Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of l-tryptophan as precursor of serotonin and melatonin synthesis on activity-rest rhythm was studied in ring doves, Streptopelia risoria, as a representative of diurnal animals and rats, Rattus norvegicus, as a typical nocturnal one. The animals were housed in cages equipped for horizontal activity recording in a thermostatized chamber and submitted to a 12/12h light/dark photoperiod (lights on at 08:00 h). After acclimatization, the animals received vehicle (methylcellulose) and l-tryptophan (240 mg/kg) by esophagic cannula 2h before the onset of either light or dark phase. Also, oral melatonin (2.5mg/kg) was tested for comparative purposes. After nocturnal l-tryptophan administration, rats showed increased activity (149%), while the opposite occurred in ring doves (39% decrease). No significant changes were found after diurnal l-tryptophan intake in either species. Melatonin produced effects similar to those of l-tryptophan. These results suggest that the effects of l-tryptophan administration are dependent on the nocturnal/diurnal habits of the studied species and, most probably, are mediated by increased melatonin synthesis.
Comp Biochem Physiol A Mol Integr Physiol 2006 Jun
PMID:Opposite effects of tryptophan intake on motor activity in ring doves (diurnal) and rats (nocturnal). 1662 87

Melatonin effects are discussed by reviewing results from mice with intact or disrupted melatonin signaling. Melatonin, the neuroendocrine hand of the clock produced in the pineal gland during night, acts upon two receptor subtypes. Melatonin receptors are found in the suprachiasmatic nuclei (SCN), hypophysial pars tuberalis (PT) and adrenal gland. In SCN, melatonin interacts with PACAP, a neuropeptide of the retinohypothalamic tract. Moreover, melatonin acts on the SCN to modulate the activity of the sympathetic nervous system. Melatonin is not required to maintain rhythmic clock gene expression in SCN. By contrast, the rhythmic clock gene expression in PT depends on a melatonin signal interacting with adenosine. Melatonin may also affect clock gene protein levels in the adrenal cortex and influence adrenal functions. In conclusion, melatonin may serve the synchronization of peripheral oscillators by interacting with other neuroactive substances. A stress-reducing potency of melatonin needs to be explored in further studies.
Mol Cell Endocrinol 2006 Jun 27
PMID:Mice, melatonin and the circadian system. 1664 97

Anthracycline antibiotics, such as doxorubicin and daunorubicin, constitute a group of wide spectrum therapeutic agents. Application of these drugs in chemotherapy is limited because of their toxic effects. Melatonin, the main secretory product of pineal gland, was recently found as a free radical scavenger and antioxidant. We decided to evaluate the tissue protective effect of melatonin against toxic effects of doxorubicin in six groups of rats. Rats were given doxorubicin (Dx) (45 mg/kg dose), melatonin (MEL) (10 mg/kg), first doxorubicin and then melatonin (DM), first melatonin and then doxorubicin (MD). The degree of kidney, lung, liver and brain cells' alterations were examined biochemically. In doxorubicin-treated group, malondialdehyde (MDA) levels of kidney, lung, liver and brain tissues were significantly increased but glutathione (GSH) levels were decreased compared to control rats. In the group in which first doxorubicin and then melatonin were given, MDA levels were significantly decreased compared to the doxorubicin-treated group. In doxorubicin-treated group, serum levels of creatinine, uric acid, blood urea nitrogen (BUN), Gamma-glutamyl transpeptidase (GGT) and Lactic acid dehydrogenase (LDH) were significantly increased while serum albumin and total protein levels were significantly decreased compared to control rats. Melatonin decreased the intensity of the changes produced by the administration of doxorubicin alone. Melatonin was quite efficient in reducing the formation of lipid peroxidation, restoring the tissue GSH contents and alterations of serum levels.
Mol Cell Biochem 2006 Jun
PMID:Effects of melatonin in reducing the toxic effects of doxorubicin. 1665 24

