[Type I and IV collagenases and their endogenous regulators in immortalized and transformed fibroblasts].

To elucidate the role of matrix metalloproteinases (MMP) in carcinogenesis, the expression of collagenases of types I (MMP-I) and IV (MMP-2 and MMP-9) as well as the behaviour of urokinase-like plasminogen activator (uPA) and of tissue MMP inhibitors (TIMP) in immortalized (IF) and transformed (TF) fibroblasts were investigated. The study was carried out using embryo rat fibroblasts, sequentially immortalized with the LT gene of human papilloma virus and transformed with the E7 gene of human papilloma virus (HPV-16). As control was used the primary fibroblast (PF) culture of Fisher rats.

[Expression of cathepsins D and L during neoplastic transformation of fibroblasts].

Study of the expression of the aspartyl cathepsin D-like and cysteine cathepsin L-like proteinases was carried out on a model system of rat embryo fibroblasts. The model system employed makes it possible to distinguish two discrete successive stages of transformation in vitro: immortalization and tumorigenic transformation. The dynamics of expression and subcellular distribution of proteinases throughout the transformation process was followed.

[Interaction of collagenases with certain peptide substrates and inhibitors].

Interactions of collagenases I and II (clostridiopeptidases) from Clostridium histolyticum with hexapeptide substrates in which some L-proline residues are replaced by their D-analogues, as well as with the tripeptide chloromethyl ketone Z-Gly-Pro-Gly-CH2Cl were studied. A role of stereochemistry of the amino acid residues in the substrate was established and differences between the collagenases, with regard to their specific requirements to substrates, were revealed. The tripeptide chloromethyl ketone is shown to be a specific collagenase inhibitor modifying at the substrate-binding site in the active centre of these enzymes, most likely lysine residues.

[Study on the effect of some group-specific agents on clostridiopeptidase].

The interaction of clostridiopeptidase of Clostridium histolyticum with EDC, TNM and MA, the specific reagents for COOH-groups, tyrosine and lysine residues was studied. It was shown that at pH 6.0 EDC inactivates the enzyme.