Abstract:
:Melatonin has shown particular promise as a neuroprotective agent to prevent motoneuron death in animal models of both amyotrophic lateral sclerosis (ALS) and spinal cord injuries (SCI). However, an understanding of the roles of endogenous melatonin receptors including MT1, MT2, and orphan G-protein receptor 50 (GPR50) in neuroprotection is lacking. To address this deficiency, we utilized plasmids for transfection and overexpression of individual melatonin receptors in the ventral spinal cord 4.1 (VSC4.1) motoneuron cell line. Receptor-mediated cytoprotection following exposure to glutamate at a toxic level (25 μm) was determined by assessing cell viability, apoptosis, and intracellular free Ca(2+) levels. Our findings indicate a novel role for MT1 and MT2 for increasing expression of the calcium-binding proteins calbindin D28K and parvalbumin. Increased levels of calbindin D28K and parvalbumin in VSC4.1 cells overexpressing MT1 and MT2 were associated with cytoprotective effects including inhibition of proapoptotic signaling, downregulation of inflammatory factors, and expression of prosurvival markers. Interestingly, the neuroprotective effects conferred by overexpression of MT1 and/or MT2 were also associated with increases in the estrogen receptor β (ERβ): estrogen receptor α (ERα) ratio and upregulation of angiogenic factors. GPR50 did not exhibit cytoprotective effects. To further confirm the involvement of the melatonin receptors, we silenced both MT1 and MT2 in VSC4.1 cells using RNA interference technology. Knockdown of MT1 and MT2 led to an increase in glutamate toxicity, which was only partially reversed by melatonin treatment. Taken together, our findings suggest that the neuroprotection against glutamate toxicity exhibited by melatonin may depend on MT1 and MT2 but not GPR50.
journal_name
J Pineal Resjournal_title
Journal of pineal researchauthors
Das A,Wallace G 4th,Reiter RJ,Varma AK,Ray SK,Banik NLdoi
10.1111/j.1600-079X.2012.01022.xsubject
Has Abstractpub_date
2013-01-01 00:00:00pages
58-68issue
1eissn
0742-3098issn
1600-079Xjournal_volume
54pub_type
杂志文章abstract::The effects of noradrenergic and cholinergic receptor agonists on intracellular Ca2+ concentration ([Ca2+]i) in single dissociated rat pineal cells were investigated by microfluorimetric measurements in Fura-2 acetoxymethyl ester (Fura-2/AM) loaded cells. Noradrenaline (NA) evoked characteristic biphasic increments of...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079x.1996.tb00266.x
更新日期:1996-08-01 00:00:00
abstract::The oncostatic effects of melatonin on the mammary gland have been studied in transgenic mice carrying the N-ras proto-oncogene under the control of the MMTV-LTR. Female (4-week-old) virgin mice with positive transgenic pedigrees were injected with melatonin (200 micrograms/mouse/ day, five times a week) or vehicle la...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079x.1997.tb00308.x
更新日期:1997-03-01 00:00:00
abstract::Preterm delivery is the leading cause of neonatal mortality and contributes to delayed physical and cognitive development in children. At present, there is no efficient therapy to prevent preterm labor. A large body of evidence suggests that intra-amniotic infections may be a significant and potentially preventable ca...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/jpi.12108
更新日期:2014-03-01 00:00:00
abstract::A role of D2-dopaminergic neurotransmission in the regulation of melatonin biosynthesis in retina was studied in vivo in chickens. The nighttime rise in serotonin N-acetyltransferase (NAT)--the penultimate and key regulatory melatonin-synthesizing enzyme--was potently inhibited by both acute light exposure and agonist...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079x.1991.tb00466.x
更新日期:1991-10-01 00:00:00
abstract::We have studied the postnatal evolution of the glial cells in the rat pineal gland after its chemical pre- and perinatal denervation, by the assessment of the immunocytochemical expression of three antigens characteristic of glial cells i.e., vimentin (VIM), glial fibrillary acidic protein (GFAP), and S-100 protein. T...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079x.1995.tb00160.x
更新日期:1995-05-01 00:00:00
abstract::In mammals, the suprachiasmatic nuclei (SCN) constitute the main circadian clock, receiving input from the retina which allows synchronization of endogenous biological rhythms with the daily light/dark cycle. Over the year, the SCN encodes photoperiodic variations through duration of melatonin secretion, with abundant...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/jpi.12711
更新日期:2020-12-16 00:00:00
abstract::Melatonin binding sites were characterized in rat spleen crude membranes. The specific binding of 2-[125I]iodomelatonin by spleen crude membranes fulfills all the criteria for binding to a receptor site. Thus, binding was dependent on time and temperature, stable, specific, and increased under constant light exposure ...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079x.1996.tb00236.x
