Modulation of amyloid beta peptide(1-42) cytotoxicity and aggregation in vitro by glucose and chondroitin sulfate.

One mechanism leading to neurodegeneration during Alzheimer's disease (AD) is amyloid beta peptide (Abeta)-induced neurotoxicity. Among the factors proposed to potentiate Abeta toxicity is its covalent modification through carbohydrate-derived advanced glycation endproducts (AGEs). Other experimental evidence, though, indicates that certain polymeric carbohydrates like the glycosaminoglycan (GAG) chains found in proteoglycan molecules attenuate the neurotoxic effect of Abeta in primary neuronal cultures. Pretreatment of the 42-residue Abeta fragment (Abeta1-42) with the ubiquitous brain carbohydrates, glucose, fructose, and the GAG chondroitin sulfate B (CSB) inhibits Abeta1-42-induced apoptosis and reduces the peptide neurotoxicity on neuroblastoma cells, a cytoprotective effect that is partially reverted by AGE inhibitors such as pyridoxamine and L-carnosine. Thioflavin T fluorescence measurements indicate that at concentrations close to physiological, only CSB promotes the formation of Abeta amyloid fibril structure. Atomic force microscopy imaging and Western blot analysis suggest that glucose favours the formation of globular oligomeric structures derived from aggregated species. Our data suggest that at short times carbohydrates reduce Abeta1-42 toxicity through different mechanisms both dependent and independent of AGE formation.

Effect of the nucleotides CMP and UMP on exhaustion in exercise rats.

The aetiology of muscle fatigue has yet not been clearly established. Administration of two nucleotides, cytosine monophosphate (CMP) and uridine monophosphate (UMP), has been prescribed for the treatment of neuromuscular affections in humans. Patients treated with CMP/UMP recover from altered neurological functions and experience pain relief, thus the interest to investigate the possible effect of the drug on exhausting exercise. With such aim, we have determined, in exercised rats treated with CMP/UMP, exercise endurance, levels of lactate, glucose and glycogen, and the activity of several metabolic enzymes such as, creatine kinase (CK), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST). Our results show that rats treated with CMP/UMP are able to endure longer periods of exercise (treadmill-run). Before exercise, muscle glucose level is significantly higher in treated rats, suggesting that the administration of CMP/UMP favours the entry of glucose in the muscle. Liver glycogen levels remains unaltered during exercise, suggesting that CMP/UMP may be implicated in maintaining the level of hepatic glycogen constant during exercise. Lactate dehydrogenase and aspartate aminotransferase activity is significantly lower in the liver of treated rats. These results suggest that administration of CMP/UMP enable rats to endure exercise by altering some metabolic parameters.

Effect of the nucleotides CMP and UMP on exhaustion in exercise rats

The aetiology of muscle fatigue has yet not been clearly established. Administrationof two nucleotides, cytosine monophosphate (CMP) and uridine monophosphate(UMP), has been prescribed for the treatment of neuromuscular affections inhumans. Patients treated with CMP/UMP recover from altered neurological functionsand experience pain relief, thus the interest to investigate the possible effect ofthe drug on exhausting exercise. With such aim, we have determined, in exercised ratstreated with CMP/UMP, exercise endurance, levels of lactate, glucose and glycogen,and the activity of several metabolic enzymes such as, creatine kinase (CK), lactatedehydrogenase (LDH), and aspartate aminotransferase (AST). Our results show thatrats treated with CMP/UMP are able to endure longer periods of exercise (treadmillrun).Before exercise, muscle glucose level is significantly higher in treated rats, suggestingthat the administration of CMP/UMP favours the entry of glucose in themuscle. Liver glycogen levels remains unaltered during exercise, suggesting thatCMP/UMP may be implicated in maintaining the level of hepatic glycogen constantduring exercise. Lactate dehydrogenase and aspartate aminotransferase activity is significantlylower in the liver of treated rats. These results suggest that administrationof CMP/UMP enable rats to endure exercise by altering some metabolic parameters (AU)

No dipsonible