Galicka A, Wolczyñski S, Anchim T, Surazyñski A, Lesniewicz R, Palka J
Department of General and Organic Chemistry, Medical Academy of Bialystok, Poland.
Eur J Biochem. 2001 Apr;268(7):2172-8. doi: 10.1046/j.1432-1327.2001.02099.x.
We have studied the structure and metabolism of type I procollagen in a case of perinatal lethal osteogenesis imperfecta (OI) type II. Cultured skin fibroblasts from the proband synthesized both normal and abnormal forms of type I procollagen. Some abnormal, overmodified molecules were secreted by OI cells, although less efficiently than normal molecules from control cells. The OI fibroblasts accumulated large amounts of abnormal proalpha1(I) and proalpha2(I) chains intracellularly. The extracellular collagenolytic activity was decreased compared to control cells. Furthermore, OI cells produced less type I procollagen and demonstrated lower capacity to synthesize DNA than control cells. We have found that in contrast to prolinase activity, the activity of prolidase (an enzyme essential for collagen synthesis and cell growth) is also significantly reduced in OI cells. No differences were found in the amount of the enzyme protein recovered from both the OI and control cells. However, we found that expressions of beta1 integrin and insulin-like growth factor-I receptor (receptors known to play an important role in up regulation of prolidase activity) were decreased in OI cells compared to control cells. The decrease in prolidase activity may provide an important mechanism of altered cell growth and collagen metabolism involved in producing the perinatal lethal form of the OI phenotype.
我们研究了一例围产期致死性II型成骨不全症（OI）中I型前胶原的结构和代谢。先证者的培养皮肤成纤维细胞合成了正常和异常形式的I型前胶原。一些异常的、过度修饰的分子由OI细胞分泌，尽管效率低于对照细胞分泌的正常分子。OI成纤维细胞在细胞内积累了大量异常的前α1（I）和前α2（I）链。与对照细胞相比，细胞外胶原olytic活性降低。此外，OI细胞产生的I型前胶原较少，且与对照细胞相比，其合成DNA的能力较低。我们发现，与脯氨酰肽酶活性相反，脯氨酰二肽酶（一种对胶原合成和细胞生长至关重要的酶）的活性在OI细胞中也显著降低。从OI细胞和对照细胞中回收的酶蛋白量没有差异。然而，我们发现与对照细胞相比，OI细胞中β1整合素和胰岛素样生长因子-I受体（已知在脯氨酰二肽酶活性上调中起重要作用的受体）的表达降低。脯氨酰二肽酶活性的降低可能是导致OI表型围产期致死形式的细胞生长和胶原代谢改变的重要机制。