更新日期:1996-01-01 00:00:00
abstract::The purpose of this study was to determine and compare the light sensitivity of two commercially important, phylogenetically different teleost species in terms of melatonin production. Three series of experiments were performed on both Atlantic salmon and European sea bass. First, a range of light intensities were tes...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079X.2006.00330.x
更新日期:2006-08-01 00:00:00
abstract::Melatonin is an indoleamine synthesized in the pineal gland, and after its release into the blood, it has an extensive repertoire of biological activities, including antitumoral properties. In this study, we found that melatonin reduced the growth of the human melanoma cells SK-MEL-1. The antiproliferative effect was ...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079X.2010.00765.x
更新日期:2010-08-01 00:00:00
abstract::Obesity, a major risk factor for ischemic heart disease, is associated with increased oxidative stress and reduced antioxidant status. Melatonin, a potent free radical scavenger and antioxidant, has powerful cardioprotective effects in lean animals but its efficacy in obesity is unknown. We investigated the effects of...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079X.2010.00826.x
更新日期:2011-03-01 00:00:00
abstract::Recent investigations have demonstrated that melatonin influences carbohydrate metabolism mediated by insulin-inhibiting effects on pancreatic β-cells. This study evaluated whether melatonin has also an effect on pancreatic α-cells and glucagon expression as well as the glucagon secretion in vitro and in vivo. Glucago...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079X.2010.00848.x
更新日期:2011-04-01 00:00:00
abstract::Melatonin is a powerful scavenger of oxygen free radicals. In humans, melatonin is rapidly transferred from the maternal to the fetal circulation. To investigate whether or not maternal melatonin administration can protect the fetal rat brain from radical-induced damage by increasing the activities of antioxidant enzy...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1034/j.1600-079x.2001.280204.x
更新日期:2000-03-01 00:00:00
abstract::Melatonin, the main secretory product of the pineal gland, has been shown to be potentially effective in prevention of numerous types of neurodegenerative disorders in which free radical processes are involved. Homocysteine (Hcy), an independent risk factor for atherosclerosis, undergoes auto-oxidation and generates r...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1034/j.1600-079x.2003.02939.x
更新日期:2003-01-01 00:00:00
abstract::Aging induces changes in several organs and tissues, such as the liver, and this process might be due to oxidative damage caused by free radicals and inflammatory mediators. Melatonin is a secretory product with well-known antioxidant properties. The aim of this study was to investigate the effect of melatonin adminis...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079X.2004.00199.x
更新日期:2005-05-01 00:00:00
abstract::The aim of this study was to determine, in the rat, the interaction between melatonin and cholecystokinin in the regulation of the ileal interdigestive motility. This was analyzed by the chronic electromyography technique. Ileal motility was defined by the presence of intermittent spike bursts corresponding to the con...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079x.1994.tb00117.x
更新日期:1994-09-01 00:00:00
abstract::In this study, the effect of melatonin on sodium arsenite (arsenite)-induced peripheral neurotoxicity was investigated using dorsal root ganglion (DRG) explants. After 24-hr incubation, arsenite (30 microm) consistently elevated the expression of heat shock protein 70 and haeme oxygenase-1, two well-known stress prote...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079X.2008.00629.x
更新日期:2009-01-01 00:00:00
abstract::Excessive production of nitric oxide (NO) may play a detrimental role in the process of hypoxia-related neuropathology. This study explored whether treatment with melatonin would attenuate the neuropathological changes in the vagal ganglia following a severe hypoxic insult. Thirty minutes prior to hypoxia treatment, y...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1034/j.1600-079x.2002.1816.x
更新日期:2002-03-01 00:00:00
abstract::UV radiation (UVR) induces serious structural and functional alterations in human skin leading to skin aging and carcinogenesis. Reactive oxygen species are key players in UVR-mediated photodamage and induce the DNA-base-oxidized, intermediate 8-hydroxy-2'-deoxyguanosine (8-OHdG). Herein, we report the protective acti...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/jpi.12018
更新日期:2013-04-01 00:00:00
