scholarly journals Role of zinc along with ascorbic acid and folic acid during long-term in vitro albumin glycation

2009 ◽  
Vol 103 (3) ◽  
pp. 370-377 ◽  
Author(s):  
Rashmi Santosh Tupe ◽  
Vaishali Vilas Agte
Keyword(s):  
Ascorbic Acid ◽  
Folic Acid ◽  
Cell Survival ◽  
Advanced Glycation Endproducts ◽  
Glycation Endproducts ◽  
Protein Thiols ◽  
Carbonyl Formation

The present study aimed to investigate the role of Zn alone and in the presence of ascorbic acid (AA) and folic acid (FA) in albumin glycation. Glycation was performed by incubations of bovine serum albumin with glucose at 37°C along with Zn, AA or FA separately and Zn+AA or Zn+FA for 150 d. Glycation-mediated modifications were monitored as fluorescence of advanced glycation endproducts, carbonyl formation, β aggregation (thioflavin T and Congo red dyes), albumin-bound Zn, thiol groups and glycated aggregate's toxicity in HepG2 cells. Zn inhibited glycation and β aggregation, probably due to observed higher protein-bound Zn. It also protected protein thiols and increased cell survival. AA and FA enhanced glycation, which was lowered in Zn-co-incubated samples. FA increased albumin-bound Zn and showed maximum cell survival. Although these results warrant further in vivo investigation, the present data help in the understanding of the interplay of Zn with micronutrients in albumin glycation.

Phytochemicals as Potential Inhibitors of Advanced Glycation End Products: Health Aspects and Patent Survey

2021 ◽  
Vol 12 ◽  
Author(s):  
Annayara C. F. Fernandes ◽  
Jeane B. Melo ◽  
Vanize M. Genova ◽  
Ádina L. Santana ◽  
Gabriela Macedo
Keyword(s):  
Phenolic Compounds ◽  
Inflammatory Responses ◽  
Low Cost ◽  
Advanced Glycation Endproducts ◽  
Advanced Glycation ◽  
Glycation Endproducts ◽  
Synthetic Drugs ◽  
Peanut Skins

Background: Glycation is a chemical reaction that synthesize advanced glycation endproducts (AGEs). The AGEs irreversibly damage macromolecules present in tissues and organs, leading to the impairment of biological functions. For instance, the accumulation of AGEs induces oxidative stress and consequently inflammatory responses in human body, leading to the on set/worsening of diseases, including obesity, asthma, cognitive impairment, and cancer. There is a current demand on natural and low-cost sources of antiglycant agents. As a result, food phytochemicals presented promising results to inhibit glycation and consequently, the formation of AGEs. Objective: Here, we describe the mechanism of glycation on the worsening of diseases, the methods os detection, and the current findings on the use of phytochemicals (phenolic compounds, phytosterols, carotenoids, terpenes and vitamins) as natural therapeuticals to inhibit health damages via inhibition of AGEs in vitro and in vivo. Methods: This manuscript reviewed publications available in the PubMed and Science Direct databases dated from the last 20 years on the uses of phytochemicals to inhibit the AGEs in vitro and in vivo. Also, recent patents on the use of anti-glycant drugs were reviewed using the Google Advanced Patents database. Results and Discussion: Phenolic compounds have been mostly studied to inhibit AGEs. Food phytochemicals derived from agroindustry wastes, including peanut skins, and the bagasses derived from citrus and grapes are promising antiglycant agents via scavenging of free radicals, metal ions, the suppression of metabolic pathways that induces inflammation, the activation of pathways that promote antioxidant defense, the blocking of AGE connection with the receptor for advanced glycation endproducts (RAGE). Conclusion: Phytochemicals derived from agroindustry are promising anti-glycants, which can be included to replace synthetic drugs for AGE inhibition, and consequently to act as a therapeutical strategy to prevent and treat diseases caused by AGEs, including diabetes, ovarian cancer, osteoporosis, and Alzheimer’s disease.

scholarly journals Estrogen receptors and estetrol-dependent neuroprotective actions: a pilot study

2017 ◽  
Vol 232 (1) ◽  
pp. 85-95 ◽  
Author(s):  
Ekaterine Tskitishvili ◽  
Christel Pequeux ◽  
Carine Munaut ◽  
Renaud Viellevoye ◽  
Michelle Nisolle ◽  
...  
Keyword(s):  
Estrogen Receptors ◽  
Cell Survival ◽  
Cell Cultures ◽  
Damage Model ◽  
Neuronal Cell ◽  
Concomitant Treatment ◽  
Ldh Activity

