Abstract：
:Melatonin regulates mitogen-activated protein kinase (MAPK) and Akt signaling pathways. The MAPK family mainly includes extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK). Our previous study documented that melatonin delays osteoblast proliferation; however, the mechanism of action of melatonin remains unclear. Here, we demonstrate that melatonin significantly inhibited phosphorylation of ERK but not p38, JNK, or Akt in a human osteoblastic cell line 1.19 (hFOB), as measured by western blot. The expression of ERK, p38, JNK, and Akt was not altered. PD98059 (a selective inhibitor of MEK that disrupts downstream activation of ERK) and melatonin alone, and especially in combination, significantly induced an antiproliferative effect, G(1) and G(2) /M phase arrest of the cell cycle, and downregulation of the expression at both the protein and mRNA levels of cyclin D1 and CDK4, related to the G(1) phase, and of cyclin B1 and CDK1, related to the G(2) /M phase, as measured by the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) method, flow cytometry after propidium iodide staining, and both western blot and real-time PCR, respectively. Moreover, the combination of PD98059 and melatonin synergistically and markedly augmented the action of either agent alone. Coimmunoprecipitation further confirmed that there was an interaction between phosphorylation of ERK and cyclin D1, CDK4, cyclin B1, or CDK1, which was weaken in the presence of melatonin or PD98059. These results suggest that the prevention of ERK activation is involved in melatonin-induced G(1) and G(2) /M phase arrest, and this inhibitory effect is potentially via the ERK, but not p38, JNK, or Akt, pathway.
journal_name
J Pineal Resjournal_title
Journal of pineal researchauthors
Liu L,Zhu Y,Xu Y,Reiter RJdoi
10.1111/j.1600-079X.2011.00971.xsubject
Has Abstractpub_date
2012-08-01 00:00:00pages
60-6issue
1eissn
0742-3098issn
1600-079Xjournal_volume
53pub_type
杂志文章abstract：:A decrease in nocturnal serum melatonin levels was reported in patients with clinically uncharacterized coronary artery disease. To assess whether there was a correlation between melatonin production and disease stage, we measured the nocturnal urinary excretion of 6-sulphatoxymelatonin (an index of blood melatonin co...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1034/j.1600-079x.2000.290302.x
更新日期：2000-10-01 00:00:00
abstract：:The activity of N-acetyltransferase (NAT) and the content of melatonin (MEL) in the rat pineal have been shown to be sensitive to several types of stressors. This study was designed to assess the role of the adrenals in mediating the effect of one such stressor, insulin-induced hypoglycemia, on pineal synthetic activi...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1987.tb00879.x
更新日期：1987-01-01 00:00:00
abstract：:The purpose of this study was to determine whether melatonin treatment would mitigate retinal ganglion cell (RGC) death in the developing retina following a hypoxic insult. Lipid peroxidation (LPO), glutathione (GSH), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) concentrations, expression of vascular end...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12016
更新日期：2013-03-01 00:00:00
abstract：:This study examined the factors that may be involved in altering the function of pineal gland in hypoxic conditions. Adult Wistar rats were subjected to hypoxia and the pineal gland was examined for the mRNA and protein expression of hypoxia-inducible factor-1alpha (HIF-1alpha), vascular endothelial growth factor (VEG...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2007.00424.x
更新日期：2007-04-01 00:00:00
abstract：:Urotoxicity is one of the major problems associated with cyclophosphamide (CP) chemotherapy in cancer patients. Melatonin is a potent antioxidant and reduces CP-induced urotoxicity. However, the molecular mechanisms of protection offered by melatonin are not yet clear. The present study investigated the role of nuclea...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2010.00756.x
更新日期：2010-05-01 00:00:00
abstract：:Melatonin injected in a single intraperitoneal dose of 100 micrograms/100 g b.w. to euhydrated rats resulted in a decrease of neurohypophysial oxytocin content but the hypothalamic oxytocin storage as well as the hypothalamo-neurohypophysial storage of vasopressin were not changed. Following 8 d of once-daily melatoni...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1986.tb00743.x
更新日期：1986-01-01 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：:The effect of melatonin on thrombin-induced [3H]-arachidonic acid (AA) metabolism to cyclooxygenase derivatives was determined in platelets obtained from normal volunteers at 0830 and 2030 h. Percent conversion of radioactive AA was generally greater at 2030 h than at 0830 h for every cyclooxygenase derivative analyze...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1991.tb00465.x
更新日期：1991-10-01 00:00:00
abstract：:5-Methoxycarbonylamino-N-acetyltryptamine (MCA-NAT) has been initially described as a ligand at non MT(1), non MT(2) melatonin binding site (MT3) selective versus MT(1) and MT(2), two membrane melatonin receptors. MCA-NAT activity has been reported by others in different models, in vivo, particularly in the intra-ocul...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2010.00746.x
更新日期：2010-04-01 00:00:00
abstract：:The serum levels of the pineal hormone melatonin were determined by radioimmunoassay (RIA) in 4-h intervals throughout a 24-h period in elderly men with different types of prostate tumors: benign prostatic hyperplasia (BPH, n = 13), incidental carcinoma (PCi, n = 5), and nonmetastasizing carcinoma (PC, n = 9), as well...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1985.tb00633.x
更新日期：1985-01-01 00:00:00
abstract：:Melatonin was tested in an ongoing attempt to find the endogenous antagonists of quinolinic acid, an endogenous convulsant. Among a great number of metabolites that have been tried before, only a few were found (cerulein and quinaldic acid in mice and kynurenic acid in rats). In SHR (bred from Swiss) male mice, intrac...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1998.tb00535.x
更新日期：1998-05-01 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：:A review of the literature indicates that the absolute oral bioavailability of exogenous melatonin in humans or in preclinical animal models has not been adequately characterized; hence, this study was undertaken. Pharmacokinetics of melatonin was studied in rats, dogs, and monkeys following intravenous and oral admin...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1997.tb00302.x
