Early energy metabolism-related molecular events in skeletal muscle of diabetic rats: The effects of l -arginine and SOD mimic

Considering the vital role of skeletal muscle in control of whole-body metabolism and the severity of long-term diabetic complications, we aimed to reveal the molecular pattern of early diabetes-related skeletal muscle phenotype in terms of energy metabolism, focusing on regulatory mechanisms, and the possibility to improve it using two redox modulators, L-arginine and superoxide dismutase (SOD) mimic. Alloxan-induced diabetic rats (120 mg/kg) were treated with L-arginine or the highly specific SOD mimic, M40403, for 7 days. As appropriate controls, non-diabetic rats received the same treatments. We found that L-arginine and M40403 restored diabetes-induced impairment of phospho-5′-AMP-activated protein kinase α (AMPKα) signaling by upregulating AMPKα protein itself and its downstream effectors, peroxisome proliferator-activated receptor-γ coactivator-1α and nuclear respiratory factor 1. Also, there was a restitution of the protein levels of oxidative phosphorylation components (complex I, complex II and complex IV) and mitofusin 2. Furthermore, L-arginine and M40403 induced translocation of glucose transporter 4 to the membrane and upregulation of protein of phosphofructokinase and acyl coenzyme A dehydrogenase, diminishing negative diabetic effects on limiting factors of glucose and lipid metabolism. Both treatments abolished diabetes-induced downregulation of sarcoplasmic reticulum calcium-ATPase proteins (SERCA 1 and 2). Similar effects of L-arginine and SOD mimic treatments suggest that disturbances in the superoxide/nitric oxide ratio may be responsible for skeletal muscle mitochondrial and metabolic impairment in early diabetes. Our results provide evidence that L-arginine and SOD mimics have potential in preventing and treating metabolic disturbances accompanying this widespread metabolic disease.Chemico-Biological Interactions (2017), 272: 188-19

Etude d'échange de solvant sur des composés demi- sandwich du Ru(II) et sur Rh24+

Hippocampal structural changes associated with diabetes-related cognitive impairments are well described, but their molecular background remained vague. We examined whether/how diabetes alters molecular basis of energy metabolism in hippocampus readily after diabetes onset, with special emphasis on its redox-sensitivity. To induce diabetes, adult Mill Hill hybrid hooded rats received a single alloxan dose (120 mg/kg). Both non-diabetic and diabetic groups were further divided in two subgroups receiving (i) or not (ii) superoxide dismutase (SOD) mimic, [Mn(II)(pyane)Cl-2] for 7 days, i.p. Treatment of the diabetic animals started after blood glucose level >= 12 mM. Diabetes decreased protein levels of oxidative phosphorylation components: complex III and ATP synthase. In contrast, protein amounts of glyceraldehyde-3-phosphate dehydrogenase, pyruvate dehydrogenase, and hypoxia-inducible factor-1 alpha - the key regulator of energy metabolism in stress conditions, were higher in diabetic animals. Treatment with SOD mimic restored/increased the levels of oxidative phosphorylation components and returned hypoxia-inducible factor-1 alpha to control level, while diabetes-induced up-regulation of glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase, was additionally stimulated. To conclude, our results provide insight into the earliest molecular changes of energy-producing pathways in diabetes that may account for structural/functional disturbance of hippocampus, seen during disease progression. Also, data suggest [Mn(II)(pyane)Cl-2] as potential therapeutic agent in cutting-edge approaches to threat this widespread metabolic disorder. (C) 2013 Elsevier Inc. All rights reserved.Ministry of Education, Science and Technological Development of the Republic of Serbia [173054, 173055

The effects of superoxide dismutase mimic on energy metabolism in hippocampus of diabetic rats

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The effects of superoxide dismutase mimic on energy metabolism in hippocampus of diabetic rats

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Manganese (II) pentaazamacrocyclic SOD mimic improves functional status of human sperm mitochondria: involvement of iNO

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Is Manganese (II) Pentaazamacrocyclic Superoxide Dismutase Mimic Beneficial for Human Sperm Mitochondria Function and Motility?

Mitochondria play an important role in sperm cell maturation and function. Here, we examined whether (and how) changes in sperm redox milieu affect the functional status of sperm mitochondria, that is, sperm functionality. Compared with the control, incubation in Tyrode's medium for 3 h, under noncapacitating conditions, decreased sperm motility, the amount of nitric oxide ((NO)-N-center dot), the number of MitoTracker (R) Green FM (MT-G) positive mitochondria, and the expression of complexes I and IV of the mitochondrial respiratory chain. In turn, superoxide dismutase (SOD) mimic (M40403) treatment restored/increased these parameters, as well as the expression of endothelial nitric oxide synthase, manganese SOD, and catalase. These data lead to the hypothesis that M40403 improves mitochondrial functional state and motility of spermatozoa, as well as (NO)-N-center dot might be involved in the observed effects of the mimic. Antioxid. Redox Signal. 18, 170-178.Ministry of Education and Science of the Republic of Serbia [173054]; University of Erlangen-Nurember

Manganese (II) pentaazamacrocyclic SOD mimic improves functional status of human sperm mitochondria: involvement of iNO

nul

Is Manganese (II) Pentaazamacrocyclic Superoxide Dismutase Mimic Beneficial for Human Sperm Mitochondria Function and Motility?

Mitochondria play an important role in sperm cell maturation and function. Here, we examined whether (and how) changes in sperm redox milieu affect the functional status of sperm mitochondria, that is, sperm functionality. Compared with the control, incubation in Tyrode's medium for 3 h, under noncapacitating conditions, decreased sperm motility, the amount of nitric oxide ((NO)-N-center dot), the number of MitoTracker (R) Green FM (MT-G) positive mitochondria, and the expression of complexes I and IV of the mitochondrial respiratory chain. In turn, superoxide dismutase (SOD) mimic (M40403) treatment restored/increased these parameters, as well as the expression of endothelial nitric oxide synthase, manganese SOD, and catalase. These data lead to the hypothesis that M40403 improves mitochondrial functional state and motility of spermatozoa, as well as (NO)-N-center dot might be involved in the observed effects of the mimic. Antioxid. Redox Signal. 18, 170-178.Ministry of Education and Science of the Republic of Serbia [173054]; University of Erlangen-Nurember