Low-dose ionizing irradiation affects ntpdase activity in neuoronal cells of young female rats

In the present study, time-dependent effects of low-dose ionizing irradiation on membrane-bound enzyme activity in neuronal cell endings of young female rat brains were sudied. The ecto-adenosine triphospho diphosphohydrolases (NTPDases) hydrolyse the extracellular nucleotide di- and tri- phosphates (ADP and ATP) in the presence of divalent cations (Ca2+ and Mg2+). The influence of whole-body irradiation on membrane enzymes ATP and ADP hydrolysing activity were monitored 1, 24 and 72 h after irradiation. Animals were divided into three groups: non-treated, under physiological conditions (C), immobilized and whole body irradiated with 50 cGy by γ-rays (R) and immobilized non-irradiated (I) animals. It was shown that the levels of ATP and ADP hydrolyses were not affected within 72h after immobilisation. Lowdose irradiation significantly decreased hydrolyses of extracellular ATP as early as 1h after irradiation. ADP hydrolyses within 72 h and ATP hydrolysis after 24 h were not altered.Physical chemistry 2006 : 8th international conference on fundamental and applied aspects of physical chemistry; Belgrade (Serbia); 26-29 September 200

Low dose gamma-irradiation alters the expression of p53 protein in the rat hippocampus

The tumor-suppressor p53 protein and glucocorticoid receptor (GR) respond to different types of stress. In an attempt to reveal the possibility that p53 protein is involved in the regulation of GR gene expression after low dose cranial irradiation (CI) with 2 Gy, we examined the expression of p53 mRNA and protein as well as expression of GR mRNA and protein in the hippocampus of 18-days-old rats. We found that p53 mRNA expression was unchanged after CI, while induction of p53 protein was rapid, leading to the accumulation of p53 protein in the cytoplasm. Irradiation leads to stimulated GR gene expression in a time-dependent manner, whereas the level of GR protein was unchanged after CI. Co-immunoprecipitation has not showed that wild type p53 protein physically interacts with the GR in the cytoplasm. Our data suggest that the low dose cranial irradiation leads to stabilization of the 53 protein, without interaction with GR protein the cytoplasm.Physical chemistry 2006 : 8th international conference on fundamental and applied aspects of physical chemistry; Belgrade (Serbia); 26-29 September 200

Different induction of dual corticosteroid receptor system in the rat hippocampus following gamma radiation

Cranial radiotherapy (CRT) is an effective way to prevent CNS relapse in children with acute lymphoblastic leukemia (ALL). However, CRT also has serious side effects on normal tissues, including long-term neuroendocrine disturbances. In order to test this clinical protocol on animals, we examined the effects of CRT (10 Gy) on the level of mRNA for glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) in the hippocampus of 8-days-old rats. Irradiation rapidly stimulated GR gene expression in a time-dependent manner, whereas the time-course of MR mRNA expression showed no statistically significant changes. At postnatal day 42, the level of GR mRNA was diminished while the level of MR mRNA remained unchanged compared to matched controls. Dexamethasone suppression test (DST) revealed the altered nucleocytoplasmic shuttling of activated GR after CRT in 42-days-old rats, as a long-term consequence of gamma irradiation.Physical chemistry 2006 : 8th international conference on fundamental and applied aspects of physical chemistry; Belgrade (Serbia); 26-29 September 200

Errata Corrige: Stress-Induced Phosphorylation of C-Jun-N-Terminal Kinases and Nuclear Translocation of Hsp70 in the Wistar Rat Hippocampus (Vol 61, Pg 1, 2009)

In the paper entitled: Adžić, M., Đorđević, A., Krstić-Demonacos, M., & Radojčić, M. B. (2009). Stress-induced phosphorylation of c-Jun-N-terminal kinases and nuclear translocation of Hsp70 in the Wistar rat hippocampus. Archives of Biological Sciences, 61(1), 1-8. Fig. 1, on page 4, section b, should read "Nucleus" instead of "Cytoplasm

Chronic psychosocial isolation alters hsp70/gr and hsp90/gr ratios in response to novel acute stress in rat hypothalamus

It is known that chronic psychosocial isolation (CPSI) exerts maladaptive effect on the hypothalamic-pituitary-adrenal (HPA) axis activity. Since the hypothalamus (HT) is a major driver of the HPA axis activity and since glucocorticoid receptor protein (GR) mediates HPA axis negative feedback particularly in this structure, we studied the effect of CPSI by following the expression of GR and its chaperones hsp70 and hsp90 in HT. Our results showed that the ratios of HSPs/GR set by the CPSI were altered in response to a novel acute stress, which indicated negative CPSI influence on GR functions in HT

Fluoxetine decreases the level of nuclear glucocorticoid receptor in wistar rat hippocampus under chronic stress

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathophysiology of depression and stress disorders. Glucocorticoids, key regulators of stress response, have diverse effects on cellular processes in the hippocampus. Beside non genomic pathways, glucocorticoids effects are mediated through activation of the glucocorticoid receptor (GR), a ligand activated transcriptional factor that belongs to the nuclear hormone receptor superfamily. We analysed the GR protein level both, in the cytoplasmic and nuclear compartments in Wistar rat hippocampus, exposed to 3 week social isolation stress upon chronic fluoxetine treatment. Under chronic stress, corticosterone level was decreased compared to the control and treatment with fluoxetine did not change its level significantly in stressed animals. At the molecular level, fluoxetine significantly decreased the level of nuclear GR protein in the brain hippocampus of the chronically stressed rats. Fluoxetine reversed the nuclear level of GR disrupted by chronic psychosocial isolation (CPSI), but it failed to normalize HPA axis activity