更新日期：1997-01-01 00:00:00
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...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2012.01022.x
更新日期：2013-01-01 00:00:00
abstract：:Maternal hyperthermia induces early embryonic death via increased oxidative stress to the embryo. In this study, we examined whether melatonin administered to heat-stressed pregnant mice would reduce hyperthermia-induced embryonic death. Mice were heat stressed (12 hr at 35 degrees C, 60% relative humidity) on the day...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2005.00260.x
更新日期：2005-10-01 00:00:00
abstract：:Environmental pollution in the form of particulate matter <2.5 μm (PM2.5 ) is a major risk factor for diseases such as lung cancer, chronic respiratory infections, and major cardiovascular diseases. Our goal was to show that PM2.5 eliciting a proinflammatory response activates the immune-pineal axis, reducing the pine...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12636
更新日期：2020-04-01 00:00:00
abstract：:Oxidative stress is reported as one of the most widely accepted mechanisms of maneb (MB)- and paraquat (PQ)-induced nigrostriatal dopaminergic neurodegeneration leading to the Parkinson's disease (PD) phenotype. The study investigated the effects of silymarin, an antioxidant of plant origin, and melatonin, an indoleam...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2010.00819.x
更新日期：2011-03-01 00:00:00
abstract：:Previous human studies have indicated that daytime melatonin levels increase when the organism is subjected to the stress of fasting and exercise. Melatonin, epinephrine, and norepinephrine levels were measured during a mock run and in the course of treadmill exercise performed before (T-1), during (T-2), and followin...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1989.tb00666.x
更新日期：1989-01-01 00:00:00
abstract：:Melatonin, a potent antioxidant, has shown to be beneficial in murine Venezuelan equine encephalomyelitis (VEE) virus infection. In addition, melatonin can induces the production of interleukin-1 beta (IL-1beta), a cytokine capable of inducing increased expression of inducible nitric oxide synthase; the activity of th...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2006.00381.x
更新日期：2007-03-01 00:00:00
abstract：:Melatonin and somatostatin are known to exert similar effects on locomotor activity. We have previously demonstrated that acute melatonin treatment regulates somatostatin receptor function in the rat frontoparietal cortex. However, the effects of subchronic and chronic melatonin treatment on the somatostatin receptor-...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1034/j.1600-079x.2002.02906.x
更新日期：2002-11-01 00:00:00
abstract：:Impaired Ca2+ homeostasis and smooth muscle contractility co-exist in acute cholecystitis (AC) leading to gallbladder dysfunction. There is no pharmacological treatment for this pathological condition. Our aim was to evaluate the effects of melatonin treatment on Ca2+ signaling pathways and contractility altered by ch...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2007.00520.x
更新日期：2008-04-01 00:00:00
abstract：:The circadian clock plays a vital role in physiology and behavior such as the sleep-wake cycle and blood pressure and hormone levels. Immune responses also display circadian rhythmicity and particularly pineal melatonin contributes to immunological processes. Little attention, however, is given to mechanisms underlyin...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12230
更新日期：2015-05-01 00:00:00
abstract：:Light and electron microscopic demonstrations for acid phosphatase (AcPase) activity in the chicken pineal gland were studied with special reference to the changes induced by the light-dark cycle. AcPase-positive lysosomes and Golgi cisternae and vesicles located in the pinealocyte in the light period are well develop...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1989.tb00407.x
更新日期：1989-01-01 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：:Melatonin is found in a wide variety of plant species. Several investigators have studied the physiological roles of melatonin in plants. However, its role is not well understood because of the limited information on its biosynthetic pathway. To clarify melatonin biosynthesis in plants, we isolated a cDNA-coded arylal...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2009.00673.x
更新日期：2009-05-01 00:00:00
abstract：:Melatonin has been shown to improve in vitro fertilization and offspring survival after bacterial infection, but its role in regulating maternal-fetal communication during early pregnancy has not been investigated. Results of this study demonstrated expression of abundant melatonin receptors in conceptus and endometri...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12670
更新日期：2020-09-01 00:00:00
abstract：:Elevated levels of soluble cellular adhesion molecules have been reported in patients with acute coronary syndromes. Likewise, a relation between decreased nocturnal melatonin levels and coronary artery disease has been suggested. The aim of the present study was to investigate the day-night variations in the concentr...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2007.00529.x
更新日期：2008-01-01 00:00:00
abstract：:Cell movement is generated by a driving force provided by dynamic cytoskeletal organization. Two main cytoskeletal-dependent features, essential for migration, are the highly cell polarized structure and focal adhesion complexes. Cell migration and substrate anchorage are finely regulated by external signaling exerted...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2008.00600.x
更新日期：2009-01-01 00:00:00
abstract：:A link between endotoxemia and nonalcoholic fatty liver disease (NAFLD) has been demonstrated in human and rodent animals. Nevertheless, the molecular mechanisms of endotoxin-evoked NAFLD remain poorly understood. We hypothesize that reactive oxygen species (ROS) mediate lipopolysaccharide (LPS)-evoked hepatic lipid a...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2011.00905.x
更新日期：2011-11-01 00:00:00
abstract：:We have studied the effect of the administration of two doses of melatonin (melatonin 100 and melatonin 200 microg/kg bw) on diabetes and oxidative stress experimentally induced by the injection of streptozotocin (STZ) in female Wistar rats. STZ was injected as a single dose (60 mg/kg i.p. in buffered citrate solution...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1998.tb00545.x
更新日期：1998-09-01 00:00:00
