Using different methods we demonstrated in this article that procathepsin B possess a small, but significant catalytic activity, which is sufficient to trigger autocatalytic activation of procathepsin B. We suggest that such a model applies to all cysteine cathepsins and is of physiological relevance in various disease states including RA and OA.
COBISS.SI-ID: 22392615
Cathepsin B participates in numerous diverse cellular processes. In acquiring its activity, its proregion needs to be cleaved off. Here we demonstrate that glycosaminoglycans (GAGs), can accelerate the autocatalytic removal of the propeptide and subsequent activation of cathepsin B. Site-directed mutagenesis showed that His28, Lys39, and Arg40, located within the procathepsin B propeptide, have significant roles in the acceleration of procathepsin B activation induced by short GAGs. Therefore we proposed that GAGs may play a physiological role in the activation of procathepsin B.
COBISS.SI-ID: 20971303
In this article we critically evaluated the role of cysteine cathepsins in various disease states, including rheumatoid arthritis and osteoarthritis. In addition, we have discussed preclinical and clinical development of inhibitors of cysteine cathepsins with major emphasis on cathepsins S and K with the former being an important target in autoimmune diseases, including rheumatoid arthritis.
COBISS.SI-ID: 20500007
Cysteine cathepsins and matrix metalloproteases are considered to play important roles in the development of arthritic diseases. However, a detailed comparison between the protease levels and activities between rheumatoid arthritis samples and osteoarthritis samples has never been made. Here we report that both cysteine cathepsins B and S and matrix metalloproteases-1, -3 and -13 have been detected in patient synovial fluid samples with significantly higher levels detected in rheumatoid arthritis patients.
COBISS.SI-ID: 23546151
Genetic basis of the osteoporosis is stil unknown. Genome wide gene expression approach to study osteoblasts in osteoporotic and non-osteoporotic subjects was used. Sixteen hundred genes were differentially expressed. The results presented a list of of genes and methabolic pathways associated with the pathogenesis of osteoporosis. Differences in protein synthesis, cell proliferation and oxidateve stress response may be involved as well.
COBISS.SI-ID: 2678385