Protective Effect of Marine Peptide from Netunea arthritica cumingii Against Gentamicin-Induced Hair Cell Damage in Zebrafish.

IF 4.9 2区 医学 Q1 CHEMISTRY, MEDICINAL Marine Drugs Pub Date : 2024-11-16 DOI:10.3390/md22110519
Hongbao Zheng, Ranran Zhu, Yun Zhang, Kechun Liu, Qing Xia, Peihai Li, Xiaoyue Sun, Chen Sun, Shanshan Zhang
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Abstract

Auditory hair cell damage induced by aminoglycoside antibiotics (AmAn) leads to hearing loss, which has a serious effect on people's mental and physical health. This ototoxicity is thought to be related with the excessive accumulation of reactive oxygen species (ROS) in hair cells. However, therapeutic agents that protect hair cells are limited. Marine peptides have been shown to have excellent potential applications in disease prevention and treatment. Therefore, this study investigated the protective effects of an active peptide from Neptunea arthritica cumingii against AmAn-induced hair cell damage using the model of hair cell damage zebrafish. We identified the number, ultrastructure, and function of hair cells using fluorescence probes and scanning electron microscopy. The uptake of AmAn, ROS level, mitochondrial permeability transition pore, and apoptosis in hair cells were also tested by fluorescence labeling and TUNEL assay. The molecular mechanism for hair cell protection exerted by the peptide was detected by a real-time quantitative PCR assay. The results indicated that the peptide suppressed the uptake of AmAn but did not damage the function of hair cells mediating hearing. It also prevented ROS accumulation, decreased the occurrence of apoptosis, and rescued the abnormal opening and expressions of mitochondrial permeability transition pore and genes related to antioxidants. The peptide may be an effective therapeutic agent for AmAn-induced ototoxicity. In the future, we plan to use mammalian models to further investigate the otoprotective effect of the peptide.

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网纹草海洋肽对庆大霉素诱导的斑马鱼毛细胞损伤的保护作用
氨基糖苷类抗生素(AmAn)引起的听觉毛细胞损伤会导致听力损失,严重影响人们的身心健康。这种耳毒性被认为与毛细胞中活性氧(ROS)的过度积累有关。然而,保护毛细胞的治疗药物却很有限。海洋肽已被证明在疾病预防和治疗方面具有很好的应用潜力。因此,本研究以毛细胞损伤模型斑马鱼为对象,研究了海王星节肢动物中的一种活性肽对氨诱导的毛细胞损伤的保护作用。我们使用荧光探针和扫描电子显微镜鉴定了毛细胞的数量、超微结构和功能。我们还通过荧光标记和 TUNEL 试验检测了毛细胞对 AmAn 的吸收、ROS 水平、线粒体通透性转换孔和凋亡。实时定量 PCR 检测了该肽保护毛细胞的分子机制。结果表明,该肽抑制了对 AmAn 的吸收,但没有损害毛细胞介导听力的功能。它还能阻止 ROS 的积累,减少细胞凋亡的发生,挽救线粒体通透性转换孔和抗氧化剂相关基因的异常开放和表达。该肽可能是氨酪酸诱导的耳毒性的有效治疗药物。今后,我们计划利用哺乳动物模型进一步研究该肽的耳保护作用。
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来源期刊
Marine Drugs
Marine Drugs 医学-医药化学
CiteScore
9.60
自引率
14.80%
发文量
671
审稿时长
1 months
期刊介绍: Marine Drugs (ISSN 1660-3397) publishes reviews, regular research papers and short notes on the research, development and production of drugs from the sea. Our aim is to encourage scientists to publish their experimental and theoretical research in as much detail as possible, particularly synthetic procedures and characterization information for bioactive compounds. There is no restriction on the length of the experimental section.
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