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蛋白质-脂质复合物:分子结构、当前研究情况及细胞毒性机制

Protein-lipid complexes: molecular structure, current scenarios and mechanisms of cytotoxicity.

作者信息

El-Fakharany Esmail M, Redwan Elrashdy M

机构信息

Protein Research Department, Genetic Engineering and Biotechnology Research Institute, City for Scientific Research and Technology Applications (SRTA-City) New Borg EL-Arab 21934 Alexandria Egypt

Department of Biological Sciences, Faculty of Sciences, King Abdulaziz University P. O. Box 80203 Jeddah Saudi Arabia.

出版信息

RSC Adv. 2019 Nov 13;9(63):36890-36906. doi: 10.1039/c9ra07127j. eCollection 2019 Nov 11.

DOI:10.1039/c9ra07127j
PMID:35539089
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9075609/
Abstract

Some natural proteins can be complexed with oleic acid (OA) to form an active protein-lipid formulation that can induce tumor-selective apoptosis. The first explored protein was human milk α-lactalbumin (α-LA), called HAMLET when composed with OA in antitumor form. Several groups have prepared active protein-lipid complexes using a variety of approaches, all of which depend on target protein destabilization or direct OA-protein incubation to alter pH to acid or alkaline condition. In addition to performing vital roles in inflammatory processes and immune responses, fatty acids can disturb different metabolic pathways and cellular signals. Therefore, the tumoricidal action of these complexes is related to OA rather than the protein that keeps OA in solution and acts as a vehicle for transferring OA molecules to tumor cells. However, other studies have suggested that the antitumor efficacy of these complexes was exerted by both protein and OA together. The potential is not limited to the anti-tumor activity of protein-lipid complexes but extends to other functions such as bactericidal activity. The protein shell enhances the solubility and stability of the bound fatty acid. These protein-lipid complexes are promising candidates for fighting various cancer types and managing bacterial and viral infections.

摘要

一些天然蛋白质可与油酸(OA)复合,形成一种能诱导肿瘤选择性凋亡的活性蛋白质 - 脂质制剂。最早被研究的蛋白质是人乳α - 乳白蛋白(α - LA),当它与OA以抗肿瘤形式结合时被称为HAMLET。多个研究小组采用了多种方法制备活性蛋白质 - 脂质复合物,所有这些方法都依赖于目标蛋白质的去稳定化或直接将OA与蛋白质孵育,以将pH改变为酸性或碱性条件。脂肪酸除了在炎症过程和免疫反应中发挥重要作用外,还能干扰不同的代谢途径和细胞信号。因此,这些复合物的杀肿瘤作用与OA有关,而不是与将OA保持在溶液中并作为将OA分子转移到肿瘤细胞的载体的蛋白质有关。然而,其他研究表明,这些复合物的抗肿瘤功效是由蛋白质和OA共同发挥的。其潜力不仅限于蛋白质 - 脂质复合物的抗肿瘤活性,还扩展到其他功能,如杀菌活性。蛋白质外壳增强了结合脂肪酸的溶解度和稳定性。这些蛋白质 - 脂质复合物有望成为对抗各种癌症类型以及控制细菌和病毒感染的候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c58a/9075609/8db2973aab83/c9ra07127j-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c58a/9075609/6060a3af61dd/c9ra07127j-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c58a/9075609/1acdc3c063d1/c9ra07127j-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c58a/9075609/9eb22b09f559/c9ra07127j-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c58a/9075609/12a93fa902c4/c9ra07127j-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c58a/9075609/8db2973aab83/c9ra07127j-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c58a/9075609/6060a3af61dd/c9ra07127j-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c58a/9075609/1acdc3c063d1/c9ra07127j-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c58a/9075609/9eb22b09f559/c9ra07127j-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c58a/9075609/12a93fa902c4/c9ra07127j-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c58a/9075609/8db2973aab83/c9ra07127j-f5.jpg

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Effect of alpha-lactalbumin and lactoferrin oleic acid complexes on chromatin structural organization.α-乳白蛋白和乳铁蛋白油酸复合物对染色质结构组织的影响。
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