Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effect of psychological stress on lipid peroxidation activity in the mouse brain, the mechanism underlying the psychological stress-induced change in the activity, and the effects of anxiolytic and anxiogenic drugs on the activity in psychologically-stressed animals. Psychological stress exposure using a communication box paradigm for 2-16 h significantly increased the content of thiobarbituric acid reactive substance (TBARS), an index of lipid peroxidation activity, in the brain, and the effect was maximal after peaked by a 4-h stress exposure. In the animals stressed for over 4 h, the increased brain TBARS content lasted for 30 min after the stress exposure, while no significant increase of the TBARS content was observed in the liver or serum. Trolox (67.6 mg/kg, i.p.), an antioxidant drug, but not monoamine oxidase inhibitors, clorgyline (2.5-5 mg/kg, i.p.) or 5-(4-benzylphenyl)-3-(2-cyanoethyl)-(3H)-1,3,4-oxadiazol-2-o ne (1-5 mg/kg, i.p.), significantly suppressed the effect of psychological stress. The non-selective nitric oxide (NO) synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 10-100 mg/kg, i.p.) and the selective neuronal NOS inhibitor 7-nitroindazole (25 and 50 mg/kg, i.p.), but not the inducible NOS inhibitor aminoguanidine (1-100 mg/kg, i.p.), dose dependently suppressed the psychological stress-induced enhancement of lipid peroxidation in the brain. L-Arginine (300 mg/kg, i.p.), a substrate of NOS, antagonized the effect of L-NAME. Measurements of NO metabolites revealed a significant increase of NO production in the brains of stressed mice. The benzodiazepine (BZD) receptor agonist diazepam (0.05-0.5 mg/kg, i.p.), the 5-HT(1A) receptor agonists (+/-)-8-hydroxy-di-propylaminotetralin and buspirone (0.1-1 mg/kg, i. p.), but not the 5-HT(3) receptor agonist MDL72222, dose-dependently suppressed the psychological stress-induced enhancement of brain lipid peroxidation. In contrast, the administration of anxiogenic drugs, FG7142 (an inverse BZD agonist: 1-10 mg/kg, i.p.) and 1-(3-chlorophenyl)piperazine (a mixed 5-HT(2A/2B/2C) agonist: 0.1-1 mg/kg, i.p.), potentiated it. The effects of diazepam and FG7142 were abolished by the BZD receptor antagonist flumazenil (10 mg/kg, i.p.). These results indicate that psychological stress causes oxidative damage to the brain lipid via enhancing constitutive NOS-mediated production of NO, and that drugs with a BZD or 5-HT(1A) receptor agonist profile have a protective effect on oxidative brain membrane damage induced by psychological stress.
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PMID:Psychological stress-induced enhancement of brain lipid peroxidation via nitric oxide systems and its modulation by anxiolytic and anxiogenic drugs in mice. 1048 1

Psychological stress evokes a number of physiological responses, including a rise in body temperature (T(b)), which has been suggested to be the result of an elevation in the thermoregulatory set point, i.e., a fever. This response seems to share similar mechanisms with infectious fever. A growing number of studies have provided evidence that nitric oxide (NO) has a modulatory role in infectious fever, but no report exists about the participation of NO in stress fever. Thus, the present study aimed to verify the hypothesis that NO modulates stress fever by using restraint stress as a model. To this end, we tested the effects of the non-specific NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) or its inactive enantiomer N(G)-nitro-D-arginine methyl ester (D-NAME) on colonic T(b) of restrained or unrestrained rats. A rapid increase in T(b) was observed when animals were submitted to restraint. Intravenous (i.v.) injection of L-NAME at a dose (10 mg/kg) that caused no change in T(b) when administered alone significantly attenuated the elevation in T(b) elicited by stress, indicating that the NO pathway may mediate stress fever. Moreover, intracerebroventricular (i.c.v.) L-NAME (250 microg/microl) caused a rise in T(b) of euthermic animals and enhanced stress fever, supporting that NO in the central nervous system (CNS) leads to a reduction in T(b) and, therefore, this is unlikely to be the site where NO may mediate stress fever. Taken together, these data indicate that the NO pathway plays an important role in modulating restraint stress-induced fever in rats.
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PMID:The nitric oxide pathway is an important modulator of stress-induced fever in rats. 1111 Oct 4

