Oxidative Stress Markers and Na,K-ATPase Enzyme Kinetics Are Altered in the Cerebellum of Zucker Diabetic Fatty fa/fa Rats: A Comparison with Lean fa/+ and Wistar Rats.

Type 2 diabetes mellitus has been referred to as being closely related to oxidative stress, which may affect brain functions and brain glucose metabolism due to its high metabolic activity and lipid-rich content. Na,K-ATPase is an essential enzyme maintaining intracellular homeostasis, with properties that can sensitively mirror various pathophysiological conditions such as diabetes. The goal of this study was to determine oxidative stress markers as well as Na,K-ATPase activities in the cerebellum of Zucker diabetic fatty (ZDF) rats depending on diabetes severity.

Na,K-ATPase Kinetics and Oxidative Stress in Kidneys of Zucker Diabetic Fatty (fa/fa) Rats Depending on the Diabetes Severity-Comparison with Lean (fa/+) and Wistar Rats.

For a better insight into relations between type 2 diabetes mellitus (T2DM) and Na,K-ATPase properties in kidneys, we aimed to characterize two subgroups of ZDF obese (fa/fa) rats, with more and less developed T2DM, and compare them with two controls: lean (fa/+) and Wistar. Na,K-ATPase enzyme kinetics were estimated by measuring the ATP hydrolysis in the range of NaCl and ATP levels. As Na,K-ATPase is sensitive to oxidative stress, we evaluated selected oxidative stress parameters in kidney homogenates.

ZDF (fa/fa) rats show increasing heterogeneity in main parameters during ageing, as confirmed by biometrics, oxidative stress markers and MMP activity.

New Findings: What is the central question of this study? The aim was to characterize Zucker diabetic fatty [ZDF (fa/fa)] rats and two control strains [Wistar and lean ZDF (fa/+) rats] during ageing. What is the main finding and its importance? Zucker diabetic fatty (fa/fa) rats with lower glycaemia have higher body and left ventricular weights and lower plasma gelatinase activity compared with hyperglycaemic rats. Given that type 2 diabetes is a heterogeneous metabolic disorder, the inhomogeneity of ZDF (fa/fa) rats might be beneficial in the study of its different aspects.

Toward the Decipherment of Molecular Interactions in the Diabetic Brain.

Diabetes mellitus (DM) has been associated with cognitive complications in the brain resulting from acute and chronic metabolic disturbances happening peripherally and centrally. Numerous studies have reported on the morphological, electrophysiological, biochemical, and cognitive changes in the brains of diabetic individuals. The detailed pathophysiological mechanisms implicated in the development of the diabetic cognitive phenotype remain unclear due to intricate molecular changes evolving over time and space.

Global brain ischemia in rats is associated with mitochondrial release and downregulation of Mfn2 in the cerebral cortex, but not the hippocampus.

Mitochondria are crucial for neuronal cell survival and death through their functions in ATP production and the intrinsic pathway of apoptosis. Mitochondrial dysfunction is considered to play a central role in several serious human diseases, including neurodegenerative diseases, such as Parkinson's and Alzheimer's disease and ischemic neurodegeneration. The aim of the present study was to investigate the impact of transient global brain ischemia on the expression of selected proteins involved in mitochondrial dynamics and mitochondria‑associated membranes.

Diabetes-induced abnormalities of mitochondrial function in rat brain cortex: the effect of n-3 fatty acid diet.

Diabetic encephalopathy, a proven complication of diabetes is associated with gradually developing end-organ damage in the CNS increasing the risk of stroke, cognitive dysfunction or Alzheimer's disease. This study investigated the response of rat cortical mitochondria to streptozotocin-induced diabetes and the potential for fish oil emulsion (FOE) to modulate mitochondrial function. Diabetes-induced deregulation of the respiratory chain function as a result of diminished complex I activity (CI) and cytochrome c oxidase hyperactivity was associated with attenuation of antioxidant defense of isolated cortical mitochondria, monitored by SOD activity, the thiol content, the dityrosine and protein-lipid peroxidation adduct formation.

Oxidative Stress Markers and Their Dynamic Changes in Patients after Acute Ischemic Stroke.

