Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0848237 (acute stress)
 4,619 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to determine the cortisol response after an immune challenge in the gilthead seabream (Sparus aurata), a cortisol receptor (GR) was cloned, sequenced and its expression determined after lipopolysaccharide (LPS) treatment. To clone the gilthead seabream GR (sbGR), consecutive PCR amplifications and screening of a pituitary cDNA library were performed. We obtained a clone of 4586 bp encoding a 784aa protein. Northern blot analysis from head kidney, heart and intestine revealed that the full length sbGR mRNA was approximately 6.5 Kb. A LPS treatment, used as an acute stress model, was employed to characterise the expression of sbGR and some selected genes involved in the immune response (IL-1beta, TNF-alpha, Mx protein, cathepsin D and PPAR-gamma). All genes were expressed in all tissues examined and responses were tissue and time dependent revealing differential gene expression profiles after LPS administration. Furthermore, analysis of plasma cortisol levels after LPS injection, showed an acute response to inflammatory stress with a significant increase two and six h after injection, recovering to basal levels 12 h post-stress in all LPS concentrations tested.
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PMID:Cloning of the glucocorticoid receptor (GR) in gilthead seabream (Sparus aurata). Differential expression of GR and immune genes in gilthead seabream after an immune challenge. 1754 9

Stress is triggered by numerous unexpected environmental, social or pathological stimuli occurring during the life of animals, including humans, which determine changes in all of their systems. Although acute stress is essential for survival, chronic, long-lasting stress can be detrimental. In this review, we present data supporting the hypothesis that stress-related events are characterized by modifications of oxidative/nitrosative pathways in the brain in response to the activation of inflammatory mediators. Recent findings indicate a key role for nitric oxide (NO) and an excess of pro-oxidants in various brain areas as responsible for both neuronal functional impairment and structural damage. Similarly, cyclooxygenase-2 (COX-2), another known source of oxidants, may account for stress-induced brain damage. Interestingly, some of the COX-2-derived mediators, such as the prostaglandin 15d-PGJ2 and its peroxisome proliferator-activated nuclear receptor PPARgamma, are activated in the brain in response to stress, constituting a possible endogenous anti-inflammatory mechanism of defense against excessive inflammation. The stress-induced activation of both biochemical pathways depends on the activation of the N-methyl-D-aspartate (NMDA) glutamate receptor and on the activation of the transcription factor nuclear factor kappa B (NFkappaB). In the case of inducible NO synthase (iNOS), release of the cytokine TNF-alpha also accounts for its expression. Different pharmacological strategies directed towards different sites in iNOS or COX-2 pathways have been shown to be neuroprotective in stress-induced brain damage: NMDA receptor blockers, inhibitors of TNF-alpha activation and release, inhibitors of NFkappaB, specific inhibitors of iNOS and COX-2 activities and PPARgamma agonists. This article reviews recent contributions to this area addressing possible new pharmacological targets for the treatment of stress-induced neuropsychiatric disorders.
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PMID:Stress-induced neuroinflammation: mechanisms and new pharmacological targets. 1914 64

Diabetes mellitus increases susceptibility to acute gastric injury and impairs ulcer healing. Pioglitazone as an agonist of peroxisome proliferator-activated receptor gamma (PPARgamma) is used as anti-diabetic drug and has additionally gastroprotective activities. However, the effect of pioglitazone on the protection and healing of gastric mucosa under diabetic conditions is poorly understood. The aim of the present study was: 1) to compare the effects of treatment with PPARg ligand (pioglitazone) on healing of acetic acid-induced gastric ulcers and prevention of acute water immersion and restraint stress (WRS)-induced gastric lesions in normal rats and those with streptozotocin (STZ)-induced diabetes mellitus; 2) to assess the effects of pioglitazone on the mRNA expression of cyclooxygenase-2 (COX-2), c-NOS, interleukin-1beta and hypoxia inducible factor-1 alpha (HIF-1alpha) in the gastric mucosa of rats with or without STZ-induced diabetes mellitus; 3) to investigate the involvement of endogenous NO and proinflammatory cytokines (IL-1beta, TNF-alpha) in healing of chronic gastric ulcers and in prevention of acute stress lesions by pioglitazone in rats with or without STZ-induced diabetes mellitus. Diabetes was induced in rats by single injection of STZ (70 mg/kg i.p.) four weeks prior to production of gastric ulcers by acetic acid method or induction of stress lesions by 3.5 hours of WRS. Non-diabetic rats were used as controls. Two major animal groups (A and B) were tested; A) diabetic and non-diabetic rats with chronic gastric ulcers treated with 1) pioglitazone (40 mg/kg-d i.g.), 2) pioglitazone in combination of blocker of NO synthase (L-NNA 20 mg/kg-d i.p.), and 3) saline (vehicle-control); and B) diabetic and non-diabetic rats exposed to 3.5 hours of WRS and pretreated with 1) pioglitazone (40 mg/kg i.g.), 2) pioglitazone in combination of blocker of NO synthase (L-NNA 20 mg/kg i.p.), and 3) saline (vehicle-control). The gastric mucosal blood flow was assessed by H(2)-gas clearance method. The area of chronic acetic acid ulcers and number of acute WRS-induced gastric lesions were assessed by planimetry or by counting of number of lesions, respectively. In rats with chronic ulcers, the mRNA expression of HIF-1alpha, IL-1beta and COX-2 was assessed by RT-PCR and protein expression of platelet endothelial cell adhesion molecule-1 (PECAM-1), COX-2 and cNOS was examined by Western blot. In rats with stress lesions, the protein expression of COX-2, cNOS, catalase, PPAR and heat shock protein 70 (HSP70) was examined by Western blot. In diabetic rats, a marked delay in ulcer healing and increased susceptibility to WRS lesions were observed and these effects were accompanied by a significant decrease in GBF. Pioglitazone significantly increased healing of chronic gastric ulcers and exerted a strong protective effect against WRS-induced lesions, but these effects were attenuated by NO-inhibition with L-NNA. Interestingly, the ulcer healing and gastroprotective effects of pioglitazone were weak under diabetic conditions, and this effect on ulcer healing was accompanied by impaired angiogenesis due to decreased PECAM-1 expression, attenuated expression of COX-2 and the increased expression of proinflammatory cytokines compared to those in diabetic rats treated with vehicle. We conclude that: 1) experimental diabetes in rats impairs healing of chronic ulcers and enhances acute stress lesions due to an increase in the expression and release of proinflammatory cytokines such as TNF-alpha and IL-1beta; 2) the ulcer healing effect of pioglitazone, which is, at least in part, mediated by endogenous NO, is significantly attenuated by L-NNA in diabetic rats despite increased COX-2 expression at the ulcer edge; 3) the formation of acute gastric lesions induced by WRS is also attenuated by pretreatment with pioglitazone due to increased GBF probably mediated by NO, as the administration of L-NNA reversed, in part, the preventive action induced by this PPARgamma ligand, and 4) pioglitazone is effective both in healing of chronic ulcers and protection against WRS lesions though its action under diabetic conditions seems to be attenuated, possibly due to reduction in NOS-NO system, angiogenesis and increased expression and release of proinflammatory cytokines.
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PMID:Gastric ulcer healing and stress-lesion preventive properties of pioglitazone are attenuated in diabetic rats. 2081 70