Estetrol (E4) has strong antioxidative, neurogenic and angiogenic effects in neural system resulting in the attenuation of neonatal hypoxic–ischemic encephalopathy. We aimed to define the role of estrogen receptors in E4-dependent actions in neuronal cell cultures and prove the promyelinating effect of E4. In vitro the antioxidative and cell survival/proliferating effects of E4 on H2O2-induced oxidative stress in primary hippocampal cell cultures were studied using different combinations of specific inhibitors for ERα (MPP dihydrochloride), ERβ (PHTTP), GPR30 (G15) and palmytoilation (2-BR). LDH activity and cell survival assays were performed. In vivo the promyelinating role of different concentrations of E4 (1 mg/kg/day, 5 mg/kg/day, 10 mg/kg/day, 50 mg/kg/day) was investigated using the hypoxic–ischemic brain damage model in the 7-day-old immature rats before/after the induction of hypoxic–ischemic insult. Myelin basic protein (MBP) immunostaining was performed on brain coronal sections. Our results show that LDH activity is significantly upregulated in cell cultures where the E4’s effect was completely blocked by concomitant treatment either with ERα and ERβ inhibitors (MPP and PHTPP, respectively), or ERα and ERβ inhibitors combined with 2-BR. Cell survival is significantly downregulated in cell cultures where the effect of E4 was blocked by ERβ inhibitor (PHTTP) alone. The blockage of GRP30 receptor did affect neither LDH activity nor cell survival. MBP immunostaining is significantly upregulated in E4-pretreated groups at a concentration of 5 mg/kg/day and 50 mg/kg/day E4, whereas the MBP-positive area OD ratio is significantly increased in all the E4-treated groups. E4’s antioxidative actions mostly depend on ERα and ERβ, whereas neurogenesis and possibly promyelinating activities might be realized through ERβ.

scholarly journals A karbonilstressz szerepe a diabetes szövődményeinek kialakulásában

2019 ◽  
Vol 160 (40) ◽  
pp. 1567-1573 ◽  
Author(s):  
Kinga Makk-Merczel ◽  
András Szarka
Keyword(s):  
Diabetic Complications ◽  
Clinical Studies ◽  
Advanced Glycation Endproducts ◽  
Hydroxyl Group ◽  
Carbonyl Stress ◽  
Advanced Glycation ◽  
Glycation Endproducts ◽  
Oxidative Generation

Abstract: The relationship between the potentially developing complications of the 451 million people affected by diabetes and hyperglycaemia can be based on the enhanced generation of advanced glycation endproducts and the more intensive oxidative and carbonyl stress. Advanced glycation endproducts generated partly due to carbonyl stress play an important role in the pathogenesis of diabetic complications such as elevated arterial thickness, vascular permeability, enhanced angiogenesis or the more rigid vessels induced nephropathy, neuropathy, retinopathy. Furthermore, the elevated thrombocyte aggregation, the reduced fibrinolysis induced elevated coagulation, and the atherosclerosis or the mitochondrial dysfunction are important as well. The most potent target of both the non-oxidative and oxidative generation of advanced glycation endproducts can be the scavenging of α,β-unsaturated aldehydes. Although, aminoguanidine, the prototype of scavenger molecules, showed protection in different animal models, it failed in the human clinical studies. Finally, the clinical studies were terminated almost 20 years ago. The endogen dipeptide L-carnosine was also expected to mitigate the complications due to carbonyl stress. However, its clinical significance was limited by the serum carnosinases and by the consequent low serum stability and bioavailability. The carnosinase resistance of the molecule can be achieved by the change of the carboxyl group of the molecule to hydroxyl group. At the same time, the biosafety and the carbonyl stress scavenging activity of the molecule could be preserved. Although clinical studies could not be performed in the last six months, on the basis of the in vitro and in vivo results, carnosinole seems to be a promising compound to mitigate and prevent the diabetic complications. Thus it is worth to the attention of the clinicians. Orv Hetil. 2019; 160(40): 1567–1573.

