Role of advanced glycation end products (AGEs) and their receptor (RAGE) in the pathogenesis of diabetic microangiopathy.
ABSTRACT Diabetic vascular complication is a leading cause of acquired blindness, end-stage renal failure, a variety of neuropathies and accelerated atherosclerosis, which could account for disabilities and high mortality rates in patients with diabetes. Chronic hyperglycemia is essentially involved in the pathogenesis of diabetic micro- and macrovascular complications via various metabolic derangements. In this review, we discuss the molecular mechanisms of diabetic retinopathy and nephropathy, especially focusing on advanced glycation end products (AGEs) and their receptor (RAGE) system. Several types of AGE inhibitors and their therapeutic implications in diseases, including diabetic microangiopathy, will be discussed in the next review article.
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ABSTRACT: Hemodialysis patients have an elevated genomic damage in peripheral blood lymphocytes (PBLs) and an increased cancer incidence, possibly due to accumulation of uremic toxins like advanced glycation end products (AGEs). Because the vitamin B1 prodrug benfotiamine reduces AGE levels in experimental diabetes, and dialysis patients often suffer from vitamin B1 deficiency, we conducted two consecutive studies supplementing hemodialysis patients with benfotiamine. In both studies, genomic damage was measured as micronucleus frequency of PBLs before and at three time-points after initiation of benfotiamine supplementation. AGE-associated fluorescence in plasma, and in the second study additionally, the antioxidative capacity of plasma was analyzed. Benfotiamine significantly lowered the genomic damage of PBLs in hemodialysis patients of both studies independent of changes in plasma AGE levels. The second study gave a hint to the mechanism, as the antioxidative capacity of the plasma of the treated patients clearly increased, which might ameliorate the DNA damage.Archiv für Experimentelle Pathologie und Pharmakologie 06/2008; 378(3):283-91. DOI:10.1007/s00210-008-0310-y · 2.36 Impact Factor
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ABSTRACT: Human serum albumin (HSA) is the most abundant protein in plasma, and plays multiple roles in physiology, including as a carrier protein for endogenous and exogenous compounds. Recent studies provide news evidences to support the enzymatic activities of HSA and new molecular insights for such activities. Here, the structural features and enzymatic characteristics of HSA are reviewed.Current Pharmaceutical Design 03/2015; 21(14). DOI:10.2174/1381612821666150302113906 · 3.29 Impact Factor
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ABSTRACT: Previous reports have suggested that advanced glycation end products (AGE) participate in the pathogenesis of diabetic macroangiopathy. However, current understanding of the mechanisms by which AGE may accelerate atherogenesis remains incomplete. Microarray and reverse transcription real-time PCR analyses revealed that exposure to AGE-BSA (BSA, bovine serum albumin) reduced mRNA levels (60%) in the ATP-binding cassette transporter G1 (ABCG1) but not ABCA1 in human macrophages. AGE-BSA also reduced ABCG1 protein levels. These effects occurred mainly through the receptor for AGE (RAGE), as an anti-RAGE antibody significantly limited ABCG1 mRNA reduction. Functional studies demonstrated that exposure to AGE-BSA decreased cholesterol efflux to high-density lipoprotein (HDL) (P<0.05) but not to apolipoprotein AI, compared to BSA treatment. Although liver X receptors (LXR) augment ABCG1 expression, macrophages treated with AGE-BSA showed no reduction in LXR mRNA levels or in the binding of nuclear proteins to the LXR response element, compared with BSA. Our data show that AGE-BSA can decrease cholesterol efflux from macrophages to HDL via an LXR-independent pathway. This novel mechanism may contribute to accelerated foam cell production and atherogenesis in diabetic patients.Atherosclerosis 06/2007; 192(2):298-304. DOI:10.1016/j.atherosclerosis.2006.07.023 · 3.97 Impact Factor