Humans ; Lung Neoplasms ; metabolism ; Receptor for Advanced Glycation End Products ; metabolism

This study was aimed to investigate the effect of advanced glycosylation end products (AGE) on the proliferation of K562 and K562/A02 cells, the effect of tetrandrine (Tet) on proliferation of K562 and K562/A02 cells induced by AGE, and their mechanisms. The effects of AGE on proliferation of K562 and K562/A02 cells and Tet on the proliferation of AGE-induced K562 and K562/A02 cells were assayed by CCK8 kit, the apoptosis rate and the expression of receptor of advanced glycosylation end products (RAGE) in K562 and K562/A02 cells were determined by flow cytometry, the expression of RAGE mRNA was detected by semi-quantitative RT-PCR. The results showed that AGE could promote the proliferation of K562 and K562/A02 cells in a concentration-dependent manner, the cell proliferation was enhanced with time increasing in 0 - 48 h, and was higher than control group after 72 h. AGE up-regulated the RAGE mRNA and protein expressions of K562 and K562/A02 cells in a concentration-dependent manner. Treatment of Tet combined with AGE for 48 h could inhibit the proliferation of K562 and K562/A02 cells promoted by AGE in a concentration-dependent manner, which probably by inducing cell apoptosis, however, there was no obvious effect in the up-regulating expression of RAGE mRNA and protein induced by AGE. It is concluded that AGE can promote the proliferation of K562 and K562/A02 cells, which is probably induced by up-regulating the expression of RAGE mRNA and protein. Tet can inhibit the proliferation of K562 and K562/A02 cells induced by AGE, and the mechanism may be not closely associated with changes of the up-regulating expression of RAGE mRNA and protein induced by AGE.
Apoptosis ; drug effects ; Benzylisoquinolines ; pharmacology ; Cell Proliferation ; drug effects ; Gene Expression Regulation, Leukemic ; Glycation End Products, Advanced ; pharmacology ; Humans ; K562 Cells ; Receptor for Advanced Glycation End Products ; metabolism

Atherosclerosis ; pathology ; C-Reactive Protein ; metabolism ; Dendritic Cells ; metabolism ; Glycation End Products, Advanced ; metabolism ; Humans ; Inflammation

The number of patients with diabetic foot ulcer (DFU) has increased progressively year by year. Refractory DFU has brought great burden to the country and individuals. How to accelerate the healing of DFU has become the main emphasis of research. However currently, the mechanism of its refractory healing is not fully elucidated, and the correlation between the various mechanisms are not high. Therefore, its clinical standardization, and precise clinical diagnosis and treatment still face several challenges. Based on the progress of clinical research and basic research at home and abroad, this paper reviewed the specific mechanisms that lead to refractory DFU, with the focus on chronic inflammation, bacteria biofilm formation, high oxidative stress, growth factor inhibition, impaired microcirculation, and accumulation of advanced glycation end products.
Humans ; Diabetic Foot/metabolism* ; Wound Healing ; Glycation End Products, Advanced/metabolism* ; Diabetes Mellitus

This review reflects upon our own as well as other investigators' studies on the role of receptor for advanced glycation end-products (RAGE), bringing up the latest information on RAGE in physiology and pathology of the nervous system. Over the last ten years, major progress has been made in uncovering many of RAGE-ligand interactions and signaling pathways in nervous tissue; however, the translation of these discoveries into clinical practice has not come to fruition yet. This is likely, in part to be the result of our incomplete understanding of this crucial signaling pathway. Clinical trials examining the therapeutic efficacy of blocking RAGE-external ligand interactions by genetically engineered soluble RAGE or an endogenous RAGE antagonist, has not stood up to its promise; however, other trials with different blocking agents are being considered with hope for therapeutic success in diseases of the nervous system.
Humans ; Ligands ; Nervous System Diseases ; Receptor for Advanced Glycation End Products/metabolism* ; Signal Transduction/physiology*

OBJECTIVETo investigate the accumulation of advanced glycation end products (AGEs) and expression of receptor for AGEs (RAGE) in streptozocin (STZ)-induced diabetic nephropathy in rats, and the role of antioxidants on the AGEs-RAGE signaling.