abstract::In desert areas, mammals such as camel and goat are exposed to harsh environmental conditions. The ambient temperature (Ta) cycles have been shown to entrain the circadian clock in the camel. In the present work, we assumed that, in the goat living in a desert biotope, Ta cycles would have the same synchronizing effec...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/jpi.12634
更新日期:2020-04-01 00:00:00
abstract::Antioxidant activity of a molecule is attributed to various mechanisms such as prevention of chain initiation, binding of transition metal ion catalysts and decomposition of peroxides. This study was aimed at evaluating the metal chelating and hydrogen peroxide (H2O2) scavenging activity of melatonin. The metal chelat...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1034/j.1600-079x.2003.00042.x
更新日期:2003-05-01 00:00:00
abstract::Oxidative stress is involved in ischemia-reperfusion injury and allograft rejection after transplantation. We studied two well-known antioxidants, melatonin and ascorbic acid (AA), in relation to the survival of a pancreas transplantation model without immunosuppression. Forty-eight Landrace pigs were divided into thr...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079X.2011.00908.x
更新日期:2011-11-01 00:00:00
abstract::A major goal of plant biotechnology is to improve the nutritional qualities of crop plants through metabolic engineering. Melatonin is a well-known bioactive molecule with an array of health-promoting properties, including potent antioxidant capability. To generate melatonin-rich rice plants, we first independently ov...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/jpi.12120
更新日期:2014-04-01 00:00:00
abstract::Melatonin is an excellent free radical scavenger, reacting with tert-butoxyl and cumyloxyl radicals with rate constants of 3.4 x 10(7) and 6.7 x 10(7) M-1s-1, respectively. Reaction with benzophenone triplet occurs with a near-diffusion-controlled rate constant of 7.6 x 10(9) M-1s-1 in acetonitrile and probably involv...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079x.1995.tb00188.x
更新日期:1995-11-01 00:00:00
abstract::Bisphenol A (BPA) has been reported to adversely affect the mammalian reproductive system in both sexes. However, the underlying mechanisms regarding how BPA disrupts the mammalian oocyte quality and how to prevent it have not been fully defined. Here, we document that BPA weakens oocyte quality by impairing both oocy...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/jpi.12396
更新日期:2017-04-01 00:00:00
abstract::The role played by postsynaptic alpha-adrenergic receptors in the stimulation of pineal melatonin production was investigated in the Syrian hamster. The studies were conducted using organ cultured pineal glands collected from both anatomically intact and superior cervical ganglionectomized hamsters. Results obtained i...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079x.1989.tb00437.x
更新日期:1989-01-01 00:00:00
abstract::Recent studies implicate melatonin in the antinociceptive activity of sensory neurons. However, the underlying mechanisms are still largely unknown. Here, we identify a critical role of melatonin in functionally regulating Cav3.2 T-type Ca2+ channels (T-type channel) in trigeminal ganglion (TG) neurons. Melatonin inhi...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/jpi.12476
更新日期:2018-05-01 00:00:00
abstract::The Syrian hamster pineal displays age-dependent changes in melatonin output measured in vitro. Between the ages of 4 and 19 days, pineal melatonin generation in response to 10 microM norepinephrine (NE) increased 34-fold. Production of melatonin by cultured pineals from 1-week-old hamsters showed a clear dose respons...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079x.1991.tb00475.x
更新日期:1991-10-01 00:00:00
abstract::The effect of light on melatonin biosynthesis was examined in detached rice (Oryza sativa cv. Asahi) leaves during the senescence process. The detached leaves were exposed to senescence treatment either in constant darkness or in constant light, and subjected to HPLC analysis for melatonin and its precursors. Higher m...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079X.2012.00976.x
更新日期:2012-08-01 00:00:00
abstract::The binding characteristics of the tritiated pineal hormone, [3H] melatonin, were studied in brain tissues using in vitro binding techniques. In synaptosomal membranes prepared from rat hippocampus and subjected to preincubation at 37 degrees C and multiple washings, high-affinity binding of [3H] melatonin significant...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079x.1987.tb00844.x
更新日期:1987-01-01 00:00:00
abstract::Studies on farm animals have contributed significantly to our increased understanding of basic melatonin-related physiological mechanisms, as well as to the regulation of reproduction and pelage in individual domestic species. This review concentrates on recent work on the role of melatonin in the regulation of porcin...
journal_title:Journal of pineal research
pub_type: 杂志文章,评审
doi:10.1111/j.1600-079x.1994.tb00097.x
更新日期:1994-05-01 00:00:00