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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Melatonin is a hormone that is released from the pineal gland into the blood stream and is controlled by nerve impulses from the suprachiasmatic nuclei. Melatonin synthesis, which is inhibited by light on the mammalian retina, peaks in plasma concentrations during the night. Though still a subject of intense research, melatonin in mammals is known to effect the reproductive system, thyroid function, and adaptations to seasonal changes. Sled dogs in Fairbanks, Alaska (65 degrees N) can be exposed to anywhere from 21 h of daylight in the summer to 4 h in the winter. While light may be the primary factor influencing melatonin production, we hypothesized that exercise may also affect melatonin production. In the current study, sled dogs were used to study seasonal and diurnal variation in melatonin production. Sled dogs by nature are elite athletes and therefore exercise was a focus in the study. Both exercise and non exercise dogs from 2 distinct latitudes were used. The peak in melatonin production was prolonged in high latitude dogs (65 degrees N), compared with lower latitude dogs (45 degrees N). Dogs at both latitudes show a reduction in peak melatonin levels with exercise, and winter melatonin levels in both locations were higher than the summer. Surprisingly, sled dogs in Alaska had lower melatonin levels than sled dogs in New York.
Comp Biochem Physiol A Mol Integr Physiol 2007 Aug
PMID:Seasonal and diurnal melatonin production in exercising sled dogs. 1737 56

Nuclear localization of androgen receptors (ARs) is essential for their activity. Melatonin induces AR nuclear exclusion via increase in cGMP, calcium, and protein kinase C (PKC) activation, presumably through G-protein(s). The effects of regulators of G-protein signaling (RGS) on AR localization were studied in AR-expressing PC3 cells. Gi-specific RGS10 inhibited melatonin but not cGMP-induced AR nuclear exclusion, independent of androgen. No evidence for Gq activation by melatonin was found. However, Gi/Gq-selective RGS4 inhibited AR nuclear exclusion downstream of PKC activation--an effect that was abrogated by constitutively active Gq. RGS10 and RGS4, but not RGS2, ablated the inhibitory effects of melatonin on AR reporter gene activity. For the first time, these data show regulation by Gi and Gi-specific RGS protein-mediated AR nuclear exclusion, which is potentially important in the treatment of AR-dependent cancers and neurodegenerative disorders. They also reveal a role for a Gq protein downstream of PKC activation in AR nuclear localization.
J Mol Neurosci 2007
PMID:Gi and RGS proteins provide biochemical control of androgen receptor nuclear exclusion. 1741 65

Melatonin is produced in the dark by the pineal gland and is a key regulator of circadian and seasonal rhythms. A low melatonin level has been reported in individuals with autism spectrum disorders (ASD), but the underlying cause of this deficit was unknown. The ASMT gene, encoding the last enzyme of melatonin synthesis, is located on the pseudo-autosomal region 1 of the sex chromosomes, deleted in several individuals with ASD. In this study, we sequenced all ASMT exons and promoters in individuals with ASD (n=250) and compared the allelic frequencies with controls (n=255). Non-conservative variations of ASMT were identified, including a splicing mutation present in two families with ASD, but not in controls. Two polymorphisms located in the promoter (rs4446909 and rs5989681) were more frequent in ASD compared to controls (P=0.0006) and were associated with a dramatic decrease in ASMT transcripts in blood cell lines (P=2 x 10(-10)). Biochemical analyses performed on blood platelets and/or cultured cells revealed a highly significant decrease in ASMT activity (P=2 x 10(-12)) and melatonin level (P=3 x 10(-11)) in individuals with ASD. These results indicate that a low melatonin level, caused by a primary deficit in ASMT activity, is a risk factor for ASD. They also support ASMT as a susceptibility gene for ASD and highlight the crucial role of melatonin in human cognition and behavior.
Mol Psychiatry 2008 Jan
PMID:Abnormal melatonin synthesis in autism spectrum disorders. 1750 66