We have focused on determining the range of oxidative stress biomarkers and their dynamic changes in patients at different time points after the acute ischemic stroke (AIS). 82 patients with AIS were involved in our study and were tested: within 24 h from the onset of the attack (group A); at 7-day follow-up (group B); and at 3-month follow-up (group C). 81 gender and age matched volunteers were used as controls.

Look into brain energy crisis and membrane pathophysiology in ischemia and reperfusion.

In an ischemic environment, brain tissue responds to oxygen deprivation with the initiation of rapid changes in bioenergetic metabolism to ensure ion and metabolic homeostasis. At the same time, the accelerated cleavage of membrane phospholipids changes membrane composition and increases free fatty acid concentration. Phospholipid breakdown also generates specific messengers that participate in signaling cascades that can either promote neuronal protection or cause injury.

Possible contribution of proteins of Bcl-2 family in neuronal death following transient global brain ischemia.

Proteins of Bcl-2 family are crucial regulators of intrinsic (mitochondrial) pathway of apoptosis that is implicated among the mechanisms of ischemic neuronal death. Initiation of mitochondrial apoptosis depends on changes of equilibrium between anti-apoptotic and pro-apoptotic proteins of Bcl-2 family as well as on translocation of pro-apoptotic proteins of Bcl-2 family to mitochondria. The aim of this work was to study the effect of transient global brain ischemia on expression and intracellular distribution of proteins of Bcl-2 family in relation to the ischemia-induced changes of ERK and Akt kinase pathways as well as disturbances in ubiquitin proteasome system.

Ischemia-induced inhibition of mitochondrial complex I in rat brain: effect of permeabilization method and electron acceptor.

In this study we have examined the effect of global brain ischemia/reperfusion on biochemical properties of the mitochondrial respiratory complex I (CI) in rat hippocampus and cortex. Since the inner mitochondrial membrane forms the permeability barrier for NADH, the methodology of enzymatic activity determinations employs membrane permeabilization methods. This action affects the basic character of electrostatic and hydrophobic interactions inside the membrane and might influence functional properties of membrane embedded proteins.

Leptin, adiponectin and ghrelin, new potential mediators of ischemic stroke.

Objectives: Fat tissue is an important endocrine organ that produces a number of hormones and cytokines (leptin, adiponectin, resistin, plasminogen activator inhibitor-1, Tumour necrosis factor TNF α) with essential roles in regulation of many physiological functions.

Methods: We targeted implications of adipokines in ischemic stroke patients. Patients with acute stroke were examined (n=145) and the results were compared with the control group (n=68).

Mitochondrial complex I in the network of known and unknown facts.

The mitochondrial respiratory chain consists of five multi-subunit complexes embedded in the inner mitochondrial membrane. Complex I is the largest and most complicated proton pump of the respiratory chain encoded by both the mitochondrial and nuclear genomes. In this minireview, attention is given to recent knowledge on the structure, catalytic properties, supramolecular organisation of complex I and its possible role in the triggering of apoptosis.

Cross-talk of intracellular calcium stores in the response to neuronal ischemia and ischemic tolerance.

Ischemic/reperfusion brain injury (IRI) is a very severe event with the multiple etiopathogenesis. Ischemic preconditioning (IPC) is an important phenomenon of adaptation of CNS to subsequent ischemia. An altered cross-talk between intracellular calcium stores is presumed in the mechanisms of ischemic damage/protection.

Ischemia-induced mitochondrial apoptosis is significantly attenuated by ischemic preconditioning.

Ischemic preconditioning (IPC) represents an important adaptation of CNS to sub-lethal ischemia, which results in increased tolerance of CNS to the lethal ischemia. Ischemia-induced mitochondrial apoptosis is considered to be an important event leading to neuronal cell death after cerebral blood flow arrest. In presented study, we have determined the effect of IPC on ischemia/reperfusion-induced mitochondrial apoptosis.

Mitochondrial calcium transport and mitochondrial dysfunction after global brain ischemia in rat hippocampus.

Here we report effect of ischemia-reperfusion on mitochondrial Ca2+ uptake and activity of complexes I and IV in rat hippocampus. By performing 4-vessel occlusion model of global brain ischemia, we observed that 15 min ischemia led to significant decrease of mitochondrial capacity to accumulate Ca2+ to 80.8% of control whereas rate of Ca2+ uptake was not significantly changed.