HMGB1 Derived from Macrophages Acts as an Angiogenic Factor.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3852-3852
Author(s):  
Ikuro Maruyama ◽  
Ko-ichi Kawahara ◽  
Takashi Ito ◽  
Yoko Oyama ◽  
Kazunori Takenouchi ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Advanced Glycation Endproducts ◽  
High Mobility ◽  
Cellular Migration ◽  
Angiogenic Factor ◽  
Hmgb1 Protein ◽  
Glycation Endproducts ◽  
Tumor Growth And Invasion

Abstract High Mobility Group Box-1 (HMGB1) protein, released from the most of necrotic cells and activated macrophages, has been identified as a novel cytokine through the receptor for advanced glycation endproducts (RAGE) and Toll-like receptor(TLR)-2 and -4. The HMGB1-RAGE and TLRs-2, -4 interactions contribute to cellular migration and the production of proinflammatory cytokines, and participate in pathomechanisms in tumor growth and invasion, in which an angiogenesis development is an important aspect. We here show that HMGB1 stimulates the expression of Vascular Endothelial Growth Factor (VEGF), the most potent angiogenic factor in tumors, through the HMGB1-RAGE, but neither TLR-2 nor TLR-4 in macrophage-lineage cells in vitro. The mechanism of VEGF production is mediated through the Akt pathway, which is linked to tumor growth and invasion. Furthermore, HMGB1 induced angiogenesis was also observed in an in vivo rabbit corneal assay (Fig). These results suggest that HMGB1, released from the tumor-associated macrophages, may act as a key cytokine in the development of angiogenesis by producing VEGF in tumor growth and invasion. Thus the tumor-associated HMGB1/RAGE system may contribute to our understanding of the mechanism of cancer cell escape from macrophage-associated acceleration of inflammation.

scholarly journals Collagen metabolism in folic acid deficiency

1974 ◽  
Vol 32 (2) ◽  
pp. 457-469 ◽  
Author(s):  
J. G. A. J. Hautvast ◽  
M. J. Barnes
Keyword(s):  
Ascorbic Acid ◽  
Protein Synthesis ◽  
Folic Acid ◽  
Growth Characteristic ◽  
Male Rats ◽  
Folic Acid Deficiency ◽  
Collagen Formation ◽  
Acid Deficiency

1. The effect of folic acid deficiency on collagen formation, with respect to the level of collagen-protein synthesis and the extent of collagen-proline hydroxylation, has been studied. A folic acid-free diet containing 10 g sulphasuxidine/kg was used to induce folate deficiency in young male rats. Animals were judged folic acid-deficient on the grounds of retardation of growth, characteristic haematological changes and the urinary excretion of formimino-L-glutamic acid.2. From isotope incorporation studies it was found that folic acid deficiency caused a marked impairment in collagen synthesis. It was shown, however, from the use of pair-fed control animals, that this was due in part to a reduced food intake accompanying the vitamin deficiency. The further reduction in synthesis in addition to that attributable to inanition was considered to arise from an involvement of folic acid in general protein synthesis, since it was found that the synthesis of elastin and non-collagenous skin proteins was similarly impaired.3. Reduced synthesis of collagen was not considered attributable to lack of hydroxylation of peptidyl proline that may occur in ascorbic acid deficiency. Hydroxylation of collagen- and elastin-proline was only very slightly impaired in folic acid deficiency. It was concluded that, at least when ascorbic acid is present, folic acid is not directly essential for the hydroxylation, in vivo, of peptidyl proline. The results support the view that ascorbic acid participates direct, in vivo, in this hydroxylation rather than indirect by simply maintaining an adequate level of reduced folates. They do not, however, exclude the possibility, arising from the known ability of tetrahydrofolate to participate in the hydroxylation of collagen proline in vitro, that when both ascorbate and folate are present, the latter may, in some measure, share in the role of reducing agent in the hydroxylation of peptidyl proline in vivo.

scholarly journals The Pim kinases control rapamycin-resistant T cell survival and activation

2005 ◽  
Vol 201 (2) ◽  
pp. 259-266 ◽  
Author(s):  
Casey J. Fox ◽  
Peter S. Hammerman ◽  
Craig B. Thompson
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Cell Survival ◽  
Growth And Survival ◽  
Pim Kinases ◽  
T Cell Survival

