Mizutari K, Ono T, Ikeda K, Kayashima K, Horiuchi S
Department of Dermatology, Kumamoto University School of Medicine, Honjo, Japan.
J Invest Dermatol. 1997 May;108(5):797-802. doi: 10.1111/1523-1747.ep12292244.
Long-term incubation of proteins with glucose leads to the formation of advanced glycation end products (AGEs), which are characterized by fluorescence, brown color, and cross-linking. Formation of AGEs in vitro requires oxygen and is dependent on transition metal-catalyzed oxidation of glucose or Amadori products. AGEs are thought to be involved in aging and age-enhanced diseases such as diabetic complications, atherosclerosis, dialysis-related amyloidosis, and Alzheimer's disease. Chronic exposure of the skin to sunlight induces hyperplasia of the elastic tissue in the upper dermis known as actinic elastosis. Herein we used a monoclonal anti-AGE antibody (6D12) whose epitope is N(epsilon)-(carboxymethyl)lysine (CML), one of the glycoxidation products of AGEs, and demonstrated that the lesions of actinic elastosis were modified by CML. Further immunohistochemical and immunoelectron microscopic examination with 6D12 demonstrated CML accumulates predominantly in elastic fibers especially in the amorphous electron-dense materials corresponding to photo-induced degenerated area rather than the electron-lucent region. Immunochemical analyses with enzyme-linked immunosorbent assay (ELISA) of elastase-soluble fractions demonstrated that the CML levels of the sun-exposed area were significantly higher than those of the sun-unexposed area. We conclude that ultraviolet-induced oxidation may accelerate CML formation in actinic elastosis of photoaged skin.
蛋白质与葡萄糖长期孵育会导致晚期糖基化终产物（AGEs）的形成，其特征为具有荧光、呈棕色且能发生交联。体外AGEs的形成需要氧气，并且依赖于过渡金属催化的葡萄糖或阿马多里产物的氧化。AGEs被认为与衰老以及与年龄相关的疾病有关，如糖尿病并发症、动脉粥样硬化、透析相关淀粉样变性和阿尔茨海默病。皮肤长期暴露于阳光下会导致真皮上层弹性组织增生，即光化性弹力纤维病。在此，我们使用了一种单克隆抗AGE抗体（6D12），其表位是N（ε）-（羧甲基）赖氨酸（CML），这是AGEs的糖氧化产物之一，并证明光化性弹力纤维病的病变可被CML修饰。进一步用6D12进行免疫组织化学和免疫电子显微镜检查表明，CML主要积聚在弹性纤维中，尤其是在与光诱导退变区域相对应的无定形电子致密物质中，而非电子透亮区域。用酶联免疫吸附测定（ELISA）对弹性蛋白酶可溶部分进行免疫化学分析表明，暴露于阳光下区域的CML水平显著高于未暴露于阳光下的区域。我们得出结论，紫外线诱导的氧化可能会加速光老化皮肤光化性弹力纤维病中CML的形成。
