1. The Competence of 7,8-Diacetoxy-4-Methylcoumarin and Other Polyphenolic Acetates in Mitigating the Oxidative Stress and their Role in Angiogenesis.
- Author
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Joshi R, Rohil V, Arora S, Kumar A, Manral S, Goel S, Priya N, Singh P, Ponnan P, Chatterji S, Dwarakanath BS, Saluja D, Rawat DS, Prasad AK, Saso L, Kohli E, DePass AL, Bracke ME, Parmar VS, and Raj HG
- Subjects
- Coumarins chemistry, Enzyme-Linked Immunosorbent Assay, Humans, Polyphenols chemistry, Reactive Oxygen Species antagonists & inhibitors, Reactive Oxygen Species metabolism, Real-Time Polymerase Chain Reaction, Thioredoxins biosynthesis, Thioredoxins genetics, Thioredoxins metabolism, Vascular Endothelial Growth Factor A genetics, Coumarins pharmacology, Neovascularization, Pathologic drug therapy, Oxidative Stress drug effects, Polyphenols pharmacology
- Abstract
The potential role of polyphenolic acetate (PA) in causing diverse biological and pharmacological actions has been well studied in our laboratory. Our investigations, for the first time, established the role of calreticulin transacetylase (CRTAase) in catalyzing the acetylation of nitric oxide synthase (NOS) by Pas leading to robust activation of NOS. 7, 8- Diacetoxy-4-methylcoumarin (DAMC) and other acetoxycoumarins augmented the expression of thioredoxin (TRX) and vascular endothelial growth factor (VEGF) in human peripheral blood mononuclear cells (PBMCs). These findings substantiated our earlier observations that DAMC was a superb inducer of angiogenesis. The enhanced expression of thioredoxin reductase (TRXR) and diminished expression of thioredoxin interacting protein (TRXIP) leading to increased expression and activity of TRX in PBMCs due to the action of DAMC was revealed by real time RT-PCR analysis. The possible activation of TRX due to acetylation was confirmed by the fact that TRX activity of PBMCs was enhanced by various acetoxycoumarins in tune with their affinities to CRTAase as substrates. DAMC caused enhanced production of NO by way of acetylation of NOS as mentioned above and thereby acted as an inducer of VEGF. Real time RT-PCR and VEGF ELISA results also revealed the overexpression of TRX. DAMC and other PAs were found to reduce the oxidative stress in cells as proved by significant reduction of intracellular ROS levels. Thus, the crucial role of TRX in DAMC-induced angiogenesis with the involvement of VEGF was established.
- Published
- 2015