Although Pim-1 or Pim-2 can contribute to lymphoid transformation when overexpressed, the physiologic role of these kinases in the immune response is uncertain. We now report that T cells from Pim-1−/−Pim-2−/− animals display an unexpected sensitivity to the immunosuppressant rapamycin. Cytokine-induced Pim-1 and Pim-2 promote the rapamycin-resistant survival of lymphocytes. The endogenous function of the Pim kinases was not restricted to the regulation of cell survival. Like the rapamycin target TOR, the Pim kinases also contribute to the regulation of lymphocyte growth and proliferation. Although rapamycin has a minimal effect on wild-type T cell expansion in vitro and in vivo, it completely suppresses the response of Pim-1−/−Pim-2−/− cells. Thus, endogenous levels of the Pim kinases are required for T cells to mount an immune response in the presence of rapamycin. The existence of a rapamycin-insensitive pathway that regulates T cell growth and survival has important implications for understanding how rapamycin functions as an immunomodulatory drug and for the development of complementary immunotherapeutics.

Role of osteoprotegerin (OPG) in cancer

2006 ◽  
Vol 110 (3) ◽  
pp. 279-291 ◽  
Author(s):  
Ingunn Holen ◽  
Claire M. Shipman
Keyword(s):  
Cell Survival ◽  
Tumour Cell ◽  
Bone Disease ◽  
In Vitro Models ◽  
Tumour Cells ◽  
Tumour Necrosis Factor Receptor ◽  
Area Of Interest

OPG (osteoprotegerin), a secreted member of the TNF (tumour necrosis factor) receptor superfamily, has a variety of biological functions which include the regulation of bone turnover. OPG is a potent inhibitor of osteoclastic bone resorption and has been investigated as a potential therapeutic for the treatment of both osteoporosis and tumour-induced bone disease. Indeed, in murine models of cancer-induced bone disease, inhibition of osteoclastic activity by OPG was also associated with a reduction in tumour burden. The discovery that OPG can bind to and inhibit the activity of TRAIL (TNF-related apoptosis-inducing ligand) triggered extensive research into the potential role of OPG in the regulation of tumour cell survival. A number of reports from studies using in vitro models have shown that OPG protects tumour cells from the effects of TRAIL, thereby possibly providing tumour cells that produce OPG with a survival advantage. However, the ability of OPG to act as a tumour cell survival factor remains to be verified using appropriate in vivo systems. A third area of interest has been the use of OPG as a prognostic marker in various cancer types, including myeloma, breast and prostate cancer. This review provides an overview of the role of OPG in cancer, both in cancer-induced bone disease and in tumour growth and survival.

scholarly journals Dietary Sugars and Endogenous Formation of Advanced Glycation Endproducts: Emerging Mechanisms of Disease

2017 ◽  
Author(s):  
Manuela Aragno ◽  
Raffaella Mastrocola
Keyword(s):  
Metabolic Diseases ◽  
Advanced Glycation Endproducts ◽  
Lipid Synthesis ◽  
Advanced Glycation ◽  
Antioxidant Defences ◽  
Glycation Endproducts ◽  
Cell Functions ◽  
Dietary Sugars

The rapid increase in metabolic diseases occurred in the last three decades in both industrialized and developing countries has been related to the rise in sugar-added foods and sweetened beverages consumption. An emerging topic in the pathogenesis of metabolic diseases related to modern nutrition is the role of Advanced Glycation Endproducts (AGEs). AGEs can be ingested with high temperature processed foods, but also endogenously formed as consequence of a high dietary sugars intake. Animal models of high sugars consumption, in particular fructose, have reported AGEs accumulation in different tissues in association with peripheral insulin resistance and lipid metabolism alterations. The in vitro observation that fructose is one of the most rapid and effective glycating agent when compared to other sugars has prompted the investigation of the in vivo fructose-induced glycation. In particular, the widespread employment of fructose as sweetener has been ascribed by many experimental and observational studies for the enhancement of lipogenesis and intracellular lipid deposition. Indeed, diet-derived AGEs have been demonstrated to interfere with many cell functions such as lipid synthesis, inflammation, antioxidant defences, and mitochondrial metabolism. Moreover, emerging evidences also in humans suggest that this impact of dietary AGEs on different signalling pathways can contribute to the onset of organ damage in liver, skeletal and cardiac muscle, and brain, affecting not only metabolic control, but global health. Indeed, the here reviewed most recent reports on the effects of high sugars consumption and diet-derived AGEs on human health suggest the need to limit the dietary sources of AGEs, including added sugars, to prevent the development of metabolic diseases and related comorbidities.

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