Molecular characterization and expression analysis of cathepsin C in the marine crab Charybdis japonica (A. Milne-Edwards, 1861) (Decapoda, Brachyura, Portunidae)

Cathepsin C is a crucial lysosomal cysteine proteinase that takes part in protein degradation and proenzyme activation. In this study, cDNA of cathepsin C in Charybdis japonica (A. Milne-Edwards, 1861) (designated as Cj-cath C) was cloned and characterized. The results showed that the open reading frame (ORF) of Cj-cath C was 1356 bp and encoded a protein of 451 amino acids. Cj-cath C contained two catalytic residues, a Cathepsin C exclusion domain and a Peptidase_C1 domain. The Cj-cath C was widely expressed in all tissues, with highest expression in hepatopancreas and heart. The transcript levels of Cj-cath C in the hepatopancreas and haemolymph were up-regulated after stimulation by Vibrio anguillarum Bergeman, 1909 and reached a peak value at 6 h post-infection, followed by a gradual decrease. These observations indicate that Cj-cath C might be a constitutive and inducible acute-phase protein that is involved in the immune defense of C. japonica.

Metalloprotease meprin β is activated by transmembrane serine protease matriptase-2 at the cell surface thereby enhancing APP shedding

Metalloprotease meprin β is a sheddase of transmembrane proteins. We identified serine protease matriptase-2 (MT2) as a specific activator of meprin β at the cell surface. This provides mechanistic insight for the regulation of meprin β activity and demonstrates clear differences in proenzyme activation.

Matrix Metalloproteinase-9 and Haemozoin: Wedding Rings for Human Host andPlasmodium falciparumParasite in Complicated Malaria

It is generally accepted that the combination of bothPlasmodium falciparumparasite and human host factors is involved in the pathogenesis of complicated severe malaria, including cerebral malaria (CM). Among parasite products, the malarial pigment haemozoin (HZ) has been shown to impair the functions of mononuclear and endothelial cells. Different CM models were associated with enhanced levels of matrix metalloproteinases (MMPs), a family of proteolytic enzymes able to disrupt subendothelial basement membrane and tight junctions and shed, activate, or inactivate cytokines, chemokines, and other MMPs through cleavage from their precursors. Among MMPs, a good candidate for targeted therapy might be MMP-9, whose mRNA and protein expression enhancement as well as direct proenzyme activation by HZ have been recently investigated in a series of studies by our group and others. In the present paper the role of HZ and MMP-9 in complicated malaria, as well as their interactions, will be discussed.