The Competence of 7,8-Diacetoxy-4-Methylcoumarin and Other Polyphenolic Acetates in Mitigating the Oxidative Stress and their Role in Angiogenesis

Title:The Competence of 7,8-Diacetoxy-4-Methylcoumarin and Other Polyphenolic Acetates in Mitigating the Oxidative Stress and their Role in Angiogenesis

Volume: 15 Issue: 2

Author(s): Bilikere S. Dwarakanath, Hanumantharao G. Raj, Virinder S. Parmar, Marc E. Bracke, Anthony L. DePass, Ekta Kohli, Luciano Saso, Ashok K. Prasad, Diwan S. Rawat, Daman Saluja, Rini Joshi, Suvro Chatterji, Prija Ponnan, Prabhjoth Singh, Nivedita Priya, Sanjay Goel, Ajit Kumar, Sushma Manral, Shvetambri Arora and Vishwajeet Rohil

Affiliation:

Keywords: Calreticulin transacetylase, Vascular endothelial growth factor, Thioredoxin, Nitric oxide synthase.

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 variousacetoxycoumarins 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 DAMCinduced angiogenesis with the involvement of VEGF was established.

Cite this article as:

Dwarakanath S. Bilikere, Raj G. Hanumantharao, Parmar S. Virinder, Bracke E. Marc, DePass L. Anthony, Kohli Ekta, Saso Luciano, Prasad K. Ashok, Rawat S. Diwan, Saluja Daman, Joshi Rini, Chatterji Suvro, Ponnan Prija, Singh Prabhjoth, Priya Nivedita, Goel Sanjay, Kumar Ajit, Manral Sushma, Arora Shvetambri and Rohil Vishwajeet, The Competence of 7,8-Diacetoxy-4-Methylcoumarin and Other Polyphenolic Acetates in Mitigating the Oxidative Stress and their Role in Angiogenesis, Current Topics in Medicinal Chemistry 2015; 15 (2) . https://dx.doi.org/10.2174/1568026615666141209162446