Methylglyoxal Drives a Distinct, Nonclassical Macrophage Activation Status

Metabolic complications in diabetic patients are driven by a combination of increased levels of nutrients and the presence of a proinflammatory environment. Methylglyoxal (MG) is a toxic byproduct of catabolism and has been strongly associated with the development of such complications. Macrophages are key mediators of inflammatory processes and their contribution to the development of metabolic complications has been demonstrated. However, a direct link between reactive metabolites and macrophage activation has not been demonstrated yet. Here, we show that acute MG treatment activated components of the p38 MAPK pathway and enhanced glycolysis in primary murine macrophages. MG induced a distinct gene expression profile sharing similarities with classically activated proinflammatory macrophages as well as metabolically activated macrophages usually found in obese patients. Transcriptomic analysis revealed a set of 15 surface markers specifically upregulated in MG-treated macrophages, thereby establishing a new set of targets for diagnostic or therapeutic purposes under high MG conditions, including diabetes. Overall, our study defines a new polarization state of macrophages that may specifically link aberrant macrophage activation to reactive metabolites in diabetes.

The Glyoxalase System—New Insights into an Ancient Metabolism

The glyoxalase system was discovered over a hundred years ago and since then it has been claimed to provide the role of an indispensable enzyme system in order to protect cells from a toxic byproduct of glycolysis. This review gives a broad overview of what has been postulated in the last 30 years of glyoxalase research, but within this context it also challenges the concept that the glyoxalase system is an exclusive tool of detoxification and that its substrate, methylglyoxal, is solely a detrimental burden for every living cell due to its toxicity. An overview of consequences of a complete loss of the glyoxalase system in various model organisms is presented with an emphasis on the role of alternative detoxification pathways of methylglyoxal. Furthermore, this review focuses on the overlooked posttranslational modification of Glyoxalase 1 and its possible implications for cellular maintenance under various (patho-)physiological conditions. As a final note, an intriguing point of view for the substrate methylglyoxal is offered, the concept of methylglyoxal (MG)-mediated hormesis.

Aerobic exercise and octopamine protect against deep-frying oil-induced cardiomyocyte apoptosis through modulation of caspase and pro-caspase 3

Background: Deep-frying is a common cooking method accompanied by production of carcinogenesis substance such as acrolein. Acrolein is a toxic byproduct of lipid peroxidation that is involved in the development of pulmonary, cardiac, and neurodegenerative diseases. This study aimed to explore the effect of aerobic exercise (EXE) and octopamine (OCT) on caspase 3 and pro-caspase 3 expression levels in the heart tissue of rats were fed deep-frying oil (DFO).Methods: 30 male Wistar rats were divided into 5 groups (n=6 in each) including 1) control (CO), 2) DFO, 3) DFO+EXE, 4) DFO+OCT and 5) DFO+EXE+OCT. The apoptotic effects of DFO on heart and cardiomyocytes’ fibers were examined by TUNEL assay and Masson's trichrome staining respectively. Also caspase 3 and pro-caspase 3 genes and proteins expression in all groups were evaluated using quantitative real-time PCR and western blotting method, respectively. Results: Data showed a significant increase in apoptotic cells in the DFO group (P <0.05). Masson's trichrome stain analysis demonstrated that the number of cardiomyocytes' fibers are decreased, and collagen deposition is increased in the DFO group. In comparison, the collagen percentage was significantly reduced in DFO+EXE, DFO +OCT and DFO+EXE+OCT groups. Also, the expression level of caspase 3 and pro-caspase 3 was significantly decreased in DFO+EXE+OCT group (P <0.05). Conclusions: The results of this study show that DFO lead to programmed cell death via the activation of caspases in heart tissue. However, it seems that aerobic exercise with octopamine supplementation improves heart tissue through decreasing in the expression of caspase 3 and pro-caspase 3 that inhibit apoptosis.

