WoS İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14627/6
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Article The Effect of Vitamin D and Paricalcitol on Protein Disulfide Isomerase(Marmara Univ, Fac Pharmacy, 2024) Koksal, Muhammed Murat; Sekerler, Turgut; Sener, AzizeProtein disulfide isomerase (PDI), a multifunctional protein plays an important role as oxidoreductase, isomerase and chaperone in the cell. Prior studies have identified PDI is highly expressed in many different cancer types and presented as a new potential target for cancer treatment. Here, we investigated vitamin D and its analogue paricalcitol in silico interaction of the human PDI and inhibition of PDI reductase activity in vitro. We observed a non-covalent mechanism where the main skeleton of the vitamin D3 and paricalcitol structure is located at the hydrophobic site in the b' domain of PDI and forms a hydrogen bond with a residue (His138) in this domain. They also form multiple weak hydrophobic interactions with various chemical groups of the b' subunit. For the first time, we demonstrate that 1,25dihydroxyvitamin D3 (1 alpha,25(OH)2 vitamin D3) and paricalcitol inhibit the PDI reductase activity in vitro and their IC50 values are 20.79 +/- 1.43 nmol/L and 32.82 +/- 3.15 nmol/L respectively. The two compounds can also block the denitrosation activity of PDI.Article Citation - WoS: 5Citation - Scopus: 5Paricalcitol Protects Against Hydrogen Peroxide-Induced Injury in Endothelial Cells Through Suppression of Apoptosis(Frontiers Media Sa, 2023) Koksal, Muhammet Murat; Sekerler, Turgut; Cevik, Ozge; Sener, AzizeThe vascular endothelium is one of the main targets of oxidative stress which plays an important role in the pathophysiology of vascular damage. Recent studies show that vitamin D can positively regulate endothelial functions in various chronic diseases and in cases of increased oxidative stress. In our study, we investigated the restorative and protective potentials of paricalcitol which is frequently used in patients with chronic renal failure, a vitamin D analogue, in human umbilical vein endothelial cells (HUVEC) before and after H2O2-induced oxidative stress. Paricalcitol treatment after the oxidative stress induced by H2O2 increased cell viability in endothelial cells depending on the dose that was used. While paricalcitol (500 nM) decreased caspase-3 activity and mitochondrial membrane potential loss, it increased nitric oxide (NO) production and reduced glutathione (GSH) levels. Paricalcitol treatment before oxidative stress increased cell viability. It increased NO production and mitochondrial membrane potential while significantly reducing caspase-3 activity. While paricalcitol caused a significant inhibition of protein disulfide isomerase (PDI) reductase activity in healthy endothelial cells, it did not cause a significant change on the PDI reductase activity under oxidative stress conditions. Present study showed that paricalcitol has restorative and protective effects on endothelial cells against oxidative injury, but these effects occur at high concentrations of paricalcitol.