Institute of Biotechnology, Department of Medical Biotechnology and Integrative Physiology, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Thandalam, Chennai, 602 105, Tamil Nadu, India.
Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
Mol Biol Rep. 2024 Sep 17;51(1):990. doi: 10.1007/s11033-024-09905-8.
Oxidative stress, a condition characterized by excessive production of reactive oxygen species (ROS), can cause significant damage to cellular macromolecules, leading to neurodegeneration. This underscores the need for effective antioxidant therapies that can mitigate oxidative stress and its associated neurodegenerative effects. KC14 peptide derived from liver-expressed antimicrobial peptide-2 A (LEAP 2 A) from Cyprinus carpio L. has been identified as a potential therapeutic agent. This study focuses on the antioxidant and neuroprotective properties of the KC14 peptide is to evaluate its effectiveness against oxidative stress and neurodegeneration.
The antioxidant capabilities of KC14 were initially assessed through in silico docking studies, which predicted its potential to interact with oxidative stress-related targets. Subsequently, the peptide was tested at concentrations ranging from 5 to 45 µM in both in vitro and in vivo experiments. In vivo studies involved treating HO-induced zebrafish larvae with KC14 peptide to analyze its effects on oxidative stress and neuroprotection.
KC14 peptide showed a protective effect against the developmental malformations caused by HO stress, restored antioxidant enzyme activity, reduced neuronal damage, and lowered lipid peroxidation and nitric oxide levels in HO-induced larvae. It enhanced acetylcholinesterase activity and significantly reduced intracellular ROS levels (p < 0.05) dose-dependently. Gene expression studies showed up-regulation of antioxidant genes with KC14 treatment under HO stress.
This study highlights the potent antioxidant activity of KC14 and its ability to confer neuroprotection against oxidative stress can provide a novel therapeutic agent for combating neurodegenerative diseases induced by oxidative stress.
氧化应激是一种由活性氧（ROS）过度产生引起的状态，可导致细胞大分子的严重损伤，从而导致神经退行性变。这突显了需要有效的抗氧化治疗方法来减轻氧化应激及其相关的神经退行性作用。从鲤鱼中分离出的肝表达抗菌肽-2A（LEAP 2A）的 KC14 肽已被鉴定为一种潜在的治疗剂。本研究集中于 KC14 肽的抗氧化和神经保护特性，以评估其对氧化应激和神经退行性变的作用。
首先通过计算机对接研究评估 KC14 的抗氧化能力，预测其与氧化应激相关靶标的潜在相互作用。随后，在体外和体内实验中，在 5 至 45 µM 的浓度范围内测试该肽。体内研究涉及用 KC14 肽处理 HO 诱导的斑马鱼幼虫，以分析其对氧化应激和神经保护的影响。
KC14 肽对 HO 应激引起的发育畸形表现出保护作用，恢复抗氧化酶活性，减少神经元损伤，并降低 HO 诱导的幼虫中的脂质过氧化和一氧化氮水平。它还剂量依赖性地增强乙酰胆碱酯酶活性并显著降低细胞内 ROS 水平（p<0.05）。基因表达研究表明，在 HO 应激下，KC14 处理可上调抗氧化基因的表达。
本研究强调了 KC14 的强大抗氧化活性及其对氧化应激引起的神经保护作用的能力，可为对抗氧化应激诱导的神经退行性疾病提供新的治疗剂。
