Acrolein (CH 2 =CH—CHO) is known as a ubiquitous pollutant in the environment. Here we show that this notorious aldehyde not just pollutant, but also lipid peroxidation product could be ubiquitously generated biological systems. Upon incubation with BSA, acrolein was rapidly incorporated into protein and protein-linked carbonyl derivative, putative marker of oxidatively modified proteins under oxidative stress. To verify presence protein-bound vivo , mAb (mAb5F6) against acrolein-modified...

The glycosylphosphatidylinositol (GPI) anchor is a membrane attachment structure of many proteins and occurs in wide variety eukaryotes from yeasts to mammals. the core GPI conserved protozoa mammals so its biosynthetic pathway. A complementary DNA encoding human protein termed PIG-A (phosphatidylinositol glycan-class A) was cloned. necessary for synthesis N -acetylglucosaminyl-phosphatidylinositol, very early intermediate GPI-anchor biosynthesis.

Advanced glycation end products (AGEs) include a variety of protein adducts whose accumulation alters the structure and function tissue proteins stimulates cellular responses. They have been implicated in damage associated with diabetic complications. To assess possible link between AGE development nephropathy (DN), we examined immunohistochemical localization various structures postulated to date, i.e., pentosidine, Nepsilon-(carboxymethyl)lysine (CML), pyrraline, control kidneys. CML...

beta 2-Microglobulin (beta 2M) is a major constituent of amyloid fibrils in hemodialysis-associated amyloidosis, complication long-term hemodialysis patients. Amyloid fibril proteins were isolated from connective tissues forming carpal tunnels patients with tunnel syndrome. Two-dimensional polyacrylamide gel electrophoresis and Western blotting demonstrated that most the 2M exhibited more acidic pI value than normal 2M. This was also found small fraction sera urine these patients, whereas...

beta 2-Microglobulin (beta 2M) is a major constituent of amyloid fibrils in hemodialysis-associated amyloidosis (HAA), complication long-term hemodialysis. However, the pathological role 2M HAA remains to be determined. Recently, we demonstrated that deposits modified with advanced glycation end products (AGEs) Maillard reaction. Since AGEs have been implicated tissue damage associated diabetic complications and aging, investigated possible involvement AGE-modified (AGE-beta pathogenesis...

An important component of amyloid fibrils in dialysis-related amyloidosis is a form beta2microglobulin modified with advanced glycation end products (AGEs) the Maillard reaction, known as AGE-beta2M. We demonstrate here that interaction AGE-beta2M mononuclear phagocytes (MPs), cells pathogenesis inflammatory arthropathy amyloidosis, mediated by receptor for AGEs, or RAGE. 125I-AGE-beta2M bound to immobilized RAGE MPs specific, dose-dependent manner (Kd approximately 53.5 and 81.6 nM,...

ABSTRACT. The implication of advanced glycation end products (AGE) in the pathogenesis atherosclerosis and diabetic uremic complications has stimulated a search for AGE inhibitors. This study evaluates inhibitory potential several well-tolerated hypotensive drugs. Olmesartan, an angiotensin II type 1 receptor (AIIR) antagonist, as well temocaprilat, angiotensin-converting enzyme (ACE) inhibitor, unlike nifedipine, calcium blocker, inhibit vitro formation two AGE, pentosidine...

Abstract. Advanced glycation end products (AGE) include a variety of protein adducts whose accumulation has been implicated in tissue damage associated with diabetic nephropathy (DN). It was recently demonstrated that among AGE, glycoxidation products, formation is closely linked to oxidation, such as carboxymethyllysine (CML) and pentosidine, accumulate expanded mesangial matrix nodular lesions DN, colocalization malondialdehyde-lysine (MDA-lysine), lipoxidation product, whereas pyrraline,...

