Reducing the effects of intracellular accumulation of thermolabile collagen II mutants by increasing their thermostability in cell culture conditions.
Reducing the effects of intracellular accumulation of thermolabile collagen II mutants by increasing their thermostability in cell culture conditions.
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DOI：
10.1016/j.bbrc.2010.04.056
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发表时间：
2010-05-28
影响因子：
3.1
通讯作者：
Fertala, Andrzej
中科院分区：
文献类型：
--
作者：
Gawron, Katarzyna;Jensen, Deborah A.;Steplewski, Andrzej;Fertala, Andrzej
胶原蛋白II的突变与脊椎骨骺发育不良有关，脊椎骨骺发育不良是一组遗传性疾病，其共同特征包括骨骼生长异常。胶原II突变影响软骨组织的机制是复杂的，包括细胞内和细胞外过程。这些机制之一涉及由错误折叠的胶原蛋白II突变体的过度积累引起的细胞应激。我们研究了稳定不耐热的R789 C和R992 C胶原II突变体的结构是否会改善它们从细胞中的分泌，从而减少细胞应激和凋亡。使用甘油和三甲基胺N-氧化物（TMAO），增加胶原蛋白三螺旋的热稳定性的化学物质，我们证明了这些化合物作为分子伴侣，稳定R789 C和R992 C突变体，加速它们的分泌，并提高细胞存活率。我们的研究提供了一个科学依据，考虑错误折叠的三螺旋胶原蛋白突变体的目标，以减少其过度的细胞内积累所造成的有害影响。
Mutations in collagen II are associated with spondyloepiphyseal dysplasia, a group of heritable diseases whose common features include aberrations of skeletal growth. The mechanisms through which mutations in collagen II affect the cartilaginous tissues are complex and include both intracellular and extracellular processes. One of those mechanisms involves cellular stress caused by excessive accumulation of misfolded collagen II mutants. We investigated whether stabilizing the structure of thermolabile R789C and R992C collagen II mutants would improve their secretion from cells, thereby reducing cellular stress and apoptosis. Employing glycerol and trimethylamine N-oxide (TMAO), chemicals that increase the thermostability of collagen triple helices, we demonstrated that those compounds function as chaperones and stabilize the R789C and R992C mutants, accelerate their secretion, and improve cell survival. Our study provides a scientific basis for considering misfolded triple helices of collagen mutants a target for reducing the deleterious effects caused by their excessive intracellular accumulation.
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影响因子：
6.2
作者：
Donahue, LR;Chang, B;Davisson, MT
通讯作者：
Davisson, MT
影响因子：
4.1
作者：
RUSSELL, AE
通讯作者：
RUSSELL, AE
影响因子：
3.9
作者：
Kumar, R;Serrette, JM;Thompson, EB
通讯作者：
Thompson, EB
DOI：
10.1111/j.1749-6632.2003.tb03217.x
发表时间：
2003-01-01
期刊：
TISSUE REMODELING
影响因子：
--
作者：
Gustafsson, E;Aszódi, A;Fässler, R
通讯作者：
Fässler, R
DOI：
10.1073/pnas.070050097
发表时间：
2000-04-11
影响因子：
11.1
作者：
Beck, K;Chan, VC;Brodsky, B
通讯作者：
Brodsky, B