Effects of ghrelin on protein expression of antioxidative enzymes and iNOS in the rat liver

Introduction: We investigated the effects of ghrelin on protein expression of the liver antioxidant enzymes superoxide dismutases (SODs), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR), nuclear factor kappa B (NF kappa B) and inducible nitric oxide synthase (iNOS). Furthermore, we aimed to investigate whether extracellular regulated protein kinase (ERK1/2) and protein kinase B (Akt) are involved in ghrelin-regulated liver antioxidant enzymes and iNOS protein expression. Material and methods: Male Wistar rats were treated with ghrelin (0.3 nmol/5 mu l) injected into the lateral cerebral ventricle every 24 h for 5 days, and 2 h after the last treatment the animals were sacrificed and the liver excised. The Western blot method was used to determine expression of antioxidant enzymes, iNOS, phosphorylation of Akt, ERK1/2 and nuclear factor kappa B (NF kappa B) subunits 50 and 65. Results: There was significantly higher protein expression of CuZnSOD (p LT 0.001), MnSOD (p LT 0.001), CAT (p LT 0.001), GPx, (p LT 0.001), and GR (p LT 0.01) in the liver isolated from ghrelin-treated animals compared with control animals. In contrast, ghrelin significantly (p LT 0.01) reduced protein expression of iNOS. In addition, phosphorylation of NF kappa B subunits p65 and p50 was significantly (p LT 0.001 for p65; p LT 0.05 for p50) reduced by ghrelin when compared with controls. Phosphorylation of ERK1/2 and of Akt was significantly higher in ghrelin-treated than in control animals (p LT 0.05 for ERK1/2; p LT 0.01 for Akt). Conclusions: The results show that activation of Akt and ERK1/2 is involved in ghrelin-mediated regulation of protein expression of antioxidant enzymes and iNOS in the rat liver

Stress-Induced Phosphorylation of C-Jun-N-Terminal Kinases and Nuclear Translocation of Hsp70 in the Wistar Rat Hippocampus

Glucocorticoids are key regulators of the neuroendocrine stress response in the hippocampus. Their action is partly mediated through the subfamily of MAPKs termed c-jun-N-terminal kinases (JNKs), whose activation correlates with neurodegeneration. The stress response also involves activation of cell protective mechanisms through various heat shock proteins (HSPs) that mediate neuroprotection. We followed both JNKs and Hsp70 signals in the cytoplasmic and nuclear compartments of the hippocampus of Wistar male rats exposed to acute, chronic, and combined stress. The activity of JNK1 was decreased in both compartments by all three types of stress, while the activity of cytoplasmic JNK2/3 was elevated in acute and unaltered or lowered in chronic and combined stress. Under all stress conditions, Hsp70 translocation to the nucleus was markedly increased. The results suggest that neurodegenerative signaling of JNKs may be counteracted by increase of nuclear Hsp70, especially under chronic stress

Fluoxetine decreases glutathione reductase in erythrocytes of chronically isolated wistar rats

Alterations in the antioxidative defense parameters upon chronic stress are considered critical for pathophysiology of stress related psychiatric disorders and their status in blood serves as biomarker for effects of pharmacological treatments. We investigated the modulation of erythrocyte antioxidant enzymes (AOEs): superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GLR) protein expression and activity in Wistar male rats subjected to chronic psychosocial isolation and/or treated with fluoxetine. Chronically isolated animals exhibited decreased levels of plasma corticoserone (CORT). AOEs status was not altered either by chronic social isolation or by fluoxetine. The only exception was GLR, whose level and activity were both markedly reduced by fluoxetine. Our study indicates that fluoxetine treatment of chronically isolated male Wistar rats, leads to significant reduction in the level and activity of GLR in the erythrocytes

The Effects ofAronia melanocarpaJuice Consumption on the mRNA Expression Profile in Peripheral Blood Mononuclear Cells in Subjects at Cardiovascular Risk

Foods and food products that contain polyphenols are proposed to modulate risk of cardiovascular disease. The aim of this three-arm, crossover, randomized, double-blind, placebo-controlled intervention study was to examine the impact ofAronia melanocarpajuice (AMJ), high-polyphenol (AMJ treatment, 1.17 g/100 mL polyphenols) and low-polyphenol (dAMJ treatment, 0.29 g/100 mL polyphenols) dose, on the transcriptome in peripheral blood mononuclear cells (PBMC) of 19 subjects at cardiovascular risk. Transcriptome data were obtained by microarray. Bioinformatic functional annotation analysis was performed on both the whole transcriptome datasets and the differentially expressed genes (DEGs). Expression of selected DEGs was validated by RT-qPCR. Administration of AMJ and dAMJ treatments during the two consecutive four-week treatment periods had additive effects on PBMC transcriptome profiles, with the most pronounced and specific effect noticed for AMJ in the last treatment period (TP3) of the trial. Between the high-dose and low-dose treatments in TP3, there was a multitude of overlapping DEGs and DEG-enriched biological processes and pathways, which primarily included immunomodulation and regulation of cell proliferation/death. Increased expression ofTNF,IL1B,IL8,RGS1,OSM, andDUSP2in TP3 was confirmed by RT-qPCR. The results suggest the immunomodulatory effects of prolonged habitual consumption of polyphenol-rich aronia juice in individuals at cardiovascular risk