Melatonin induces nuclear exclusion of the androgen receptor (AR) via activation of protein kinase C (PKC). The specific members of the PKC superfamily involved in AR nuclear exclusion were investigated in prostate cancer PC3 cells stably transfected with the wild-type androgen receptor (PC3-AR). PKCalpha was essentially cytoplasmic whereas PKCbeta and PKCepsilon were essentially membranal, suggesting their constitutive activity in the PC3-AR cells. Melatonin treatment induced membrane association of PKCalpha in a time and dose dependent manner. The PKCalpha and PKCbeta1 specific inhibitor GO6976 and the PKCbeta isoform-specific inhibitor hispidin had no effects on AR localization under basal conditions. However, GO6976 but not hispidin negated the melatonin-mediated nuclear exclusion of the AR. These data indicate that PKCalpha activation is a critical step in AR nuclear exclusion by melatonin. They also imply that PKCalpha-activation is a potentially effective way to control of the AR activity in prostate cancer cells.
Mol Cell Endocrinol 2006 Jun 27
PMID:Role of protein kinase Calpha in melatonin signal transduction. 1669 22

1. Glial cells are the most abundant cell population in the central nervous system. The aim of this study was to examine the effects of melatonin, 7-nitroindazole, and riluzole on glutamate toxicity in primary glial cell culture. 2. Glutamate toxicity was induced by addition of 100 microM glutamate to the cultures, and then 100 microM melatonin, 500 microM 7-nitroindazole, and 10 (M riluzole were administered in different groups. Lactate Dehydrogenase activity and nitrite levels were determined at the 1st, 6th, and 24th h. 3. Melatonin, 7-nitroindazole, and riluzole decrease Lactate Dehydrogenase activity at the 1st, 6th, and 24th h (at all hours, p<0.05). Nitrite levels were decreased by melatonin and riluzole at the 1st, 6th, and 24th h. 4. In this study, we observed that melatonin, 7-nitroindazole, and riluzole are effective as protective agents on glutamate toxicity in mixed glial cells.
Cell Mol Neurobiol 2007 Mar
PMID:Neuroprotective agents: is effective on toxicity in glial cells? 1675 18

Melatonin and its major metabolite, 6-sulphatoxymelatonin, can routinely be measured by RIA or ELISA. Plasma, serum or saliva samples maybe used for melatonin measurement and urine for the metabolite. Melatonin is a hormone produced by the pineal gland witha clear circadian rhythm giving low levels by day and a peak during the night in normally entrained individuals. The timing of sample collection for measurement is therefore crucial. Melatonin levels are primarily assessed to determine the timing of an individual's internal body clock and therefore indicate any misalignment to the 24 h day.
Methods Mol Biol 2006
PMID:Measurement of melatonin and 6-sulphatoxymelatonin. 1676 82

We hypothesized that intense exercise training (forced swimming for 30 min, 5 days/week) may enhance the progression of mammary carcinogenesis through the involvement of stress hormones, such as catecholamines and prolactin, which can promote breast cancer. After the appearance of the DMBA-induced tumors in Sprague-Dawley rats, the effect was evaluated of exercise-induced stress (with or without administration of the hormone melatonin) on the survival time, tumor multiplicity, and tumor growth until the death of the animals. In a second set of experiments, after one month of exercise, the NK cells count in blood, and the plasma concentrations of catecholamines and prolactin were determined. Although no significant change was found in either the survival time of the rats or the tumor multiplicity, exercise significantly increased the tumor growth rate. Stress was confirmed by the enhanced adrenaline and prolactin concentrations in the blood of the exercised rats. Exercise-induced stress did not change the percentage of NK cells in the tumor-bearing rats. Melatonin counteracted the increased tumor growth, returning the prolactin and adrenaline concentrations to their optimal physiological levels in the exercised tumor-bearing rats, thus confirming an "anti-stress" role of this hormone. In conclusion, intense exercise-induced stress enhances mammary carcinogenesis through the involvement of adrenaline and prolactin. The results also confirmed a role of melatonin as a therapeutic aid against breast cancer in general, and in particular during situations of stress.
Mol Cell Biochem 2007 Jan
PMID:Exercise-induced stress enhances mammary tumor growth in rats: beneficial effect of the hormone melatonin. 1713 43