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder in which there a deficiency the synthesis by hematopoietic cells of glycosyl-phosphatidylinositol molecules that anchor proteins to cell membrane. Recently, we demonstrated gene termed PIG-A (for phosphatidylinositol glycan class A), component biosynthesis, was responsible for PNH two patients. The present study undertaken elucidate whether all cases and characterize further somatically abnormalities this gene.

Pentosidine is an advanced glycation end product and its formation shown to be closely related oxidative processes. Recent studies have that pentosidine levels are increased not only in plasma matrix proteins from diabetic patients, but also markedly nondiabetic hemodialysis patients. Currently, the mechanism of accumulation kinetics patients remain unknown. Gel filtration uremic revealed exists albumin fraction (approximately 90%) and, interestingly, free form 5%) as well. Plasma was...

ABSTRACT. The remnant kidney model is a mainstay in the study of progressive renal disease. earliest changes this result from glomerular hemodynamic alterations. Given that disease subsequent interstitial damage initiated by undetermined pathogenic factors, authors investigated role hypoxia as factor tubulointerstitial after ablation rats. Cortical tissue early phase (4 and 7 d) rats, sham-operated animals treated with angiotensin II receptor blocker (ARB) olmesartan (10 mg/kg per was...

4-Hydroxynonenal (HNE), a diffusible product of lipid peroxidation, has been suggested to be key mediator oxidative stress-induced cell death. In this study, we partially characterized the mechanism HNE-mediated cytotoxicity. Incubation human T lymphoma Jurkat cells with 20-50 microM HNE led death accompanied by DNA fragmentation. Western blot analysis showed that HNE-treatment induced time- and dose-dependent activation caspase-8, caspase-9 caspase-3. HNE-induced caspase-3 processing was...

The reactive advanced glycation end product (AGE) precursor methylglyoxal (MGO) and MGO-derived AGEs are associated with diabetic vascular complications also an increase in oxidative stress. Glyoxalase-I (GLO-I) transgenic rats were used to explore whether overexpression of this MGO detoxifying enzyme reduces levels stress a rat model diabetes. Rats made streptozotocin, after 12 weeks, plasma multiple tissues isolated for analysis AGEs, carbonyl stress, GLO-I activity was significantly...

Blockade of angiotensin (Ang) II is efficient in various renal diseases. Although interest has focused on the hemodynamic changes and reduction proteinuria, recent studies emphasize nonhemodynamic effects Ang kidney injury. The aim this study was to clarify mechanisms immune system that alter balance helper T-cell (Th) subsets. We used a continuous, infusion model rats develop hypertension, tubulointerstitial damage, including de novo expression alpha-smooth muscle actin loss endothelial...

Abstract. Long-term peritoneal dialysis (PD) is associated with alterations in permeability and loss of ultrafiltration. These changes originate from increased surface area, but the morphologic molecular mechanisms involved remain unknown. The hypothesis that modifications activity and/or expression nitric oxide synthase (NOS) isozymes might play a role these modifications, via enhanced local production oxide, was tested this study. NOS activities were measured by L-citrulline assay biopsies...

Paroxysmal nocturnal hemoglobinuria (PNH) is a hemolytic disorder caused by deficiency of biosynthesis the glycosyl phosphatidylinositol (GPI) anchor, but biochemical defect not completely understood. In present study, we have analyzed affected cell lines established recently from two Japanese patients with PNH. Two evidence indicate that these cells do synthesize N-acetylglucosaminyl-phosphatidylinositol, first intermediate in GPI anchor biosynthesis. First, somatic hybridization analysis...

Impaired nitric oxide (NO)-dependent vasorelaxation plays a key role in the development of diabetic vascular complications. We investigated effect hyperglycaemia on impaired vasoreactivity and putative therein AGE precursor methylglyoxal. The effects high glucose methylglyoxal NO-dependent isolated rat mesenteric arteries from wild-type transgenic glyoxalase (GLO)-I (also known as GLO1) rats, i.e. enzyme detoxifying methylglyoxal, were recorded wire myograph. formation major...