Vitamin D prevents glycation of proteins: an in vitro study

Abstract

Human serum albumin (HSA) is an important protein involved in the transport of hormones, fatty acids, drugs, and other macromolecules. Under hyperglycemic conditions, this molecule undergoes irreversible modification that affects its structure and function. In this study, we explored the effect of two forms of vitamin D, a nutraceutical, on glycation modification in HSA. The protein was incubated with a physiologically high concentration of glucose in the presence of vitamin D metabolites. After 21 days, samples were tested for secondary structural changes, side chain modification, and the presence of advanced glycation end products. Vitamin D metabolites could reduce glycation modification, albeit only to a small extent. Interaction studies reveal that Vitamin D interaction with HSA can prevent protein glycation.Keywords: calcitriol; glycation; protein Type 2 Diabetes is a global health issue growing at an unprecedented rate. The disease accounts for 90% of diabetes cases worldwide and is characterized by defects in glucose metabolism [1]. Persistently high blood glucose concentration encountered in diabetes often initiates Maillard reaction which causes nonenzymatic glycation of proteins and yields a plethora of reactive compounds called advanced glycation end products (AGEs) [2].Modification of protein structure and function by AGEs is consistent with the progression of diabetic complications and correlates positively with the severity of conditions like retinopathy, neuropathy, and nephropathy [3]. Once initiated, AGEs formation continues throughout the lifespan of proteins, and cannot be reversed by normalizing hyperglycemia [2,4].Human serum albumin (HSA) frequently undergoes Maillard reaction to from covalently cross-linked composites [3]. In normal adults, 6-10% of lysine chains are modified by nonenzymatic glycation, however, this number increases by 2-3 folds in individuals suffering from diabetes [5]. This may interfere with HSA function [5]. Since HSA is involved in the transportation of several moieties: nutrients, steroids, and a wide variety of drugs this can have detrimental physiological effects [6].Research suggests that vitamin D is involved in controlling AGE-associated damage in both diabetes and heart disorders [7]. Vitamin D is a fat-soluble micronutrient which is produced in the body by UV irradiation of a precursor steroid stored in the skin. The functionally active form of vitamin D, calcitriol, has a wide array of health implications [8]. Multiple studies have demonstrated its ability in limiting oxidative damage and regulating the status of a potent cellular antioxidant-reduced glutathione (GSH) [7]. Vitamin D deficiency is thought to be a risk factor for the development of diabetes; Low vitamin D status is associated with increased insulin resistance, glycated hemoglobin (HbA1c), and AGE formation [9][10][11]. Previous reports have correlated low circulating concentrations of vitamin D with increased risk of diabetic macrovascular and microvascular complications: mainly nephropathy a...

Superoxide scavenging and antiglycation activity of rhinacanthins-rich extract obtained from the leaves of Rhinacanthus nasutus

“…The nonenzymatic glycation of lysine and arginine residues in HSA, in the case of diabetes, impairs the transport of several moieties leading to detrimental physiological effects. [ 37 ] Masking of the lysine and arginine residues has therefore been proposed as an effective strategy to inhibit nonenzymatic glycation of HSA. There are two main sites in the HSA structure which offer opportunities for drug action, Sudlow's Site I and Site II.…”

Serum 25-hydroxyvitamin D3 is associated with advanced glycation end products (AGEs) measured as skin autofluorescence: The Rotterdam Study

“…Salum et al [ 18 ] recently found that oral administration of cholecalciferol led to a decrease of AGEs in the aortic wall of diabetic rats. Cholecalciferol and calcitriol prevented protein glycation in vitro [ 39 ]. Calcitriol may indirectly help with the clearance of AGEs through the kidney by protecting kidney structural integrity [ 40 ].…”

An Electrochemical Chip to Monitor In Vitro Glycation of Proteins and Screening of Antiglycation Potential of Drugs

“…The samples were collected every 7 days for up to 28 days. For the evaluation of the antiglycation compound by using the electrochemical chip, a fixed concentration of 40 g/L BSA or 2% gelatin was incubated with the hyperglycemic concentration of glucose (300 mg/dL) and inhibitory concentration of aspirin (40 mmol/L) [9,26,34,[37][38][39]. To inhibit the growth of any microorganism, 1 mmol sodium azide was supplemented in all the solutions.…”

“…In 1983, the NBT reduction assay for evaluating glycation of protein was first introduced by Johnson et al [41]. The NBT is reduced by the ketoamine form of glycated protein, which causes a change in optical density at 525-530 nm [9,42]. Previously, the NBT assay was used to evaluate the level of glycation in albumin in the diabetic patients.…”

“…The study showed that the microfluidic system can enhance the rate of in vitro glycation, but the fabricated chip was not capable of qualitative or quantitative determination of glycation. Utilizing the potential of the microfluidic chip, an impedometric sensor was fabricated for the detection of glycated Generally, before in vivo studies, in vitro glycation is utilized for the primary screening of pro-glycation and antiglycation agents [9,10]. The extent of glycation in protein samples represents the potential of the drug; a decline in glycation indicates an antiglycation property, whereas an increase indicates glycation.…”