Levene C I, Ockleford C D, Barber C L
Virchows Arch B Cell Pathol. 1977 Apr 15;23(4):325-38. doi: 10.1007/BF02889141.
Earlier biochemical investigations of cultured 3T6 fibroblasts have shown that ascorbate deficiency has no effect on the synthesis of collagen protein quantitatively but does produce inhibition of the critical post-translational hydroxylation of collagen essential for normal fibrogenesis and of formation of hydroxylysine-derived cross-links. This ultrastructural study on the same 3T6 fibroblast system demonstrates that ascorbate deficiency does not affect the cell morphology, particularly that of the protein synthetic or secretory apparatus, but does prevent the deposition of typical 640A degrees banded collagen fibres; instead, finer, unbanded fibrils--presumably collagenous--are deposited extracellularly. This confirms the earlier biochemical findings as wll as presenting a new finding--the inability of ascorbate-deficient cells to lay down normal collagen fibrils; possible mechanisms are considered in terms of the known biochemical lesions. The tissue culture findings are also compared with those observed in vivo in the scorbutic guinea-pig, where other workers have reported biochemical and ultrastructural evidence that collagen synthesis is inhibited. The apparently paradoxical observations in the two systems are considered; we conclude that the tissue culture system demonstrates the primary collagenous lesion which is perhaps obscured in vivo by secondary effects--nevertheless the two approaches are complementary.
早期对培养的3T6成纤维细胞进行的生化研究表明，抗坏血酸缺乏在数量上对胶原蛋白的合成没有影响，但确实会抑制胶原蛋白在翻译后进行的关键羟基化过程，而这种羟基化对于正常的纤维生成以及羟赖氨酸衍生的交联形成至关重要。对同一3T6成纤维细胞系统进行的这项超微结构研究表明，抗坏血酸缺乏并不影响细胞形态，特别是蛋白质合成或分泌装置的形态，但确实会阻止典型的640埃带状胶原纤维的沉积；相反，更细的、无带状的原纤维（大概是胶原性的）会在细胞外沉积。这证实了早期的生化研究结果，同时也呈现了一个新发现——抗坏血酸缺乏的细胞无法形成正常的胶原纤维；根据已知的生化损伤情况对可能的机制进行了探讨。还将组织培养的结果与在患坏血病的豚鼠体内观察到的结果进行了比较，其他研究人员在豚鼠体内报告了胶原合成受到抑制的生化和超微结构证据。对这两个系统中明显矛盾的观察结果进行了探讨；我们得出结论，组织培养系统显示出原发性胶原损伤，这种损伤在体内可能被继发性效应所掩盖——尽管如此，这两种方法是互补的。
