Lipidomics Provides New Insight into Pathogenesis and Therapeutic Targets of the Ischemia-Reperfusion Injury

Lipids play an essential role in both tissue protection and damage. Tissue ischemia creates anaerobic conditions in which enzyme inactivation occurs, and reperfusion can initiate oxidative stress that leads to harmful changes in membrane lipids, the formation of aldehydes, and chain damage until cell death. The critical event in such a series of harmful events in the cell is the unwanted accumulation of fatty acids that leads to lipotoxicity. Lipid analysis provides additional insight into the pathogenesis of ischemia/reperfusion (I/R) disorders and reveals new targets for drug action. The profile of changes in the composition of fatty acids in the cell, as well as the time course of these changes, indicate both the mechanism of damage and new therapeutic possibilities. A therapeutic approach to reperfusion lipotoxicity involves attenuation of fatty acids overload, i.e., their transport to adipose tissue and/or inhibition of the adverse effects of fatty acids on cell damage and death. The latter option involves using PPAR agonists and drugs that modulate the transport of fatty acids via carnitine into the interior of the mitochondria or the redirection of long-chain fatty acids to peroxisomes

Single and Combined Effects of Acute and Chronic Non-Thermal Stressors on Rat Interscapular Brown Adipose Tissue Metabolic Activity

The aim of this study was to examine whether the thermogenic potential of rat interscapular brown adipose tissue (IBAT) changes in response to acute and/or chronic exposure to non-thermal stressors (immobilization and isolation), by measuring the uncoupling protein 1 (UCP-1) content, MAO-A, SOD and CAT activities, as well as the number of IBAT sympathetic noradrenaline-containing nerve fibers. Both acute immobilization (2 h) and chronic isolation (21 days), as well as their combined effects, significantly increased the IBAT UCP-1 content in comparison to non-stressed animals. When applied individually, stressors increased the number of sympathetic fibers in comparison to controls, whereas in combination they decreased it. The activity of IBAT monoamine oxidase-A (MAO-A) decreased under the influence of each stressor independent of its type or duration. SOD activity coincided with MAO-A decrement, whereas CAT activity had an opposite pattern of changes. We conclude that acute and chronic exposure to non-thermal stressors, immobilization and isolation, respectively, affect the metabolic potential of rat IBAT, judging by the increase in UCP-1 content and sympathetic outflow. However, when acute immobilization was applied as a novel stressor to previously chronically isolated animals, an increase in the UCP-1 content was accompanied by a lower IBAT sympathetic outflow, suggesting that IBAT metabolic function under various stress condition is not solely dependent on SNS activity

Peripheral oxytocin treatment affects the rat adreno-medullary catecholamine content modulating expression of vesicular monoamine transporter 2

The neuropeptide oxytocin has been shown to influence on neuroendocrine function. The aim of the present study was to investigate the effect of peripheral oxytocin treatment on the synthesis, uptake and content of adreno-medullary catecholamine. For this purpose oxytocin (3.6 mu g/100 g body weight, s.c) was administrated to male rats once a day over 14 days. In order to assess the effect of peripheral oxytocin treatment on adreno-medullary catecholamine we measured epinephrine and norepinephrine content and gene expression of tyrosine hydroxylase (TH), norepinephrine transporter (NET) and vesicular monoamine transporter 2 (VMAT2) in the adrenal medulla. Our results show a significant increase of epinephrine (1.7-fold, p LT 0.05) and norepinephrine (1.5-fold, p LT 0.05) content in oxytocin treated animals compared to saline treated ones. Oxytocin treatment had no effect either on mRNA or protein level of TH and NET. Under oxytocin treatment the increase in VMAT2 mRNA level was not statistically significant, but it caused a significant increase in protein level of VMAT2 (3.7-fold, p LT 0.001). These findings indicate that oxytocin treatment increases catecholamine content in the rat adrenal medulla modulating VMAT2 expression. (C) 2013 Elsevier Inc. All rights reserved

