Preconditioning with Maillard reaction products improves antioxidant defence leading to increased stress tolerance in cardiac cells

Advanced glycation end products (AGEs) are considered as biomarkers of ageing and are associated with several degenerative diseases. Besides endogenous formation, significant amounts of AGEs are taken up with food. Although nutritional AGEs are considered as undesirable, proinflammatory agents, they may also enclose potentially beneficial antioxidants. We used rodent cardiac cells to evaluate if food AGEs, present in bread crust, can modify the cellular antioxidant defence. Mice were fed with bread crust containing diet to prove the in-vivo relevance for the heart. In mouse cardiac fibroblasts, bread crust extract induced a moderate elevation of ROS production causing an activation of p42/p44^MAPK, p38^MAPK and NF-κB, followed by increased expression of antioxidative enzymes. Preconditioning studies demonstrated that this was sufficient to protect cardiac fibroblasts and rat adult cardiac myocytes against severe oxidative stress. Furthermore, mice, fed a bread crust containing diet, exhibited a similarly improved cardiac expression of antioxidative defence genes. The consumption of AGEs can therefore contribute to an improved antioxidant status of the heart, thus exhibiting cardioprotective effects in case of severe oxidative stress as in ischemia reperfusion injury. Also, these data show that the exclusive interpretation of circulating AGEs as pathophysiological biomarkers of ageing might be misleading.     

The metabolic enhancer piracetam ameliorates the impairment of mitochondrial function and neurite outgrowth induced by ?-amyloid peptide

Background and purpose:

β-Amyloid peptide (Aβ) is implicated in the pathogenesis of Alzheimer''s disease by initiating a cascade of events from mitochondrial dysfunction to neuronal death. The metabolic enhancer piracetam has been shown to improve mitochondrial dysfunction following brain aging and experimentally induced oxidative stress.

Experimental approach:

We used cell lines (PC12 and HEK cells) and murine dissociated brain cells. The protective effects of piracetam in vitro and ex vivo on Aβ-induced impairment of mitochondrial function (as mitochondrial membrane potential and ATP production), on secretion of soluble Aβ and on neurite outgrowth in PC12 cells were investigated.

Key results:

Piracetam improves mitochondrial function of PC12 cells and acutely dissociated brain cells from young NMRI mice following exposure to extracellular Aβ_1-42. Similar protective effects against Aβ_1-42 were observed in dissociated brain cells from aged NMRI mice, or mice transgenic for mutant human amyloid precursor protein (APP) treated with piracetam for 14 days. Soluble Aβ load was markedly diminished in the brain of those animals after treatment with piracetam. Aβ production by HEK cells stably transfected with mutant human APP was elevated by oxidative stress and this was reduced by piracetam. Impairment of neuritogenesis is an important consequence of Aβ-induced mitochondrial dysfunction and Aβ-induced reduction of neurite growth in PC12 cells was substantially improved by piracetam.

Conclusion and implications:

Our findings strongly support the concept of improving mitochondrial function as an approach to ameliorate the detrimental effects of Aβ on brain function.This article is commented on by Moncada, pp. 217–219 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2010.00706.x and to view related papers by Pravdic et al. and Puerta et al. visit http://dx.doi.org/10.1111/j.1476-5381.2010.00698.x and http://dx.doi.org/10.1111/j.1476-5381.2010.00663.x     

Enhanced apoptosis, oxidative stress and mitochondrial dysfunction in lymphocytes as potential biomarkers for Alzheimer's disease

Alzheimer's disease (AD) is the most common progressive neurodegenerative disease. Today, AD affects millions of people worldwide and the number of AD cases will increase with increased life expectancy. The AD brain is marked by severe neurodegeneration like the loss of synapses and neurons, atrophy and depletion of neurotransmitter systems in the hippocampus and cerebral cortex. Recent findings suggest that these pathological changes are causally induced by mitochondrial dysfunction, increased oxidative stress and elevated apoptosis. Until now, AD cannot be diagnosed by a valid clinical method or a biomarker before the disease has progressed so far that dementia is present. Furthermore, no valid method is available to determine which patient with mild cognitive impairment (MCI) will progress to AD. Therefore, a correct diagnosis in the early stage of AD is not only of importance considering that early drug treatment is more effective but also that the psychological burden of the patients and relatives could be decreased. In this review, we discuss the potential role of elevated apoptosis, increased oxidative stress and mitochondrial dysfunction as biomarker for AD in a peripheral cell model, the lymphocytes.     

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