Publications by authors named "Bavani Arumugam"

4 Publications

  • Page 1 of 1

Role of surface-exposed charged basic amino acids (Lys, Arg) and guanidination in insulin on the interaction and stability of insulin-insulin receptor complex.

Comput Biol Chem 2021 Jun 24;92:107501. Epub 2021 Apr 24.

Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia. Electronic address:

Naturally occurring proteins are emerging as novel therapeutics in the protein-based biopharmaceutical industry for the treatment of diabetes and obesity. However, proteins are not suitable for oral delivery due to short half-life, reduced physical and chemical stability and low permeability across the membrane. Chemical modification has been identified as a formulation strategy to enhance the stability and bioavailability of protein drugs. The present study aims to study the effect of charge-specific modification of basic amino acids (Lys, Arg) and guanidination on the interaction of insulin with its receptor using molecular modelling. Our investigation revealed that the guanidination of insulin (Lys-NHC = NHNH) enhanced and exerted stronger binding of the protein to its receptor through electrostatic interaction than native insulin (Lys-NH). Point mutations of Lys and Arg (R22, K29; R22K, K29; R22, K29R; R22K, K29R) were attempted and the effects on the interaction and stability between insulin/modified insulins and insulin receptor were also analyzed in this study. The findings from the study are expected to provide a better understanding of the possible mechanism of action of the modified protein at a molecular level before advancing to real experiments.
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http://dx.doi.org/10.1016/j.compbiolchem.2021.107501DOI Listing
June 2021

Protective effect of myricetin derivatives from against hydrogen peroxide-induced stress in ARPE-19 cells.

Mol Vis 2019 7;25:47-59. Epub 2019 Feb 7.

Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Purpose: Oxidative stress is implicated in the etiology of diabetes and its debilitating complications, such as diabetic retinopathy (DR). Various flavonoids have been reported to be useful in reducing DR progression. Myricetin derivatives (F2) isolated from leaf extract of have the potential to serve as functional food as reported previously. The present study was performed with the aim of determining the antioxidant potential and protective effect of myricetin derivatives (F2) isolated from leaf extract of against glucose oxidase (GO)-induced hydrogen peroxide (HO) production that causes oxidative stress in ARPE-19 (RPE) cells.

Methods: Antioxidant properties were assessed through various radical (DPPH, ABTS, and nitric oxide) scavenging assays and determination of total phenolic content and ferric reducing antioxidant power level. ARPE-19 cells were preincubated with samples before the addition of GO (to generate HO). Cell viability, change in intracellular reactive oxygen species (ROS), HO levels in cell culture supernatant, and gene expression were assessed.

Results: F2 showed higher antioxidant levels than the extract when assessed for radical scavenging activities and ferric reducing antioxidant power. F2 protected the ARPE-19 cells against GO-HO-induced oxidative stress by reducing the production of HO and intracellular reactive oxygen species. This was achieved by the activation of nuclear factor erythroid 2-related factor 2 (Nrf2/) and superoxide dismutase (), as well as downregulation of nitric oxide producer () at the transcriptional level.

Conclusions: The results showed that myricetin derivatives from have the capacity to exert considerable exogenous antioxidant activities and stimulate endogenous antioxidant activities. Therefore, these derivatives have excellent potential to be developed as therapeutic agents for managing DR.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379087PMC
June 2019

Leucaena leucocephala fruit aqueous extract stimulates adipogenesis, lipolysis, and glucose uptake in primary rat adipocytes.

ScientificWorldJournal 2014 10;2014:737263. Epub 2014 Aug 10.

Faculty of Medicine, Segi University, Selangor 47810, Malaysia.

Leucaena leucocephala had been traditionally used to treat diabetes. The present study was designed to evaluate in vitro "insulin-like" activities of Leucaena leucocephala (Lam.) deWit. aqueous fruit extract on lipid and glucose metabolisms. The ability of the extract to stimulate adipogenesis, inhibit lipolysis, and activate radio-labeled glucose uptake was assessed using primary rat adipocytes. Quantitative Real-Time RT-PCR was performed to investigate effects of the extract on expression levels of genes (protein kinases B, AKT; glucose transporter 4, GLUT4; hormone sensitive lipase, HSL; phosphatidylinositol-3-kinases, PI3KA; sterol regulatory element binding factor 1, Srebp1) involved in insulin-induced signaling pathways. L. leucocephala aqueous fruit extract stimulated moderate adipogenesis and glucose uptake into adipocytes when compared to insulin. Generally, the extract exerted a considerable level of lipolytic effect at lower concentration but decreased gradually at higher concentration. The findings concurred with RT-PCR analysis. The expressions of GLUT4 and HSL genes were upregulated by twofold and onefold, respectively, whereas AKT, PI3KA, and Srebp1 genes were downregulated. The L. leucocephala aqueous fruit extract may be potentially used as an adjuvant in the treatment of Type 2 diabetes mellitus and weight management due to its enhanced glucose uptake and balanced adipogenesis and lipolysis properties.
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http://dx.doi.org/10.1155/2014/737263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4142670PMC
May 2015

Succinylation-induced conformational destabilization of lysozyme as studied by guanidine hydrochloride denaturation.

J Biochem 2009 Dec 28;146(6):895-904. Epub 2009 Aug 28.

Biomolecular Research Group, Biochemistry Programme, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.

Using 100-fold molar excess of succinic anhydride, about 99% of lysine residues of hen egg white lysozyme (HEWL) were modified. Succinylated (S(99)) HEWL showed both charge and size homogeneity as judged by PAGE and gel filtration, respectively. Hydrodynamic parameters such as Stokes radius and frictional ratio (f/f(o)) showed more expanded conformation of S(99) HEWL compared to native HEWL as evident from the increase in Stokes radius (from 1.36 to 1.86 nm) and f/f(o) (from 0.86 to 1.15) values. Guanidine hydrochloride (GdnHCl) denaturation studies using fluorescence spectroscopy connoted a marked decrease in conformational stability of HEWL upon succinylation. Complete denaturation of S(99) HEWL was achieved at lower GdnHCl concentration ( approximately 3.8 M) compared to native HEWL ( approximately 5 M). Furthermore, free energy of stabilization (DeltaG(D)(H(2)O)) value also showed a notable decrease from 8,559 and 7,956 cal/mol (for native HEWL) to 4,404 and 4,669 cal/mol (for succinylated HEWL) using excitation at 280 and 295 nm, respectively. Both expanded conformation and decreased DeltaG(D)(H(2)O) can be attributed to the increase in the net negative charge on the protein upon succinylation. All these results manifested the importance of positively charged lysine residues in maintaining the conformational stability of HEWL through electrostatic interactions.
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http://dx.doi.org/10.1093/jb/mvp136DOI Listing
December 2009