Mukhopadhyay C K, Chatterjee I B
Department of Biochemistry, University College of Science, Calcutta, India.
J Biol Chem. 1994 Dec 2;269(48):30200-5.
In this paper we demonstrate that in the absence of free metal ions, active oxygen species, generated by activated macrophages or xanthine/xanthine oxidase (XOD), carry out oxidative degradation of collagen fibrils type I in conjunction with proteases. The collagen degradation is completely prevented by ascorbate (AH2) but not by catalase. The free metal ion-independent collagen degradation is a two-step process: (i) oxidation of collagen and (ii) subsequent proteolytic cleavage of the oxidatively modified collagen. AH2 completely prevents collagen oxidation and thereby protects the collagen from subsequent proteolytic degradation. This is in contrast to free metal ion-catalyzed spontaneous fragmentation of collagen, which is accelerated by AH2 and inhibited by catalase (Kato, Y., Uchida, K., and Kawakishi, S. (1992) J. Biol. Chem. 267, 23646-23651). Studies using xanthine/XOD and model polypeptides, namely, poly-L-Pro, poly-L-hydroxyproline, poly-L-Lys, and poly(Pro-Gly-Pro) indicate that although O2-. is needed along with XOD, oxidation of model polypeptides appears to be a direct function of XOD iron, which is also stimulated by cytochrome P450.
在本文中，我们证明在没有游离金属离子的情况下，由活化的巨噬细胞或黄嘌呤/黄嘌呤氧化酶（XOD）产生的活性氧物种会与蛋白酶一起对I型胶原纤维进行氧化降解。抗坏血酸盐（AH2）可完全阻止胶原降解，但过氧化氢酶不能。与游离金属离子无关的胶原降解是一个两步过程：（i）胶原的氧化和（ii）随后对氧化修饰的胶原进行蛋白水解切割。AH2完全阻止胶原氧化，从而保护胶原免受随后的蛋白水解降解。这与游离金属离子催化的胶原自发断裂形成对比，后者被AH2加速并被过氧化氢酶抑制（加藤洋、内田健、川岸史郎（1992年）《生物化学杂志》267卷，23646 - 23651页）。使用黄嘌呤/XOD和模型多肽（即聚-L-脯氨酸、聚-L-羟脯氨酸、聚-L-赖氨酸和聚（脯氨酸-甘氨酸-脯氨酸））的研究表明，虽然O2-与XOD一起是必需的，但模型多肽的氧化似乎是XOD铁的直接作用，细胞色素P450也会刺激这种作用。
