390 research outputs found

    Deletion of RAGE fails to prevent hepatosteatosis in obese mice due to impairment of other AGEs receptors and detoxifying systems

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    Advanced glycation endproducts (AGEs) are involved in several diseases, including NAFLD and NASH. RAGE is the main receptor mediating the pro-inflammatory signalling induced by AGEs. Therefore, targeting of RAGE has been proposed for prevention of chronic inflammatory diseases. However, the role of RAGE in the development of NAFLD and NASH remains poorly understood. We thus aimed to analyse the effect of obesity on AGEs accumulation, AGE-receptors and AGE-detoxification, and whether the absence of RAGE might improve hepatosteatosis and inflammation, by comparing the liver of lean control, obese (LeptrDb−/−) and obese RAGE-deficient (RAGE−/− LeptrDb−/−) mice. Obesity induced AGEs accumulation and RAGE expression with hepatosteatosis and inflammation in LeptrDb−/−, compared to lean controls. Despite the genetic deletion of RAGE in the LeptrDb−/− mice, high levels of intrahepatic AGEs were maintained accompanied by decreased expression of the protective AGE-receptor-1, impaired AGE-detoxifying system glyoxalase-1, and increased expression of the alternative AGE-receptor galectin-3. We also found sustained hepatosteatosis and inflammation as determined by persistent activation of the lipogenic SREBP1c and proinflammatory NLRP3 signalling pathways. Thus, RAGE targeting is not effective in the prevention of NAFLD in conditions of obesity, likely due to the direct liver specific crosstalk of RAGE with other AGE-receptors and AGE-detoxifying systems

    Deletion of RAGE fails to prevent hepatosteatosis in obese mice due to impairment of other AGEs receptors and detoxifying systems

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    Abstract Advanced glycation endproducts (AGEs) are involved in several diseases, including NAFLD and NASH. RAGE is the main receptor mediating the pro-inflammatory signalling induced by AGEs. Therefore, targeting of RAGE has been proposed for prevention of chronic inflammatory diseases. However, the role of RAGE in the development of NAFLD and NASH remains poorly understood. We thus aimed to analyse the effect of obesity on AGEs accumulation, AGE-receptors and AGE-detoxification, and whether the absence of RAGE might improve hepatosteatosis and inflammation, by comparing the liver of lean control, obese (LeptrDb−/−) and obese RAGE-deficient (RAGE−/− LeptrDb−/−) mice. Obesity induced AGEs accumulation and RAGE expression with hepatosteatosis and inflammation in LeptrDb−/−, compared to lean controls. Despite the genetic deletion of RAGE in the LeptrDb−/− mice, high levels of intrahepatic AGEs were maintained accompanied by decreased expression of the protective AGE-receptor-1, impaired AGE-detoxifying system glyoxalase-1, and increased expression of the alternative AGE-receptor galectin-3. We also found sustained hepatosteatosis and inflammation as determined by persistent activation of the lipogenic SREBP1c and proinflammatory NLRP3 signalling pathways. Thus, RAGE targeting is not effective in the prevention of NAFLD in conditions of obesity, likely due to the direct liver specific crosstalk of RAGE with other AGE-receptors and AGE-detoxifying systems

    Highly-efficient N-arylation of imidazole catalyzed by Cu(II) complexes with quaternary ammonium-functionalized 2-acetylpyridine acylhydrazone

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    The reaction of (E)-N,N,N-trimethyl-2-oxo-2-(2-(1-(pyridin-2-yl)ethylidene)hydrazinyl)ethan-1-aminium-chloride (HLCl) with copper(II) perchlorate led to mononuclear [CuLCl]ClO 4 complex (1). The same reaction with excess of sodium azide gives dinuclear azido double end-on bridged Cu(II) complex [Cu 2 L 2 (μ- 1,1 -N 3 ) 2 ](ClO 4 ) 2 (2). In both complexes hydrazone ligand is NNO coordinated in monodeprotonated formally neutral zwitter-ionic form. Complexes were characterized by elemental analysis, IR spectroscopy and single-crystal X-ray crystallography. Variable‐temperature magnetic susceptibility measurements for dinuclear Cu(II) complex showed intra-dimer ferromagnetic coupling between Cu(II) ions (J = 7.4 cm −1 ). DFT-BS calculations provided explanation for magnetic properties of dinuclear Cu(II) complex. Both complexes were shown to highly efficiently catalyze the N-arylation of imidazole and benzimidazole with electron-poor or electron-rich aryl iodides, under user-friendly and sustainable conditions.This is the peer-reviewed version of the following article: Milenković, M. R.; Papastavrou, A. T.; Radanović, D.; Pevec, A.; Jagličić, Z.; Zlatar, M.; Gruden, M.; Vougioukalakis, G. C.; Turel, I.; Anđelković, K.; et al. Highly-Efficient N-Arylation of Imidazole Catalyzed by Cu(II) Complexes with Quaternary Ammonium-Functionalized 2-Acetylpyridine Acylhydrazone. Polyhedron 2019, 165, 22–30. [https://doi.org/10.1016/j.poly.2019.03.001]Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/3006
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