Protein antioxidant response to the stress and the relationship between molecular structure and antioxidant function.

BACKGROUND: Proteins have long been considered a principal target for oxidants as a result of their abundance in biological systems. However, there is increasing evidence about the significant antioxidant activity in proteins such as albumin. It is leading to new concepts that even consider albumin not only as an antioxidant but as the major antioxidant in plasma known to be exposed to continuous oxidative stress. Evidence presented here establishes a previously unrecognized relationship between proteins' antioxidant capacity and structural stress. METHODOLOGY/PRINCIPAL FINDINGS: A chemiluminiscence based antioxidant assay was achieved to quantify the antioxidant capacity of albumin and other proteins. The capabilities of proteins as antioxidants were presented, but in addition a new and powerful component of the protein antioxidant capacity was discovered. The intrinsic component, designated as Response Surplus (RS), represents a silent reserve of antioxidant power that awakens when proteins face a structural perturbation (stressor) such as temperature, short wave UV light, the same reactive oxygen species, and more extreme changes like glucose or aldehyde-mediated structural modifications. The work also highlights the importance of structural changes in protein antioxidant properties and the participation of sulfhydryl groups (SHs) in the RS antioxidant component. Based on recent evidence about the SH group chemistry, a possible model for explaining RS is proposed. CONCLUSIONS/SIGNIFICANCE: The data presented show the significant antioxidant behavior of proteins and demonstrate the existence of a previously unrecognized antioxidant response to the stress. Several implications, including changes in elementary concepts about antioxidants and protein function, should emerge from here.

Glucose-6-phosphate dehydrogenase activity and NADPH/NADP+ ratio in liver and pancreas are dependent on the severity of hyperglycemia in rat.

Hyperglycemia is associated with metabolic disturbances affecting cell redox potential, particularly the NADPH/NADP+ ratio and reduced glutathione levels. Under oxidative stress, the NADPH supply for reduced glutathione regeneration is dependent on glucose-6-phosphate dehydrogenase. We assessed the effect of different hyperglycemic conditions on enzymatic activities involved in glutathione regeneration (glucose-6-phosphate dehydrogenase and glutathione reductase), NADP(H) and reduced glutathione concentrations in order to analyze the relative role of these enzymes in the control of glutathione restoration. Male Sprague-Dawley rats with mild, moderate and severe hyperglycemia were obtained using different regimens of streptozotocin and nicotinamide. Fifteen days after treatment, rats were killed and enzymatic activities, NADP(H) and reduced glutathione were measured in liver and pancreas. Severe hyperglycemia was associated with decreased body weight, plasma insulin, glucose-6-phosphate dehydrogenase activity, NADPH/NADP+ ratio and glutathione levels in the liver and pancreas, and enhanced NADP+ and glutathione reductase activity in the liver. Moderate hyperglycemia caused similar changes, although body weight and liver NADP+ concentration were not affected and pancreatic glutathione reductase activity decreased. Mild hyperglycemia was associated with a reduction in pancreatic glucose-6-phosphate dehydrogenase activity. Glucose-6-phosphate dehydrogenase, NADPH/NADP+ ratio and glutathione level, vary inversely in relation to blood glucose concentrations, whereas liver glutathione reductase was enhanced during severe hyperglycemia. We conclude that glucose-6-phosphate dehydrogenase and NADPH/NADP+ were highly sensitive to low levels of hyperglycemia. NADPH/NADP+ is regulated by glucose-6-phosphate dehydrogenase in the liver and pancreas, whereas levels of reduced glutathione are mainly dependent on the NADPH supply.

Diabetogenic effect of STZ diminishes with the loss of nitric oxide: role of ultraviolet light and carboxy-PTIO.

