TLR-4, caspase 3, ERK ½, c-FOS and 8-OHdG respectively. The results indicated that OA caused immunofluorescence positivity of NfKB, TLR-4, caspase 3, ERK ½, c-FOS and 8-OHdG in a dose-dependent manner in the brain tissues of zebrafish embryos. Pericardial edema (PE), nutrient sac edema (YSE) and body malformations, tail malformation, short tail and head malformation (BM) were detected in zebrafish embryos. These results suggest that OA induces neuronal damage by affecting the modulation of DNA damage, apoptotic, and inflammatory activities in the brain tissues of zebrafish embryos. The increase in signaling pathways shows that OA can cause damage in the structure and function of brain nerve cells. Our results provide a new basis for the comprehensive assessment of the neural damage of OA and will offer enable us to better understand molecular the mechanisms underlying the pathophysiology of OA toxicity.

摘要

本研究旨在通过评估 okadaic 酸 (OA) 在斑马鱼胚胎脑组织中 NF-κB、TLR-4、caspase 3、ERK ½、c-FOS 和 8-OHdG 信号通路的免疫荧光,研究其潜在的神经元损伤机制。我们还评估了身体畸形。为此,将斑马鱼胚胎暴露于 0.5μg/ml、1μg/ml 和 2.5μg/ml 的 OA 中 5 天。应用后,用 FITC/GFP 标记的蛋白特异性抗体进行免疫荧光测定,分别检测 NF-κB、TLR-4、caspase 3、ERK ½、c-FOS 和 8-OHdG。结果表明,OA 以剂量依赖的方式在斑马鱼胚胎脑组织中引起 NF-κB、TLR-4、caspase 3、ERK ½、c-FOS 和 8-OHdG 的免疫荧光阳性。在斑马鱼胚胎中检测到心包水肿 (PE)、营养囊水肿 (YSE) 和身体畸形、尾巴畸形、短尾和头部畸形 (BM)。这些结果表明,OA 通过影响 DNA 损伤、凋亡和炎症活性的调节,导致斑马鱼胚胎脑组织中的神经元损伤。信号通路的增加表明 OA 可导致脑神经元细胞的结构和功能受损。我们的研究结果为综合评估 OA 的神经损伤提供了新的依据,并将有助于我们更好地理解 OA 毒性的病理生理学的分子机制。

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