Lactoferrin (LF) is known as an iron-binding glycoprotein. It has been shown that bovine LF (bLF) is transported into cerebrospinal fluid via blood although its physiological effects in the central nervous system (CNS) are still unclear. In this study, a suppressive effect of bLF on psychological distress was investigated in adult rats. Intraperitoneal injection of bLF (100 mg/kg) reduced stressful behaviors in a conditioned fear-induced freezing test and an elevated plus-maze test. Interestingly, the suppressive effect of bLF was enhanced by pretreatment with electric foot-shock (FS). This suppressive effect of bLF in the elevated plus-maze test was reversed by pretreatment with naloxone, an opioid receptor antagonist, at a dose of 1 mg/kg (ip). N(omega)-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase (NOS) inhibitor, also blocked the suppressive effect of bLF and foot-shock. In addition, combined application of a low dose of bLF (30 mg/kg, ip) and l-arginine (30 and 100 mg/kg, ip) showed significant potentiated effects on psychological stress. These results suggest that bLF has suppressive effects on psychological distress, especially under the condition of moderate stress. Furthermore, it is suggested that bLF possibly activates an endogenous opioidergic system via nitric oxide synthase activation.
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PMID:Suppressive effects of milk-derived lactoferrin on psychological stress in adult rats. 1553 13

Psychological stress elevates blood pressure through sympathetic nerve activation. This pressor response is supposedly associated with cardiovascular events. We investigated a sex difference in the pressor response and norepinephrine surge to cage-switch stress in rats. Wistar male and female rats were catheterized for blood pressure monitoring and blood sampling. Six days post-surgery, the rats were exposed to the cage-switch stress and blood samples were collected at rest and 30 min after the start of the stress. The stress-induced pressor response was greater in the male than in the female rats. The stress significantly increased the norepinephrine level in the male, but not in the female rats. Pre-treatment with N(G)-nitro-l-arginine methyl ester (L-NAME), a nitric oxide (NO) synthase inhibitor, attenuated the norepinephrine response significantly in the male rats. There was no sex difference in the endothelial NO synthase expression in the gastrocnemius muscle. However the phosphorylation at serine 1177, a marker for eNOS activation, was higher in the male than in the female rats. These results suggest that NO is involved in the norepinephrine surge to psychological stress in the male rats, but not in the female rats. This is the first report on a sex difference in the norepinephrine surge in response to psychological stress through NO, in association with pressor response.
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PMID:Sex difference in norepinephrine surge in response to psychological stress through nitric oxide in rats. 1717 36

Nitric oxide (NO) has been critically implicated in the central regulation of autonomic function. We recently found, however, that acute (up to 30min) blockade of NO synthase (NOS) in the rostral ventrolateral medulla (RVLM) inhibited sympathetic baroreflex transmission, without altering the cardiovascular response to psychological (air-jet) stress in rabbits. In the present study, we examined the effect of the later phase (1-3h) of NOS inhibition in the RVLM on the pressor and sympathetic responses to air-jet stress in conscious rabbits. Air-jet evoked a sustained increase in blood pressure (+14+/-2mmHg), heart rate (+37+/-9beats/min) and renal sympathetic nerve activity (+52+/-8%). Bilateral microinjection of a NOS inhibitor l-NAME (10nmol) into RVLM did not affect resting parameters or stress responses during the first 30min after injection. Conversely, in the later phase of NOS inhibition, the pressor, tachycardic and renal sympathetic responses to air-jet stress were reversibly attenuated by 48-72%. Microinjection of l-NAME outside the RVLM did not change stress responses. Microinjection of glutamate (3nmol) into the RVLM induced similar pressor effects before and after l-NAME (+30+/-6mmHg and +26+/-6mmHg, respectively). Microinjection of d-NAME altered neither stress responses nor pressor response to glutamate. These results suggest that NOS inhibition in the RVLM has a dual effect on the autonomic response to psychological stress. In the early phase, NOS inhibition has little impact on this response. However, in the later phase, NOS inhibition attenuates the stress response, perhaps via indirect mechanisms such as altering the local redox state.
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PMID:Nitric oxide synthase inhibition in rostral ventrolateral medulla attenuates pressor response to psychological stress in rabbits. 1770 84

