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Dias, AAS. Role of Protein disulfide isomerase in vascular reactivity of Angiotensin II and Noradrenaline: Involvement of NADPH oxidase [Ph. D thesis (Pharmacology)]. Sao Paulo: Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo: 2011. Reactive oxygen species (ROS) are intermediates of signaling pathways which regulates cellular events relevant for the vascular smooth cells function as migration, proliferation and contraction.The NADPH oxidase is the main enzimatic source of ROS with the signaling purpose on the cardiovascular system. We previously demonstrated that the protein disulfide isomerase (PDI), a redox chaperone of endoplasmic reticulum, is able to modulate the ROS generation and the activation of signaling redox ways dependent of Ang II. Although the recent advances in the understanding of mechanisms that regulate the interaction of PDI and NADPH oxidase, the role of this chaperone in the biological effects related to ROS, as vascular contraction, are not well clarified. The inhibition of the contractile response by DTNB, an oxidant thiol, suggest the involvement of proteins containing thiols as the PDI and NADPH oxidase in the contraction of isolated aortas stimulated with Ang II. These results were confirmed by experiments that demonstrated the PDI expression in Wistar rats vascular layers and a co-localization of this protein with the NOX-1 isoform. PDI inhibition decreased ROS generation and the Ang II and NOR – induced vascular reactivity endothelium independent. The investigation of involved mechanisms suggest that one PDI role is the calcium mobilization from the intracellular storage by NADPH oxidase way. MAPkinases activation contributed to increase de intracellualar calcium in stimulated aortas with AngII and NOR. However, the PDI inhibition reduced the ERK 1/2 fosforilation in AngIIstimulated aorta, but not with NOR. Analyses of all of our results suggests that dependent and independent redox mechanims were involved in the regulation of contractile response to Ang II and NOR by PDI.

Papel da proteina dissulfeto isomerase na reatividade vascular à angiotensina II e noradrenalina: envolvimento da NADPH oxidase.