Rudjer Boskovic Institute, Laboratory for Oxidative Stress, Zagreb, Croatia.
Clinical Hospital Centre Zagreb, Department of Pathology, Zagreb, Croatia.
Neurochem Int. 2021 Oct;149:105118. doi: 10.1016/j.neuint.2021.105118. Epub 2021 Jun 28.
There is a lot of evidence showing that lipid peroxidation plays very important role in development of various diseases, including neurodegenerative diseases and brain tumors. Lipid peroxidation is achieved by two main pathways, by enzymatic or by non-enzymatic oxidation, respectively. In this paper, we focus on non-enzymatic, self-catalyzed chain reaction of poly-unsaturated fatty acid (PUFA) peroxidation generating reactive aldehydes, notably 4-hydroxynonenal (4-HNE), which acts as second messenger of free radicals and as growth regulating factor. It might originate from astrocytes as well as from blood vessels, even within the blood-brain barrier (BBB), which is in case of brain tumors transformed into the blood-brain-tumor barrier (BBTB). The functionality of the BBB is strongly affected by 4-HNE because it forms relatively stable protein adducts thus allowing the persistence and the spread of lipid peroxidation, as revealed by immunohistochemical findings. Because 4-HNE can act as a regulator of vital functions of normal and of malignant cells acting in the cell type- and concentration-dependent manners, the bioactivities of this product of lipid peroxidation be should further studied to reveal if it acts as a co-factor of carcinogenesis or as natural factor of defense against primary brain tumors and metastatic cancer.
有大量证据表明,脂质过氧化在各种疾病的发展中起着非常重要的作用,包括神经退行性疾病和脑肿瘤。脂质过氧化作用是通过两种主要途径实现的,分别是酶促氧化和非酶促氧化。本文重点研究多不饱和脂肪酸(PUFA)过氧化的非酶促、自催化链式反应,生成的活性醛,特别是 4-羟基壬烯醛(4-HNE),它作为自由基的第二信使和生长调节因子发挥作用。它可能来自星形胶质细胞和血管,甚至在血脑屏障(BBB)内,在脑肿瘤的情况下转化为血脑肿瘤屏障(BBTB)。4-HNE 强烈影响 BBB 的功能,因为它形成相对稳定的蛋白质加合物,从而允许脂质过氧化的持续和扩散,免疫组化研究结果证实了这一点。由于 4-HNE 可以作为正常细胞和恶性细胞重要功能的调节剂,以细胞类型和浓度依赖的方式发挥作用,因此应该进一步研究这种脂质过氧化产物的生物活性,以揭示它是致癌作用的辅助因子还是原发性脑肿瘤和转移性癌症的天然防御因子。