Nuclear factor kappa B (NF-kappaB) is an important transcription factor that regulates a wide spectrum of genes including cytochrome P450 (CYP), the most important family of drug metabolizing enzymes. Therefore, in this review, we addressed the potential role of NF-kappaB in CYP regulation. We proposed three mechanisms by which NF-kappaB can regulate CYP expression and activity. First, NF-kappaB can directly regulate the expression of CYP1A1, CYP2B1/2, CYP2C11, CYP2D5, CYP2E1, CYP3A7, and CYP27B1 through binding to the promoter region of these genes. Second, NF-kappaB indirectly regulates the transcription of CYP genes through mutual repression with some nuclear receptors that are involved in CYP regulation such as AhR, CAR, GR, PXR, RXR, PPAR, FXR, and LXR. Finally, NF-kappaB can regulate CYP activity at post-transcriptional level by inducing heme oxygenase or by affecting the CYP protein stability. In addition, increased inflammatory mediators, oxidative stress, and subsequent NF-kappaB activation have been demonstrated in many conditions such as inflammatory bowel diseases, rheumatoid arthritis, psychological stress, diabetes, aging, cancer, renal diseases, and congestive heart failure. Meanwhile, there is a significant alteration of CYP expression and activity in these diseases. Therefore, we propose that NF-kappaB could be one of the links between inflammation, oxidative stress, and CYP regulation in these diseases. In conclusion, NF-kappaB plays a crucial role in the regulation of CYP through several mechanisms and this role can explain the altered CYP regulation in many conditions.
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PMID:Role of NF-kappaB in the regulation of cytochrome P450 enzymes. 1927 51

Psychological stress and glucocorticoids are associated with heightened cardiovascular disease risk. We investigated whether stress or cortisol would be associated with reduced circulating angiogenic cell (CAC) function, an index of impaired vascular repair. We hypothesized that minority-race individuals who experience threat in interracial interactions would exhibit reduced CAC function, and that this link might be explained by cortisol. To test this experimentally, we recruited 106 African American participants for a laboratory interracial interaction task, in which they received socially evaluative feedback from Caucasian confederates. On a separate day, a subset of 32 participants (mean age=26years, 47% female) enrolled in a separate biological substudy and provided blood samples for CAC isolation and salivary samples to quantify the morning peak in cortisol (the cortisol awakening response, CAR). CAC function was quantified using cell culture assays of migration to vascular endothelial growth factor (VEGF) and secretion of VEGF into the culture medium. Heightened threat in response to an interracial interaction and trait anxiety in vivo were both associated with poorer CAC migratory function in vitro. Further, threat and poorer sustained attention during the interracial interaction were associated with a higher CAR, which in turn, was related to lower CAC sensitivity to glucocorticoids. In vitro, higher doses of cortisol impaired CAC migratory function and VEGF protein secretion. The glucocorticoid receptor antagonist RU486 reversed this functional impairment. These data identify a novel, neuroendocrine pathway by which psychological stress may reduce CAC function, with potential implications for cardiovascular health.
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PMID:Circulating angiogenic cell function is inhibited by cortisol in vitro and associated with psychological stress and cortisol in vivo. 2692 33