Lukasheva E V, Ribakova Yu S, Fedorova T N, Makletsova M G, Arinbasarova A Yu, Medentzev A G, Berezov T T
Biomed Khim. 2015 Jan-Feb;61(1):99-104. doi: 10.18097/pbmc20156101099.
L-Amino acid oxidases (L-ААО, EC 1.4.3.2) comprise a group of flavoproteins, catalyzing oxidative deamination of L-alpha amino acids to the corresponding alpha-keto acids, NH3 and Н2О2. In most cases these enzymes present homodimeric molecules with a molecular mass of 100-150 kDa, which were shown to possess antiviral, antifungal and antitumor activity. L-lysine alpha-oxidase (LO) holds an outstanding place among this group of enzymes and its biological role may differ significantly from the other L-AAO, because it cleaves an essential amino acid - L-lysine without significant action on the other amino acids. Although much research has examined LO effects in the organism, the molecular basis of these effects is yet to be identified. To fill this gap, the present work addressed one of hypothetical mechanisms of LO biological action using the enzyme from Trichoderma cf. aureoviride Rifai ВКМF-4268D and rat pheochromocytoma PC-12 as a model cell line. Using flow cytometry a dose-dependent cytotoxicity of LO was shown. The significant growth of intracellular reactive oxygen species levels, detected by 2,7-dichlorodihydrofluorescein assay, implies generation of peroxide as one of the molecular mechanisms of LO cytotoxic action, although this does not rule out other probable ways of LO action in the organizm.
L-氨基酸氧化酶（L-ААО，EC 1.4.3.2）是一组黄素蛋白，催化L-α氨基酸氧化脱氨生成相应的α-酮酸、NH₃和H₂O₂。在大多数情况下，这些酶呈现分子量为100 - 150 kDa的同二聚体分子，已证明它们具有抗病毒、抗真菌和抗肿瘤活性。L-赖氨酸α-氧化酶（LO）在这组酶中占有突出地位，其生物学作用可能与其他L-AAO有显著差异，因为它能裂解必需氨基酸——L-赖氨酸，而对其他氨基酸没有明显作用。尽管已有许多研究探讨了LO在生物体中的作用，但这些作用的分子基础尚未确定。为填补这一空白，本研究以来自哈茨木霉cf. 黄绿木霉Rifai ВКМF - 4268D的酶和大鼠嗜铬细胞瘤PC - 12作为模型细胞系，探讨了LO生物学作用的一种假设机制。通过流式细胞术显示了LO的剂量依赖性细胞毒性。用2,7 - 二氯二氢荧光素测定法检测到细胞内活性氧水平显著升高，这意味着过氧化物的产生是LO细胞毒性作用的分子机制之一，尽管这并不排除LO在生物体中其他可能的作用方式。
