Promoter sequence interaction and structure based multi-targeted (redox regulatory genes) molecular docking analysis of vitamin E and curcumin in T4 induced oxidative stress model using H9C2 cardiac cell line. Issue 22 (12th December 2022)

• Record Type: Journal Article
• Authors: Mishra, Pallavi; Tandon, Gitanjali; Kumar, Manoj; Paital, Biswaranjan; Swain, Shasanka Sekhar; Kumar, Sunil; Samanta, Luna
• Is Part Of: Journal of biomolecular structure & dynamics. Volume 40:Issue 22(2022)
• Page Start: 12316
• Page End: 12335
• Publication Date: 2022-12-12
• Subjects: Promoter ligand interaction -- curcumin -- vitamin E -- structural binding -- NRF-2/KEAP 1 activation; Biomolecules -- Periodicals; Molecular structure -- Periodicals; Molecular Biology -- Periodicals; Biomechanics -- Periodicals; 572
• DOI: 10.1080/07391102.2021.1970624
• Languages: English
• ISSNs: 0739-1102

Abstract

Abstract: A positive association between oxidative stress and hyper-thyroid conditions is well established. Vitamin E (VIT-E) and curcumin (CRM) are considered as potent antioxidant small molecules. Nuclear factor erythroid 2–related factor 2(NRF-2) is known to bind with antioxidant response element and subsequently activate expression of antioxidant enzymes. However, the activation of NRF-2 depends on removal of its regulator Kelch-like ECH-associated protein 1(NRF-2). In the current study, an attempt is made to demonstrate whether effects of VIT-E and CRM are due to direct interaction with the target proteins (i.e. NRF-2, NRF-2, SOD, catalase and LDH) or by possible interaction with the flanking region of their promoters by in silico analysis. Further, these results were corroborated by pretreatment of H9C2 cells (1 x 10 6 cells per mL of media) with VIT-E (50 μM) and/or CRM (20 μM) for 24 h followed by induction of oxidative stress via T4 (100 nm) administration and assaying the active oxygen metabolism. Discriminant function analyses (DFA) indicated that T4 has a definite role in increasing oxidative stress as evidenced by induction of ROS generation, increase in mitochondrial membrane potential and elevated lipid peroxidation (LPx). Pretreatment with the two antioxidants have ameliorative effects more so when given in combination. The decline in biological activities of the principal antioxidant enzymes SOD and CAT with respect to T4 treatment and its restoration in antioxidant pretreated group further validated our in silico data. Communicated by Ramaswamy H. Sarma