New multienzymatic complex formed between human cathepsin D and snake venom phospholipase A2

Background Cathepsin D (CatD) is a lysosomal proteolytic enzyme expressed in almost all tissues and organs. This protease is a multifunctional enzyme responsible for essential biological processes such as cell cycle regulation, differentiation, migration, tissue remodeling, neuronal growth, ovulation, and apoptosis. The overexpression and hypersecretion of CatD have been correlated with cancer aggressiveness and tumor progression, stimulating cancer cell proliferation, fibroblast growth, and angiogenesis. In addition, some studies report its participation in neurodegenerative diseases and inflammatory processes. In this regard, the search for new inhibitors from natural products could be an alternative against the harmful effects of this enzyme. Methods An investigation was carried out to analyze CatD interaction with snake venom toxins in an attempt to find inhibitory molecules. Interestingly, human CatD shows the ability to bind strongly to snake venom phospholipases A2 (svPLA2), forming a stable muti-enzymatic complex that maintains the catalytic activity of both CatD and PLA2. In addition, this complex remains active even under exposure to the specific inhibitor pepstatin A. Furthermore, the complex formation between CatD and svPLA2 was evidenced by surface plasmon resonance (SPR), two-dimensional electrophoresis, enzymatic assays, and extensive molecular docking and dynamics techniques. Conclusion The present study suggests the versatility of human CatD and svPLA2, showing that these enzymes can form a fully functional new enzymatic complex.

Estudo experimental dos efeitos da radiaçäo laser de baixa energia na reneraçäo osteocartilagínea em joelhos de coelhos: aspectos histológicos / Experimental study of low energy laser radiation to regenerate osteocartilage lesions in rabbit knees: histological aspects

Os autores realizaram estudo experimental em coelhos submetendo à irradiaçäo laser de baixa energia lesöes produzidas em cartilagem articular e osso subcondral dos joelhos, com o objetivo de avaliar os possíveis efeitos histológicos da mesma na regeneraçäo cartilaginosa e óssea. Os animais foram sacrificados aos 15, 30, 45 e 60 dias de pós-operatório, sendo realizado nessa oportunidade estudo histológico. Os resultados mostraram que nao houve qualquer reaçäo de regeneraçäo articular, que aos 60 dias de evoluçäo foi totalmente substituída por tecido conjuntivo de natureza cicatricial. Quanto à lesäo do osso subcondral, observou-se evoluçäo com formaçäo de calo ósseo típico, que, entretanto, demonstrou velocidade de aparecimento mais rápida e com maior intensidade nos espécimes tratados com irradiaçäo laser em relaçäo aos näo tratados.