• Arch Med Sci · Jan 2020

    Sulodexide up-regulates glutathione S-transferase P1 by enhancing Nrf2 expression and translocation in human umbilical vein endothelial cells injured by oxygen glucose deprivation.

    • Bożena Gabryel, Klaudia Bontor, Karolina Jarząbek, Marta Plato, Anna Pudełko, Grzegorz Machnik, and Tomasz Urbanek.
    • Department of Pharmacology, School of Medicine, Medical University of Silesia, Katowice, Poland.
    • Arch Med Sci. 2020 Jan 1; 16 (4): 957-963.

    IntroductionSulodexide (SDX) is used for the treatment of many vascular disorders due to its anticoagulant, anti-inflammatory and anti-atherosclerotic properties. However, the detailed molecular mechanism of its endothelioprotective action is still not completely understood. There is increasing evidence suggesting that antioxidant enzymes play an important role in anti-ischemic properties of SDX. We postulate that up-regulation of glutathione-S-transferase P1 (GSTP1) mediated by the transcription factor Nrf2 could be associated with the antioxidant effect of SDX on vascular endothelial cells.Material And MethodsIn the present study, we investigated whether SDX affects GSTP1 and Nrf2 in oxygen glucose deprivation (OGD) treated human umbilical vein endothelial cells (HUVECs). The cells treated with/without SDX (0.5 LRU/ml) were subjected to OGD for 1-6 h. To study the influence of SDX on the Nrf2 nucleus accumulation, the cells were incubated with 0.5 LRU/ml SDX in OGD for 1 h.ResultsWe found that after short-term OGD (1-3 h), the drug increased the expression of both GSTP1 and Nrf2 mRNA/protein in HUVECs (p < 0.05), as determined by real-time PCR and enzyme-linked immunosorbent assay (ELISA). SDX treatment also enhanced the nuclear accumulation of Nrf2 in HUVECs after 1 h of OGD (p < 0.05).ConclusionsSDX induces a rapid onset of the antioxidant response by up-regulating the expression of GSTP1 and Nrf2 in endothelial cells subjected to in vitro simulated ischemia.Copyright © 2019 Termedia & Banach.

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