About Heparanase / HPSE:
Also known or referred to as HPSE, heparanase is an enzyme. This enzyme will act at the extracellular matrix as well as the cell surface to trigger the degradation of polymeric heparan sulfate molecules. It causes them to become shorter chains that are oligosaccharides.
There are crystal structures for both the mature heparanase as well as the proheparanese. Both seem to show that the linker peptide actually causes a helical domain. This domain blocks the heparan sulfate molecules from having an interaction with heparanase. It also reveals a cleft that exists on the surface of the enzyme which does include the heparanase active site.
The protein is typically synthesized in a mechanism which occurs in the 65 kDa proheparanase form which is inactive. This exists in the Golgi apparatus and is then moved to the lysosomes/endosomes. Here it awaits transport to the surface of the cell. In the lysosome, the proteolytical process transforms it into an active form. It results in three products being produced. This includes a linked peptide, a 50 kDa proheparanase fragment and an 8 kDa proheparanese fragment. The two later fragments form a heterodimer. This is the active heparanase molecule.
The interactions of heparanase have led to it being involved in a wide range of clinical studies. When the endothelial cell layer which lines the surface of the blood levels is penetrated it plays a crucial process that is involved in the tumor meastasese which is blood borne. Studies have shown that the heparan sulfate proteoglycans which is a key part of this layer are involved in the increase in heparanase activity throughout the cell lines. As such, it is considered to be a possible target for therapies directly related to treating cancer.
Furthermore, heparanase has also been explored for promoting arterial thrombosis as well as stent thrombosis. This is due to the cleavage for the anti-coagulant heparan sulfate proteoglycans.
Further studies have shown that heparanase does interact with Resistin and actually causes activity of this chemical to cease. This stops the bioactive of resistance that is typically present in the standard bioassay during the monocytic human leukemia cell line. Instead, it changes into adherent foam cells that are macrophage-like. As such, researchers have suggested that the new complex causes a stimulatory impact which is present in a variety of conditions deemed inflammatory.
This enzyme does have endoglycosidase activity. During this activity, it cleaves polymeric heparan sulfate molecules. This occurs at sites which are within the polymeric chain. Through ocular surface physiology, this can function as an on or off switch for the prosecretory mitogen lacritin.
Here lacrtin is used binding the surface of the sell heparan sulfate proteoglycan syndecan-1 through the presence of active heparanase. The heparan sulfate is either partially or fully cleaved which then exposes a binding site that exists in the N-terminal for the 50 amino acids that exist within syndecan-1.