title: The Competence of 7,8-Diacetoxy-4-Methylcoumarin and Other Polyphenolic Acetates in Mitigating the Oxidative Stress and their Role in Angiogenesis.
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.
authors.forename: Rini
authors.initials: R
authors.lastname: Joshi
authors.forename: Vishwajeet
authors.initials: V
authors.lastname: Rohil
authors.forename: Shvetambri
authors.initials: S
authors.lastname: Arora
authors.forename: Ajit
authors.initials: A
authors.lastname: Kumar
authors.forename: Sushma
authors.initials: S
authors.lastname: Manral
authors.forename: Sanjay
authors.initials: S
authors.lastname: Goel
authors.forename: Nivedita
authors.initials: N
authors.lastname: Priya
authors.forename: Prabhjot
authors.initials: P
authors.lastname: Singh
authors.forename: Prija
authors.initials: P
authors.lastname: Ponnan
authors.forename: Suvro
authors.initials: S
authors.lastname: Chatterji
authors.forename: Bilikere S
authors.initials: BS
authors.lastname: Dwarakanath
authors.forename: Daman
authors.initials: D
authors.lastname: Saluja
authors.forename: Diwan S
authors.initials: DS
authors.lastname: Rawat
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Prasad
authors.forename: Luciano
authors.initials: L
authors.lastname: Saso
authors.forename: Ekta
authors.initials: E
authors.lastname: Kohli
authors.forename: Anthony L
authors.initials: AL
authors.lastname: DePass
authors.forename: Marc E
authors.initials: ME
authors.lastname: Bracke
authors.forename: Virinder S
authors.initials: VS
authors.lastname: Parmar
authors.affiliation: V.P. Chest Institute, University of Delhi, Delhi 110 007, India. rajhgr@gmail.com.
authors.forename: Hanumantharao G
authors.initials: HG
authors.lastname: Raj
mesh_terms: D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D018384:Oxidative Stress / Q000187:drug effects*; D059808:Polyphenols / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013879:Thioredoxins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: C114369:7,8-diacetoxy-4-methylcoumarin; D003374:Coumarins; D059808:Polyphenols; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D013879:Thioredoxins