The decrease of melatonin production with aging contributes to the decline in immune function as organisms age. Treatment with the exogenously administered indoleamine restores the reduced immunological functions. Therefore, we investigated the effect of melatonin on viability, phagocyte ingestion capacity, and free radical generation levels of heterophils from young and old ringdove (Streptopelia risoria) aged 3-4 and 11-13 years, respectively. Animals received a single oral dose of melatonin 1 h before lights off for three consecutive days. Experiments were performed at the acrophases and nadirs of melatonin. Melatonin treatment significantly increased serum melatonin levels at the acrophases, but not at the nadirs of the two age groups. In both young and old animals there was increased heterophil viability at acrophases with respect to nadirs, and also increased cell resistance to oxidative stress in the old animals after the melatonin treatment. At acrophases, the index, percentage and efficiency of phagocytosis all increased significantly, and superoxide anion levels decreased significantly with respect to the nadir values of vehicle and melatonin-treated animals, the effect being greater in young than in old ringdoves. At the nadirs, no change was observed in any parameter analyzed. In both young and old animals, phagocytosis and melatonin were positively correlated, while superoxide anion levels and melatonin were negatively correlated. In conclusion, exogenous melatonin enhanced heterophil viability in old animals as well as increasing phagocytosis and free-radical scavenging in both age groups during the nocturnal period, accompanied by an increase in the levels of the indoleamine.
Mol Cell Biochem 2007 Oct
PMID:Effect of exogenous melatonin on viability, ingestion capacity, and free-radical scavenging in heterophils from young and old ringdoves (Streptopelia risoria). 1755 94

(1) Neurogenesis driven by neural stem cells (NSCs) is regulated by physiological and pathological factors. Melatonin (MT) has profound neurotrophic and neuroprotective effects. Hence, we studied the role of MT in regulating the viability and differentiation of NSCs derived from rat ventral midbrain. (2) NSCs were isolated from the rat ventral midbrain. The viability of NSCs was determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-ulfophenyl)-2H-tetrazolium assay. The differentiation of NSCs was examined by analyzing the expression of the neural markers, MT receptors, brain derived neurotropic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) with semi-quantitative RT-PCR, immunofluorescence cytochemistry, and Western blot. (3) Our results showed that MT could promote the viability of NSCs. In addition, MT could significantly elevate the mRNA and protein levels of tyroxine hydroxylase (TH), a marker of dopaminergic neurons, and decrease the expression of the astrocytes maker glial fibrillary acidic protein (GFAP). MT also increased the production of BDNF and GDNF in the cultured NSCs. Meanwhile, we first found that two subtypes of MT receptors, MT1 and MT2, were expressed in the ventral midbrain NSCs. (4) These results demonstrated that MT could induce NSCs to differentiate into dopaminergic neurons and decrease astrocyte production. These findings also suggest that MT could offer a beneficial tool in guiding directional differentiation of NSCs.
Cell Mol Neurobiol 2008 Jun
PMID:Melatonin regulates the viability and differentiation of rat midbrain neural stem cells. 1791 27

The chicken pineal gland possesses the capacity to generate circadian oscillations, is able to synchronize to external light:dark cycles and can generate an hormonal output--melatonin. We examined the light responses of the chicken pineal gland and its effects on melatonin and Per2, Bmal1 and E4bp4 expression in 19-day old embryos and hatchlings during the dark phase, subjective light phase and in constant darkness. Expression of Per2 and E4bp4 were rhythmic under light:dark conditions, but the rhythms of E4bp4 and Bmal1 mRNA did not persist in constant darkness in 19-day old embryos. Per2 mRNA expression persisted in constant darkness, but with a reduced amplitude. Per2 expression was inducible by light only during the subjective day. Melatonin release was inhibited by light only at end of the dark phase and during the subjective light phase in embryos. Our data demonstrate that the embryonic avian pineal pacemaker is light sensitive and can generate rhythmic output, however the effects of light were diminished in chick embryos in compared to hatchlings.
Comp Biochem Physiol A Mol Integr Physiol 2008 Jan
PMID:Ontogeny of melatonin, Per2 and E4bp4 light responsiveness in the chicken embryonic pineal gland. 1799 71

Melatonin is a biogenic amine, known from almost all phyla of living organisms. In vertebrates melatonin is produced rhythmically in the pinealocytes of the pineal gland, relaying information of the environmental light/dark cycle to the organism. With regard to crustaceans only a handful of studies exist that has attempted to identify the presence and possible daily variation of this substance. We set out to investigate whether in the crab Neohelice granulata melatonin was produced in the optic lobes of these animals and underwent rhythmic fluctuations related to the daily light/dark cycle. Our experimental animals were divided into three groups exposed to different photoperiods: normal photoperiod (12L:12D), constant dark (DD), and constant light (LL). The optic lobes were collected every 4 hours over a 24-h period for melatonin quantification by radioimmunoassay (RIA). N. granulata kept under 12 L:12D and DD conditions, showed daily melatonin variations with two peaks of abundance (p<0.05), one during the day and another, more extensive one, at night. Under LL-conditions no significant daily variations were noticeable (p>0.05). These results demonstrate the presence of a daily biphasic fall and rise of melatonin in the eyestalk of N. granulata and suggest that continuous exposure to light inhibits the production of melatonin synthesis.
Comp Biochem Physiol A Mol Integr Physiol 2008 Feb
PMID:Daily variation of melatonin content in the optic lobes of the crab Neohelice granulata. 1816 31

