Effect of chemical chaperones on glucose-induced lysozyme modifications

Nonenzymatic glycation of biomacromolecules occurs due to the diabetes mellitus and ageing. A number of small molecules, known as chemical chaperones, stabilize protein conformation against thermal and chemically induced denaturation. These compounds are including: polyamines (e.g. spermine and spermidine), amino acids (e.g. lysine) and polyols (e.g. glycerol). In this study the effect of spermidine (Spd), spermine (Spm), and glycerol on glycation, structure and function of lysozyme (LZ), as an extra-cellular protein, by different techniques is investigated. LZ is incubated with or without glucose (50 or 100 mM) in the absence or presence of Spd/Spm/glycerol at 37 °C up to 16 weeks. All the observed changes of glycated-LZ in comparison with the native protein, including: increased fluorescence emission, alteration in the secondary and tertiary structure, and reduced electrophoretic mobility- indicate its structural changes that are accompanied with its reduced activity. Glucose in the presence or absence of Spd induces the protein dimerization, but glucose plus Spm induces its trimmerization. In contrast, glycerol inhibits the LZ glycation and prevents the large changes on its structure and function. Glucose binds lysine residues, decreases the protein positive charges and induces some alterations in its structure and activity. Polyamines also directly bind to LZ, increase its positive charges and hence induce more glycation; more conformational changes, oligomerization and its inactivation in the presence of glucose, but glycerol affect the protein environment and preserve protein from these harmful effects. © 2011 Springer Science+Business Media, LLC

Inhibitory effect of crocin(s) on lens crystallin glycation and aggregation, results in the decrease of the risk of diabetic cataract

The current study investigates the inhibitory effect of crocin(s), also known as saffron apocarotenoids, on protein glycation and aggregation in diabetic rats, and α-crystallin glycation. Thus, crocin(s) were administered by intraperitoneal injection to normal and streptozotocin-induced diabetic rats. The cataract progression was recorded regularly every two weeks and was classified into four stages. After eight weeks, the animals were sacrificed and the parameters involved in the cataract formation were measured in the animal lenses. Some parameters were also determined in the serum and blood of the rats. In addition, the effect of crocin(s) on the structure and chaperone activity of α-crystallin in the presence of glucose was studied by different methods. Crocin(s) lowered serum glucose levels of diabetic rats and effectively maintained plasma total antioxidants, glutathione levels and catalase activity in the lens of the animals. In the in vitro study, crocin(s) inhibited α-crystallin glycation and aggregation. Advanced glycation end products fluorescence, hydrophobicity and protein cross-links were also decreased in the presence of crocin(s). In addition, the decreased chaperone activity of α-crystallin in the presence of glucose changed and became close to the native value by the addition of crocin(s) in the medium. Crocin(s) thus showed a powerful inhibitory effect on α-crystallin glycation and preserved the structure-function of this protein. Crocin(s) also showed the beneficial effects on prevention of diabetic cataract. © 2016 by the authors

Assessment of oral glycine and lysine therapy on receptor for advanced glycation end products and transforming growth factor beta expression in the kidney of streptozotocin-induced diabetic rats in comparison with normal rats

Background & Aims: Today, diabetic nephropathy is considered to be one of the most common causes of end stage renal disease. Uncontrolled hyperglycemia, and consequently, production of advanced glycation end products activate pathways which play key roles in diabetic nephropathy. Among these pathways, high expression of receptor for advanced glycation end products (RAGE) and transforming growth factor beta (TGFβ) are notable. In this study, in order to find compounds which can prevent the incidence or progression of diabetic nephropathy, we examined the effects of glycine and lysine amino acids on expression of RAGE and TGFβ in kidney tissue of diabetic rats. Methods: After rendering rats with diabetes with streptozotocin (STZ), they were divided into different groups and were treated with oral 1 glycine and 0.1 lysine in drinking water for 12 weeks. Blood glucose and serum AGEs were measured during this time. Changes in RAGE and TGFβ expression were assessed by semi quantitative reverse transcription polymerase chain reaction (RT-PCR) method. Results: Results show that both glycine and lysine administration for 12 weeks not only caused a significant reduction in blood glucose and AGEs in diabetic rats, but also led to a significant reduction in RAGE and TGFβ expression in comparison to non-treated diabetic rats. Conclusion: These results show that oral glycine and lysine, as chemical chaperones, have the ability to prevent diabetic nephropathy by decreasing RAGE and TGFβ expression. This may be due to the effect of these chemical chaperones in the reduction of hyperglycemia and serum AGEs in diabetic rats. Since the positive effects of these amino acids in diabetic nephropathy have been observed in previous studies, the determination of their dose in future studies seems necessary. © 2014, Kerman University of Medical Sciences. All rights reserved

Prerequisite of a Holistic Blend of Traditional and Modern Approaches of Cancer Management

Background: With the advent of changes in lifestyle of people all around the world, cancer cases have been showing an exponential rise. Researchers from varied fields have been trying to solve this tricky issue. Methods: We undertook a systematic search of bibliographic databases of peer-reviewed research literature to evaluate the holistic blend of modern and traditional approaches, especially the Ayurvedic perspective of treatment of cancer along with the effect of our diet and lifestyle on the management (both prevention and cure) of cancer. Results: On the basis of extensive literature survey, it was found that Ayurveda as one of the ancient medicinal systems had been very well documented for utilizing its best practices for the treatment of various diseases including cancer, by utilization of several herbal plants and dietary interventions as therapeutics. Active components present in various herbs, which interfere with certain molecular targets to inhibit carcinogenesis are also summarized. Further, beneficial effects of yoga and exercise on psychological distress, cancer-related fatigue and global side-effects as well as their mechanism of action are also discussed. In addition, we recapitulate an upcoming field of Ayurgenomics to understand the possible correlation of Prakriti with genetics as well as epigenetics. Conclusion: Both genetic as well as environmental factors have shown their linkage with cancer. Substantial advancements in the field of targeted therapies have opened new horizons for the cancer patients. To fight with this grave situation, a combination of ancient and modern medicinal systems seems to be the need of the hour