Accumulation of Advanced Glycation Endproducts in the Rat Nephron: Link with Circulating AGEs During Aging

Abstract

SUMMARYThe accumulation of advanced glycosylation end products (AGEs) is believed to be a factor in the development of aging nephropathy. We have attempted to establish a link between the formation of AGEs and the onset of renal impairment with aging, indicated by albuminuria, using a fluorescence assay and immunohistochemical detection of AGEs in the renal extracellular matrix in rats. The fluorescence of collagenase-digested Type IV collagen from GBM increased with age, from 1.65 Ϯ 0.05 AU/mM OHPro (3 months) and 1.58 Ϯ 0.04 (10 months

Muscle Creatine Kinase Deficiency Triggers Both Actin Depolymerization and Desmin Disorganization by Advanced Glycation End Products in Dilated Cardiomyopathy

“…The following primary antibodies were used for Western blot: mouse monoclonal anti-sarcomeric ␣-actin (1:400, Sigma, recognize both cardiac and skeletal ␣-actin), mouse monoclonal anti-␣-tropomyosin, rabbit polyclonal anti-GAPDH (1:400, Santa Cruz), rabbit polyclonal anti-Histone-3 (1:400, Sigma), mouse monoclonal anti-␣B-crystallin (1:200, Abcam), and anti-phosphorylated serines 19, 45, and 59 on ␣B-crystallin (1:500, StressGen). Polyclonal anti-AGE antibody was a kind gift of Dr. Bakala and has been previously characterized (17,18). It recognizes a variety of AGE products such as carboxymethyl lysine and carboxyethyl lysine.…”

A developmental nephron deficit in rats is associated with increased susceptibility to a secondary renal injury due to advanced glycation end-products

“…AGE are a heterogeneous group of compounds, formed by the non-enzymatic reaction between reducing sugars and free amino groups of lipids, proteins or DNA. Modification of AGEs predominantly involves long-lived molecules such as extracellular matrix proteins [8,9]. AGEs accumulate with ageing [8][9][10].…”

“…Modification of AGEs predominantly involves long-lived molecules such as extracellular matrix proteins [8,9]. AGEs accumulate with ageing [8][9][10]. However, prolonged hyperglycaemia, dyslipidaemia and oxidative stress in diabetes increases the production and accumulation of AGEs [11] in the kidney and retina and at other sites of microvascular damage [12].…”

Reactive Immunization Suppresses Advanced Glycation and Mitigates Diabetic Nephropathy

“…These observations are in agreement with previous determinations of AGE accumulation in the renal extracellular matrix and their correlation with circulating AGE peptides. 8 Reduced staining in kidney of the KLHimmunized diabetic rats corroborated the association between circulating AGE levels and development of nephropathy. Immunization of some murine strains 21 as well as Lewis rat 22 with CFA can exacerbate diabetes in the subdiabetogenic STZ protocol.…”

“…A number of studies indicate that low molecular weight AGE (LMW-AGE) have increased cytotoxic potential 6 and that their levels in circulation correlate with accumulation in nephrons and impaired kidney function. 7,8 Facile diffusion through microvasculature and interstitial space, resistance to proteolytic degradation, and a high ratio of glycation to peptide mass could enhance their capacity to promote vascular pathology. Accordingly, LMW-AGE are of interest as potential biomarkers in progression of complications and as targets for therapy.…”