Novel acute stressor effects on interscapular brown adipose tissue sympathetic inervation and UCP-1 content in chronically isolated and spontaneously hypertensive rats

Interscapular brown adipose tissue (IBAT) is an energy storing organ involved in the maintenance of homeostasis in stress conditions when the balance of energy supplies is disturbed. The major regulator of IBAT activity is the sympathetic nervous system (SNS). Since genetic background is responsible for the individual differences in neuroendocrine stress responsivity, spontaneously hypertensive rats (SHR) that have a genetically increased general sympathetic output are a useful model for studying adaptive processes in stress conditions. Our aim was to test the effect of acute and/or chronic exposure to various stressors (thermal-cold, psychophysical-immobilization and psychosocial-isolation) on IBAT SNS and the metabolic activity in SHR, by measuring the number of monoamine-containing nerve endings and uncoupling protein-1 (UCP-1) content. The obtained results show that the IBAT SNS activity of unstressed SHR was stimulated by the administration of a single acute or chronic stressor and was independent of the duration or type of stressor, while chronic pre-stress of isolation suppressed further the SNS reaction to novel acute stress exposure. The IBAT UCP-1 content followed SNS changes, suggesting that this system is dominant in the regulation of IBAT metabolic rate in SHR

Distinct and combined effects of acute immobilization and chronic isolation stress on MAO activity and antioxidative protection in the heart of normotensive and spontaneously hypertensive rats

The heart is an organ especially sensitive to the sympathetic overstimulation and therefore to the influence of stressors and hypertension. The aim of the present study was to investigate the effect of two distinct types of stressors, acute immobilization (2 h) and chronic isolation stress (21 days), as well as their combined effect on the activity of monoamine oxidase (MAO), superoxide dismutase, catalase (CAT) and the ascorbic acid (AA) content in the heart of normotensive and spontaneously hypertensive rats (SHR). The results obtained show that in basal conditions heart MAO and CAT activity (p LT 0.05), as well as AA concentration (p LT 0.01) were higher in SHR than in normotensive ones. The acute immobilization significantly decreased heart MAO activity in both examined strains (p LT 0.01). On the other hand, chronic isolation, separately or in combination with immobilization, did not affect this enzyme, in the heart of either hypertensive or normotensive rats, which was associated with the reduced antioxidative protection (p LT 0.01, p LT 0.05)

Specific regulation of ACTH secretion under the influence of low and high ambient temperature-The role of catecholamines and vasopressin

The response of hypothalamo-pituitary-adrenocortical (HPA) axis to different stressors depends on numerous stimulatory and inhibitory signals gathering from various parts of the brain to the hypothalamic nuclei. The present study was aimed at determining whether catecholamines (CA) and vasopressin (VP) play the role in the specific regulation of adrenocorticotropic hormone (ACTH) secretion under the influence of thermal stressors, cold (+4 degrees C) and heat (+38 degrees C), applied acutely for 1 h or repeatedly during 7 and 14 day (1 h daily). The results showed that following acute exposure to those stressors, hypothalamic dopamine (DA), noradrenaline (NA) and adrenaline (ADR) concentrations were significantly decreased as compared to non stressed controls. The prolonged exposure to either of the two stressors left hypothalamic CA concentration unaffected. The amount of pituitary VP significantly increased only under the influence of acute heat stress. Prolonged exposure to both stressors induced significant decrease in the pituitary VP content. Unlike the heat, the cold-caused changes in circulating VP did not follow those in the pituitary. The applied stressors significantly increased the amount of the pituitary V1b receptor (V1bR) mainly present at the surface of corticotrophs, depending on both duration of exposure and nature of stressor. Additionally, both cold and heat specifically induced an increase in blood ACTH. In conclusion, this studys results suggest that the role of VP in the regulation of the ACTH secretion in response to cold and heat depends on the type of stressor, whereas the role of the CA depends on the manner of exposure. (C) 2012 Elsevier Ltd. All rights reserved