METHODSDiabetic rats were induced by once intraperitoneal injection of STZ at the dose of 60 mg/kg, and randomly divided into the DN group (n=12, treated with normal saline by intraperitoneal injection, once daily), the extract of Ginkgo biloba (EGb) group (n=14, treated with EGb 300 mg/kg by oral administration, once every other day), and the alpha-lipoic acid (ALA) group (n=12, treated with ALA at the dose of 35 mg/kg by intraperitoneal injection, once every other day). Rats of the normal control group (n=10) were given vehicle citrate buffer at the dose of 60 mg/kg. Rats were sacrificed at the 12th week and the 20th week of this study. The four groups were compared in terms of body weight, blood glucose, renal function, 24-h urine protein. Renal pathological changes were observed by PAS staining. Oxidative stress indices were detected using spectrophotometry. The concentrations of AGEs were measured using fluoro spectrophotometry, and the expressions of RAGE were detected by Real-time PCR and Western blot.

RESULTSCompared with the normal control group, the 24-h urine protein quantitation was higher and the glomerular filtration rate increased in rats at the 12th week and the 20th week. The pathological tissue staining showed dilated glomerular mesangium, proliferated glomerular matrix, vacuolar degeneration of the renal tubular epithelium. Malonaldehyde (MDA) levels and 8-hydroxide radical guanine deoxyriboside (8-OHdG) levels increased, and catalase (CAT) and reduced glutathione hormone (GSH) levels decreased. The AGEs contents in serum and renal tissue homogenate increased. The expressions of RAGE mRNA and protein increased in the DN group at the 12th and the 20th week. The 24-h urine protein quantitation was reduced in the EGb group and the ALA group, with alleviated pathological changes, lowered MDA and 8-OHdG levels, increased CAT and GSH levels, decreased AGEs contents, and down-regulated RAGE expressions.

CONCLUSIONSAGEs contents increased and RAGE expression up-regulated in the circulation and local renal tissues in DN rats. EGb and ALA could inhibit AGEs production and down-regulate RAGE expressions by reducing oxidative stress, thus further improving the renal tissue structure and renal functions of DN rats. It had better application prospect in treatment and prevention of DN.

Animals ; Antioxidants ; pharmacology ; Diabetes Mellitus, Experimental ; metabolism ; Diabetic Nephropathies ; metabolism ; Ginkgo biloba ; Glycation End Products, Advanced ; metabolism ; Kidney ; metabolism ; Male ; Rats ; Rats, Wistar ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic ; metabolism ; Thioctic Acid ; pharmacology

The diabetic ulceration is not uncommon, and becomes refractory, as the skin in a diabetic patient is relatively thin as well as hypoesthetic and less sensitive to temperature. As there are already preexisting histological and cellular derangement in the skin, healing of the skin injury is difficult, thus resulting in an intractable ulceration. When diabetes is not controlled, the skin contents of sugar and advanced glycation end product accumulate, invoking cellular deformation and accumulation of matrix metalloproteinases (MMP), resulting in an imbalance between MMP and its inhibitors, malfunction of growth factors, and inflammatory reaction. These processes lead to obvious skin thinning, denaturation of connective tissues, thickening of vascular basal membrane, and neuropathy, etc. These pathological alterations could be recognized as "covert disorder" of skin in diabetic patients and may be underlying disorders in producing indolent diabetic ulcers.
Animals ; Diabetes Mellitus ; metabolism ; pathology ; Glycation End Products, Advanced ; metabolism ; Rats ; Skin ; metabolism ; pathology ; Skin Ulcer ; pathology ; Wound Healing

OBJECTIVETo investigate the effects of advanced glycosylation end products (AGEs) modified bovine serum albumin (AGE-BSA) on the expression of reactive oxygen species (ROS) and monocyte chemoattractant protein-1 (MCP-1) in human renal mesangial cells (HRMCs).