Nitric oxide has been demonstrated to participate in beta-cell damage during streptozotocin (STZ)-induced diabetes. STZ consists of 2-deoxy-D-glucose substituted by N-methyl-N-nitrosourea at C-2 and therefore can liberate (.) NO. However, it has not been proven whether (.) NO generation from STZ is responsible for the disease. We found that STZ treated in vitro with ultraviolet (UV) light liberated significantly more (.) NO than non-irradiated STZ (1134.4 +/- 104 vs. 256.9 +/- 240 nmol). Moreover, the diabetogenic effect of STZ was abolished by UV irradiation before its administration to experimental animals. In these animals the glucose and insulin values were significantly different from those of the diabetic group (151.3 +/- 16.6 vs. 364.6 +/- 63.4 mg/dl and 36.3 +/- 17.9 vs. 0.08 +/- 5.5 microIU/ml, respectively) and similar to those of the non-diabetic group (127.2 +/- 34.1 mg/dl and 41.7 +/- 13.9 microIU/ml, respectively). Carboxy-PTIO treatment returned glycemia to nearly normal levels in 60% of STZ-induced diabetic rats (157.5 +/- 11.8 vs. 364.6 +/- 63.6 mg/dl of the diabetic group). L-NAME and dexamethasone cannot return either glucose or insulin to normal levels. In conclusion, UV light increased (.) NO liberation from STZ and suppressed its diabetogenic activity. It is possible that the diabetogenic activity of STZ is related to the liberation of nitric oxide from STZ, since carboxy-PTIO scavenger had a protective effect, while L-NAME and dexamethasone did not. It is possible that an increase in (.) NO concentration into cell, independently of its endogenous or exogenous origin, can induce beta-cell damage and diabetes.

Participation of oxygen-free radicals in the oxido-reduction of proteins

Recent studies have focused attention on the possible role of active oxygen species on protein damage and degradation. The reactions of free radicals on biomolecules are important in physiology and pathology. A number of systems that generate free radicals catalyze the oxidative modification of proteins in two species: protein peroxides, which can consume important antioxidants; and proteinbound reducing moieties, which can reduce transition metals, and may enhace their activity in radical reactions. Protein oxidation also contributes to the pool of damaged enzymes and accumulation of abnormal and damaged proteins, which increases during aging and in various pathological states, such as atherosclerosis, cancer, etc

Síndrome de alcoholismo fetal. Estudio de revisión / Fetal alcohol syndrome. A review

La ingestión de etanol durante el embarazo ha sido considerada como una buen probada causa de efectos teratológicos en el embrión. El conjunto de alteraciones en el crecimiento y morfogénesis del producto son incluidas en el llamado síndrome de alcoholismo fetal (Fetal Alcohol Syndrome, FAS), caracterizado por deficiencia en el crecimiento, disfunción del SNC, anormalidades faciales y malformaciones de daño y las posibilidades de diagnóstico temprano son consideradas en la presente revisión.

Efecto citoprotector de enprostil sobre la mucosa gástrica dañada con etanol en la rata. Estudio con citoquímica de alta resolución y microscopía electrónica de barrido / Protective effect of enprostil on the cells of gastric mucosa demaged by ethanol in the rat. High resolution cytochemical scanning elelctron microscopy study

El objeto de este trabajo fue analizar la partcipación de la capa de glicoproteínas de la membrana plasmática en el efecto citoprotector de un análogo de la PGE, utilizando como modelo el estómago de la rata irritado con etanol. A un grupo de ratas Long-Evans previamente tratadas con Enprostil se les instiló 0.5 ml. de etanol absoluto por vía oral. Los animales fueron sacrificados a los 0,30 y 60 minutos y los estómagos fueron estudiados con microscopía de luz, electrónica de transmisión utilizando rojo de Rutenio como marcador y microscopía electrónica de barrido. Un grupo de ratas sólo recibió etanol. La mucosa gástrica de este último grupo reveló hiperhemia y necrosis con disociación y ausencia de la capa glicoproteica. Estos cambios no se observaron en los estómagos del grupo tratado cocn el análogo de la prostaglandina en donde estacó la capa de rojo de Rutenio. Parece ser que el efecto citoprotector de estas sustancias incluye un efecto inductor sobre la producción o secreción de glicocproteínas que se correlacionó con la microscopía electrónica de barrido