Aminoguanidine and metformin prevent the reduced rate of HDL-mediated cell cholesterol efflux induced by formation of advanced glycation end products

2006 ◽  
Vol 38 (3) ◽  
pp. 392-403 ◽  
Author(s):  
Adriana P. Machado ◽  
Raphael S. Pinto ◽  
Zenaide P. Moysés ◽  
Edna R. Nakandakare ◽  
Eder C.R. Quintão ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Cholesterol Efflux ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Reduced Rate

scholarly journals 3: INHIBITION OF THE RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS RESTORES CHOLESTEROL EFFLUX IN THP-1 HUMAN MACROPHAGES EXPOSED TO PLASMA FROM TYPE 1 DIABETES MELLITUS PATIENTS

2016 ◽  
Vol 64 (3) ◽  
pp. 800.3-800
Author(s):  
JM Corletto ◽  
S Accacha ◽  
I Voloshyna ◽  
N Siegart ◽  
L Kasselman ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Advanced Glycation End Products ◽  
Cholesterol Efflux ◽  
Mrna Level ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
Abca1 Expression ◽  
End Products ◽  
Efflux Proteins

Purpose of StudyAdvanced glycation end products (AGE), proteins formed by nonenzymatic glycation, are prevalent in patients with diabetes mellitus (DM) and contribute to the development of atherosclerosis. We have demonstrated that plasma from patients with type 1 DM (T1DM) decreases expression of cholesterol efflux proteins in cultured THP-1 macrophages compared to healthy control (HC) plasma. Here we explore a mechanism that restores cholesterol efflux in T1DM plasma through blockade of the receptor for AGE (RAGE).Methods UsedCarboxy-methyl-lysine-modified proteins (CML-MP), the most prevalent AGE in vivo, were measured in the plasma of 20 pediatric T1DM patients and 20 sex and age-matched HC by ELISA. THP-1 macrophages (106/ml) were incubated for 18 h in RPMI media in the presence of 10% plasma from each enrolled patient in triplicate±anti-RAGE antibody. Cholesterol efflux proteins: ATP binding cassette transporter (ABC)A1 and 27-hydroxylase were quantified by real-time RT-PCR using specific primers for each gene.Summary of ResultsThe level of CML-MP was significantly elevated in T1DM plasma (1.65±1.3 ng/ml) versus HC plasma (1.05±0.4 ng/ml) (P<0.05, n=20). ABCA1 expression was significantly lower in macrophages exposed to T1DM plasma (1.108±0.8 U) versus HC plasma (1.624±0.6) (P<0.05, n=20). Exposure of THP-1 macrophages to T1DM plasma downregulated 27-hydroxylase mRNA to 1.94±0.9 U in T1DM versus 3.4±2.9 U in HC (P<0.01, n=20). Inactivation of RAGE before exposure to T1DM plasma increased ABCA1 expression by 20%. However, we observed no effect on the level of 27-hydroxylase.ConclusionsWe demonstrate that elevated AGE in plasma of T1DM patients inhibits cholesterol efflux and suppresses intracellular cholesterol processing via 27-hydroxylase and ABCA1 in naïve macrophages. RAGE inactivation restores mRNA level of the ABCA1 transporter, but not the 27-hydroxylase enzyme. These findings impart new targets for prevention of cardiovascular disease in DM and suggest that factors other than AGE may impact cholesterol transport.

scholarly journals Update on Mechanisms of Renal Tubule Injury Caused by Advanced Glycation End Products

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Hong Sun ◽  
Yang Yuan ◽  
Zilin Sun
Keyword(s):  
Advanced Glycation End Products ◽  
Lipid Accumulation ◽  
Cholesterol Efflux ◽  
Cholesterol Synthesis ◽  
Renal Tubule ◽  
Foam Cell Formation ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Renal Tubular

Diabetic nephropathy (DN) caused by advanced glycation end products (AGEs) may be associated with lipid accumulation in the kidneys. This study was designed to investigate whether Nε-(carboxymethyl) lysine (CML, a member of the AGEs family) increases lipid accumulation in a human renal tubular epithelial cell line (HK-2) via increasing cholesterol synthesis and uptake and reducing cholesterol efflux through endoplasmic reticulum stress (ERS). Our results showed that CML disrupts cholesterol metabolism in HK-2 cells by activating sterol regulatory element-binding protein 2 (SREBP-2) and liver X receptor (LXR), followed by an increase in 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR) mediated cholesterol synthesis and low density lipoprotein receptor (LDLr) mediated cholesterol uptake and a reduction in ATP-binding cassette transporter A1 (ABCA1) mediated cholesterol efflux, ultimately causing lipid accumulation in HK-2 cells. All of these responses could be suppressed by an ERS inhibitor, which suggests that CML causes lipid accumulation in renal tubule cells through ERS and that the inhibition of ERS is a potential novel approach to treating CML-induced renal tubular foam cell formation.

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