METHODSHRMCs were cultured in vitro with medium containing different doses of AGE-BSA or BSA (50,100, 200, 400 mg/L) for 48 hours, or with AGE-BSA (200 mg/L) for different times (12, 24, 48, 72 h). Immunocytochemistry assay was used to estimate the protein level of RAGE. The ROS in cells were measured by flow cytometry and the mRNA expression of MCP-1 were analyzed by semi-quantiative reverse transcription-polymerase chain reaction (RT-PCR) after treatment with AGE-BSA or BSA.

RESULTSThe protein level of RAGE was upregulated in the HRMCs with AGE-BSA. The expression of ROS and MCP-1 significantly enhanced by incubation of AGE-BSA in a time- and dose-dependent manner. The effects of AGE-BSA-induced up-regulation of ROS and MCP-1 level was significantly blocked by neutralizing antibodies to RAGE, while the expression of ROS and MCP-1 stood nearly unchanged after cultured with huamn IgG.

CONCLUSIONThe expression of ROS and MCP-1 in HRMCs is induced by AGE-BSA through RAGE, which may have potential effects in the pathgenic mechanism of diabetic nephropathy.

Cells, Cultured ; Chemokine CCL2 ; metabolism ; Glycation End Products, Advanced ; pharmacology ; Humans ; Mesangial Cells ; drug effects ; metabolism ; Oxidative Stress ; drug effects ; Reactive Oxygen Species ; metabolism ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic ; metabolism ; Serum Albumin, Bovine ; pharmacology

OBJECTIVETo study the effects of advanced glycosylation end products (AGEs) on the production of fibronectin (FN) in human peritoneal mesothelial cells (HPMC) in vitro and the role of protein kinase C (PKC) in this course.

METHODSThe AGE-human serum albumin (HSA) (0, 100, 500, 1 000 microg/ml) was used in culture medium to stimulate the HPMC. The mRNA level of FN was measured with real-time PCR, moreover, the protein level of FN in HPMC was detected by ELISA. With the method of ELISA, the PKC activities were observed. Inhibitors or activators of PKC were used to observe the roles of PKC pathways on the AGE-HSA stimulated productions of FN in HPMC.

RESULTSAGE-HSA activated PKC in HPMC in a dose, time-dependent manner (P < 0.05). AGE-HSA up-regulated the expression of FN mRAN and protein in dose- and time-dependently (P < 0.01); PKC activator phorbol 12-myristate 13-acetate (PMA) induced FN expression, respectively depletion of PKC and calphostin C, a PKC inhibitor, effectively prevented both PMA and AGE-HSA-induced expression of the FN (P < 0.05).

CONCLUSIONAGEs can increase the activities of PKC. AGEs can directly increase FN expression in HPMC which may contribute to peritoneal fibrosis and this is regulated by PKC.

Cells, Cultured ; Epithelium ; secretion ; Fibronectins ; metabolism ; Glycation End Products, Advanced ; pharmacology ; Humans ; Peritoneum ; cytology ; Protein Kinase C ; metabolism

OBJECTIVETo study the expression of the receptor for advanced glycation end products (RAGE) and the inhibitory effect of advanced glycation end products (AGEs) on testosterone production in rat Leydig cells.

METHODSRat Leydig cells were primarily cultured and the expression of RAGE in the Leydig cells was detected by RT-PCR and immunofluorescence staining. The Leydig cells were treated with AGEs at the concentrations of 25, 50, 100 and 200 microg/ml, respectively, and the testosterone content was determined by ELISA.

RESULTSRT-PCR and immunofluorescence staining exhibited the expression of RAGE in the rat Leydig cells. AGEs remarkably suppressed hCG-induced testosterone production in the Leydig cells in a concentration-dependent manner in the 50, 100 and 200 microg/ml groups as compared with the control (P < 0.01).

CONCLUSIONRAGE exists in rat Leydig cells and AGEs can significantly inhibit the secretion of testosterone in primarily cultured rat Leydig cells.

Animals ; Cells, Cultured ; Enzyme-Linked Immunosorbent Assay ; Glycation End Products, Advanced ; pharmacology ; Leydig Cells ; metabolism ; radiation effects ; Male ; Rats ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic ; biosynthesis ; Reverse Transcriptase Polymerase Chain Reaction ; Testosterone ; biosynthesis