Giannini Cinzia, De Caro Liberato, Terzi Alberta, Fusaro Luca, Altamura Davide, Diaz Ana, Lassandro Rocco, Boccafoschi Francesca, Bunk Oliver
Institute of Crystallography, National Research Council, Bari, 70126, Italy.
Department of Health Sciences, University of Piemonte Orientale, Novara, Italy.
IUCrJ. 2021 Jun 3;8(Pt 4):621-632. doi: 10.1107/S2052252521005054. eCollection 2021 Jul 1.
Diseases like widespread diabetes or rare galactosemia may lead to high sugar concentrations in the human body, thereby promoting the formation of glycoconjugates. Glycation of collagen, the formation of glucose bridges, is nonenzymatic and therefore cannot be prevented in any other way than keeping the sugar level low. It relates to secondary diseases, abundantly occurring in aging populations and diabetics. However, little is known about the effects of glycation of collagen on the molecular level. We studied the effect of glycation, with d-glucose and d-galactose as well as d-ribose, on the structure of type 1 collagen by preparing decellularized matrices of bovine pericardia soaked in different sugar solutions, at increasing concentrations (0, 2.5, 5, 10, 20 and 40 mg ml), and incubated at 37°C for 3, 14, 30 and 90 days. The tissue samples were analyzed with small- and wide-angle X-ray scattering in scanning mode. We found that glucose and galactose produce similar changes in collagen, they mainly affect the lateral packing between macromolecules. However, ribose is much faster in glycation, provoking a larger effect on the lateral packing, but also seems to cause qualitatively different effects on the collagen structure.
像广泛流行的糖尿病或罕见的半乳糖血症等疾病可能会导致人体血糖浓度升高,从而促进糖缀合物的形成。胶原蛋白的糖基化,即葡萄糖桥的形成,是非酶促反应,因此除了保持低血糖水平外,无法以其他方式预防。它与在老年人群和糖尿病患者中大量出现的继发性疾病有关。然而,关于胶原蛋白糖基化在分子水平上的影响,人们了解得很少。我们通过制备浸泡在不同浓度(0、2.5、5、10、20和40 mg ml)糖溶液中的牛心包脱细胞基质,研究了d-葡萄糖、d-半乳糖以及d-核糖糖基化对I型胶原蛋白结构的影响,并在37°C下孵育3、14、30和90天。用扫描模式下的小角和广角X射线散射对组织样本进行分析。我们发现葡萄糖和半乳糖在胶原蛋白中产生类似的变化,它们主要影响大分子之间的侧向堆积。然而,核糖的糖基化速度要快得多,对侧向堆积产生更大的影响,但似乎也对胶原蛋白结构产生了质的不同的影响。