Aerobic exercise and octopamine protects against deep-frying oil-induced cardiomyocyte apoptosis through modulation of caspase and pro-caspase 3

Background : Deep-frying is a common cooking method in which cooking is accompanied by carcinogenic byproducts such as acrolein. Acrolein is a toxic byproduct of lipid peroxidation, which has been implicated in pulmonary, cardiac, and neurodegenerative diseases. This study aimed to explore the effect of aerobic exercise and octopamine on caspase 3 and pro-caspase 3 expression levels in the heart tissue of rat exposed deep-frying oil. Methods : 30 male Wistar rats were divided into 5 groups (n=6 in each) including 1) control (CO), 2) deep-frying oil (DFO), 3) deep-frying oil+exercise (DFO+EXE), 4) deep-frying oil+octopamine (DFO+OCT), and 5) deep-frying oil+exercise+octopamine (DFO+EXE+OCT). The apoptotic effects of DFO in heart tissue were examined by TUNEL assay. Masson's trichrome stain used to study cardiomyocytes’ fibers. Moreover, caspase 3 and pro-caspase 3 genes and proteins expression in all groups were evaluated using quantitative real-time PCR and western blotting method, respectively. Results : Data showed a significant increase in apoptotic cells in the DFO-treated group ( P <0.05). Masson's trichrome stain analysis demonstrated that the number of cardiomyocytes' fibers are decreased, and collagen deposition is increased in the DFO group. In comparison, the collagen percentage was significantly reduced in exercise, OCT, and exercise+OCT groups. Also, the expression level of caspase 3 and pro-caspase 3 was significantly decreased in deep-frying oil+exercise+OCT group ( P <0.05). Conclusions : The results of our study show that DFO lead to programmed cell death via the activation of caspase in heart tissue. However, it seems that aerobic exercise with octopamine supplementation improves heart tissue by significantly decrease the expression of caspase 3 and pro-caspase 3 that inhibit apoptosis.

Structural elucidation of a dual-activity PAP phosphatase-1 fromEntamoeba histolyticacapable of hydrolysing both 3′-phosphoadenosine 5′-phosphate and inositol 1,4-bisphosphate

The enzyme 3′-phosphoadenosine 5′-phosphatase-1 (PAP phosphatase-1) is a member of the Li+-sensitive Mg2+-dependent phosphatase superfamily, or inositol monophosphatase (IMPase) superfamily, and is an important regulator of the sulfate-activation pathway in all living organisms. Inhibition of this enzyme leads to accumulation of the toxic byproduct 3′-phosphoadenosine 5′-phosphate (PAP), which could be lethal to the organism. Genomic analysis ofEntamoeba histolyticasuggests the presence of two isoforms of PAP phosphatase. The PAP phosphatase-1 isoform of this organism is shown to be active over wide ranges of pH and temperature. Interestingly, this enzyme is inhibited by submillimolar concentrations of Li+, while being insensitive to Na+. Interestingly, the enzyme showed activity towards both PAP and inositol 1,4-bisphosphate and behaved as an inositol polyphosphate 1-phosphatase. Crystal structures of this enzyme in its native form and in complex with adenosine 5′-monophosphate have been determined to 2.1 and 2.6 Å resolution, respectively. The PAP phosphatase-1 structure is divided into two domains, namely α+β and α/β, and the substrate and metal ions bind between them. This is a first structure of any PAP phosphatase to be determined from a human parasitic protozoan. This enzyme appears to function using a mechanism involving three-metal-ion assisted catalysis. Comparison with other structures indicates that the sensitivity to alkali-metal ions may depend on the orientation of a specific catalytic loop.

Experimental Design and Study of Shear Technology for Biomass Comminuting

To increase the security of energy supply, it is essential to search for utilization alternatives of renewable energy sources. The fermentation of organic material is more effective if the substrate is subjected to pre-treatment. In order to avoid toxic byproduct in the course of pre-treatment, a mechanical method was preferred. In this paper, the behavior of agricultural raw materials subjected to mechanical disintegration is examined. The pre-treatment of substrate was carried out with a comminuting machine which is normally used in industrial sewage fermenters in Hungary, but in agricultural biogas plants it has not been built in the technological process yet.