Previous data from our group have provided support for the role of GH, melatonin and estrogens in the prevention of aging of several physiological parameters from bone, liver metabolism, vascular activity, the central nervous system (CNS), the immune system and the skin. In the present work data on the molecular mechanisms involved are presented. A total of 140 male and female rats have been submitted to different treatments over 10 weeks, between 22 and 24 months of age. Males have been treated with GH and melatonin. Females were divided in two groups: intact and castrated at 12 months of age. The first group was treated with GH and melatonin and the second with the two latter compounds and additionally with estradiol and Phytosoya. Aging was associated with a reduction in the number of neurons of the hylus of the dentate gyrus of the hippocampus and with a reduction of neurogenesis. GH treatment increased the number of neurons but did not increase neurogenesis thus suggesting a reduction of apoptosis. This was supported by the reduction in nucleosomes and the increase in Bcl2 observed in cerebral homogenates together with an increase in sirtuin2 and a reduction of caspases 9 and 3. Melatonin, estrogen and Phytosoya treatments increased neurogenesis but did not enhance the total number of neurons. Aging induced a significant increase in mitochondrial nitric oxide in the hepatocytes, together with a reduction in the mitochondrial fraction content in cytochrome C and an increase of this compound in the cytosolic fraction. Reductions of glutathione peroxidase and glutathione S-transferase were also detected, thus indicating oxidative stress and possibly apoptosis. Treatment for 2.5 months of old rats with GH and melatonin were able to significantly and favourably affect age-induced deteriorations, thus reducing oxidative damage. Keratinocytes obtained from old rats in primary culture showed an increase in lipoperoxides, caspases 8 and 3 as well as a reduction in Bcl2 leading to enhanced number of nucleosomes that was also restored upon treatments with GH and melatonin. In conclusion, GH and melatonin treatment seem to have beneficial effects against age-induced damage in the CNS the liver and the skin through molecular mechanisms reducing oxidative stress and apoptosis.
J Steroid Biochem Mol Biol 2008 Feb
PMID:Molecular mechanisms involved in the hormonal prevention of aging in the rat. 1825 41

One of the most important functions modulated by melatonin is the synchronization of circadian rhythms. In crayfish (Procambarus clarkii), we have obtained evidence that the amplitude of the electrical response to light of the retinal photoreceptors the receptor potential, is modified by the action of melatonin and that the magnitude of this action depends on the circadian time of melatonin application. In contrast, the electroretinogram (ERG) circadian rhythm can be synchronized by either single or periodic melatonin application. In this work we hypothesized that, in crayfish, melatonin acts on effectors and on pacemaker of ERG circadian rhythm as a non-photic synchronizer. Melatonin could be a hormone that sends a signal of darkness to the ERG circadian system.
Comp Biochem Physiol A Mol Integr Physiol 2008 Apr
PMID:Melatonin modulates the ERG circadian rhythm in crayfish. 1831 59

Melatonin, the chief secretory product of the vertebrate pineal gland is suspected to be a ubiquitous molecule principally involved in the transduction of photoperiodic information. Besides vertebrates, melatonin has been detected throughout phylogeny in numerous non-vertebrate taxa. In the present study, the occurrence of melatonin in Antarctic krill Euphausia superba and its possible role in mediating seasonal metabolic changes was evaluated. Melatonin was quantified by enzyme linked immunosorbent assay (ELISA) in high performance liquid chromatography (HPLC) purified extracts of eyestalks and hemolymph of krill sampled in the Lazarev Sea during the Antarctic winter and summer. In addition, oxygen uptake rates and the activities of the metabolic enzyme malate dehydrogenase (MDH) were recorded to assess the metabolic status of krill. Validation of melatonin measurements was carried out on the basis of three different extraction methods with parallel determination of melatonin by ELISA in crude extracts and in HPLC purified extracts, and after derivatization of melatonin under alkaline conditions in the presence of hydrogen peroxide. A significantly higher respiration rate and MDH activity was found in summer krill than in winter krill indicating that krill was in a state of reduced metabolic activity during winter. However, neither during winter nor during summer there were detectable melatonin concentrations in the visual system or hemolymph of krill. Based on these results, we question a mediating role of melatonin in the control of seasonal metabolic changes in Antarctic krill.
Comp Biochem Physiol A Mol Integr Physiol 2008 Apr
PMID:Melatonin and its possible role in mediating seasonal metabolic changes of Antarctic krill, Euphausia superba. 1832 56


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