This review paper, published in one of the best journals in the field, is an acknowledgement for whole group working on proteases in Ljubljana. In the paper we demonstrated the physiological and pathological functions of cysteine cathepsins and their inhibitors, and suggested further research goals and directions. We reported our achievements, focusing on the role of cathepsins B and L in the degradation of proteins of the extracellular matrix and basal membrane, which is a key molecular event in processes of tumour invasion, angiogenesis and metastasis.
Obesity is a serious chronic disease, which causes complications such as diabetes, hypertension, and osteoarthritis. Inhibition of lipid metabolism is an important pharmaceutical approach for treatment of this disease. Pancreatic phosphatase was identified as a promising target. In this paper the selection of hexapeptides obtained from a phage library as potential inhibitors of pancreatic phosphatase is demonstrated.
This paper results from the co-operation with Dr. Bogyo from Stanford University . It is known that the parasite P. falciparum escapes from host erythrocytes by a process controlled by proteases, although it was not known which protease is involved. Using a new method we selected, from 1200 inhibitors of serine and cysteine proteases, those that are capable of preventing the destruction of erythrocytes by P. falciparum. In this way we found that the most important proteases in this process are the subtilisin serine protease PfSU B1 and the cysteine protease dipeptidyl peptidase 3 (DPAP3).
To investigate the role of cathepsin X in the migration of T lymphocytes, Jurkat T cells were stably transfected with a pcDNA3 expression vector containing cathepsin X cDNA. The cathepsin-X-overexpressing T lymphocytes exhibited polarised migration-associated morphology, enhanced migration on 2D and 3D models and increased homotypic aggregation. We propose that cathepsin X causes cytoskeletal rearrangements and stimulates migration of T lymphocytes by modulating the activity of the beta2 integrin receptor LFA-1.
The aim was to investigate the protective role of fullerenol C60(OH)24 on doxorubicin-induced liver toxicity in vivo and in vitro . The rats with all with breast cancer were treated with doxorubicin, doxorubicin/fullerenol and fullerenol, respectively. Results showed that treatment with doxorubicin alone caused significant changes in the serum levels of ALT, AST, LDH and alpha-HBDH, and MDA, GSH, GSH-Px, TAS, GR, CAT and SOD in the liver . These effects were significantly reduced for all investigated parameters by pre-treatment with fullerenol and confirmed on HepG2 and Caco-2 cells.