The role of Sdc-4 proteoglycan in the production of NO in endothelial cells

Proteoglycans are transmembrane proteins that act as a signal transducer in communication between cells and with the extracellular matrix. In a recently published article (Lucena et al., 2018) we have shown that there is an increase in the production of reactive oxygen species and nitric oxide (NO) in mutant CHO cells for the expression of Xylosyl transferase, the enzyme responsible for the addition of glycosaminoglycans (GAGs) to the core protein. This production is associated with an increase in endothelial Nitric Oxide Synthase (NOS3) activity. In another recent publication (Cavalheiro et al., 2017), syndecan-4 (Sdc-4), a heparan sulfate proteoglycan (HSPG), was silenced in a rabbit aortic endothelial cell (RAEC). It was observed that Sdc-4 is a central mediator in focal adhesion complex and, when absent, it led to a disruption of the cytoskeleton. This feature was further explored in this present work because we were unable to cultivate the cells in shear stress conditions, most of them would always detach from the surfaces. The wild-type endothelial cells presented an activation of focal adhesion complex. We also measured an increased level of intracellular oxidation (GSSG :GSH ratio) in this present work, as it was observed in the CHO model. Another resemblance was the higher production NO in comparison to the wild-type cells, in this case, the production is maintained by the inducible NOS (NOS2). In conclusion, we account an important role for HSPG on REDOX status alterations within cells, but Sdc-4 has been shown to regulate this by specifically altering iNOS expression. (Financing agencies: FAPESP, CAPES and CNPq).