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Full-Text Articles in Medicine and Health Sciences
Reducing The Effects Of Intracellular Accumulation Of Thermolabile Collagen Ii Mutants By Increasing Their Thermostability In Cell Culture Conditions., Katarzyna Gawron, Deborah A. Jensen, Andrzej Steplewski, Andrzej Fertala
Reducing The Effects Of Intracellular Accumulation Of Thermolabile Collagen Ii Mutants By Increasing Their Thermostability In Cell Culture Conditions., Katarzyna Gawron, Deborah A. Jensen, Andrzej Steplewski, Andrzej Fertala
Department of Dermatology and Cutaneous Biology Faculty Papers
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, …
R992c (P.R1192c) Substitution In Collagen Ii Alters The Structure Of Mutant Molecules And Induces The Unfolded Protein Response., Hye Jin Chung, Deborah A. Jensen, Katarzyna Gawron, Andrzej Steplewski, Andrzej Fertala
R992c (P.R1192c) Substitution In Collagen Ii Alters The Structure Of Mutant Molecules And Induces The Unfolded Protein Response., Hye Jin Chung, Deborah A. Jensen, Katarzyna Gawron, Andrzej Steplewski, Andrzej Fertala
Department of Dermatology and Cutaneous Biology Faculty Papers
We investigated the molecular bases of spondyloepiphyseal dysplasia (SED) associated with the R992C (p.R1192C) substitution in collagen II. At the protein level, we analyzed the structure and integrity of mutant molecules, and at the cellular level, we specifically studied the effects of the presence of the R992C collagen II on the biological processes taking place in host cells. Our studies demonstrated that mutant collagen II molecules were characterized by altered electrophoretic mobility, relatively low thermostability, the presence of atypical disulfide bonds, and slow rates of secretion into the extracellular space. Analyses of cellular responses to the presence of the mutant …