A beta vaccination as a therapeutic intervention of Alzheimer's has many challenges, key among them is the regulation of inflammatory processes concomitant with excessive generation of free radicals seen during such interventions. Here we report the beneficial effects of melatonin on inflammation associated with A beta vaccination in the central and peripheral nervous system of mice. Mice were divided into three groups (n=8 in each): control, inflammation (IA), and melatonin-treated (IAM). The brain, liver, and spleen samples were collected after 5 days for quantitative assessment of plasma lipid peroxides (LPO), an oxidative stress marker, and antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (Gpx). IA group mice have shown the elevated concentration of LPO significantly while there was a reduction at antioxidant enzyme levels. In addition, a significant (P<0.05) reduction in neurotransmitters like dopamine (DA), 5-hydroxytryptamine (5-HT), and norepinephrine (NE) was also observed in the IA group mice. Nevertheless, their metabolites, such as homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA) increased significantly (P<0.05) as compared to control. Samples were further evaluated at microscopic level to examine the neuropathological changes by immunohistochemical methods. Melatonin treatment effectively reversed these above changes and normalized the LPO and antioxidant enzyme levels (P<0.05). Furthermore, melatonin salvaged the brain cells from inflammation. Our Immunohistochemical findings in the samples of melatonin-treated animals (IAM group) indicated diminished expression of glial fibrillary acidic protein (GFAP) and nuclear factor kappa B (Nf kappa B) than those observed in the IA group samples. Our results suggest that administration of melatonin protects inflammation associated with A beta vaccination, through its direct and indirect actions and it can be an effective adjuvant in the development of vaccination in immunotherapy for Alzheimer's disease (AD).
Mol Cell Biochem 2007 Apr
PMID:Anti-inflammatory effect of melatonin on A beta vaccination in mice. 1713 82

Melatonin is an indoleamine widely distributed in the evolution that shows a great functional versatility, playing an important role as a transmitter of photoperiodic information and exhibiting antioxidant, oncostatic, anti-aging and immunomodulatory properties. In vertebrates, this molecule is produced by the pineal gland and other extrapineal sites. The present study was carried out to investigate the presence of melatonin in thymus and the possibility of an endogenous melatonin synthesis in this organ, in which T cells are matured. In this work, we demonstrate in humans and rats that thymus contains melatonin, expresses the mRNAs encoding N-acetyltransferase and hydroxyindol-O-methyltransferase, the two key enzymes of the melatonin synthesis, and has this biosynthetic machinery activated. In addition, rat thymocytes cultured for 24 h exhibited high levels of melatonin. The results presented here suggest that human and rat thymuses are able to synthesize melatonin, which could have intracrine, autocrine and paracrine functions.
Cell Mol Life Sci 2007 Mar
PMID:Melatonin biosynthesis in the thymus of humans and rats. 1733 63

Sleep is a neurochemical process involving sleep promoting and arousal centers in the brain. Sleep performs an essential restorative function and facilitates memory consolidation in humans. The remarkably standardized bouts of consolidated sleep at night and daytime wakefulness reflect an interaction between the homeostatic sleep need that is manifested by increase in sleep propensity after sleep deprivation and decrease during sleep and the circadian pacemaker. Melatonin, the hormone produced nocturnally by the pineal gland, serves as a time cue and sleep-anticipating signal. A close interaction exists between the sleep-wake, melatonin, core temperature, blood pressure, immune and hormonal rhythms leading to optimization of the internal temporal order. With age the robustness of the circadian system decreases and the prevalence of sleep disorders, particularly insomnia, increases. Deviant sleep patterns are associated with increased risks of morbidity, poor quality of life and mortality. Current sleep pharmacotherapies treat insufficient sleep quantity, but fail to improve daytime functioning. New treatment modalities for sleep disorders that will also improve daytime functioning remain a scientific and medical challenge.
Cell Mol Life Sci 2007 May
PMID:Sleep and sleep disturbances: biological basis and clinical implications. 1736 43


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