Abstract：
:Abnormal proliferation and motility of retinal pigment epithelial cells leads to proliferative vitreoretinopathy (PVR). Melatonin is a known effective antitumour and anti-invasive agent, but whether it affects the formation and underlying mechanisms of PVR remains unclear. In this study, the results of the MTT assay, colony formation and propidium iodide (PI) staining with flow cytometry revealed that melatonin dose dependently inhibited epidermal growth factor (EGF)-induced proliferation of human ARPE-19 cells. Furthermore, melatonin reduced EGF-induced motility by suppressing cathepsin S (CTSS) expression. Pretreatment with ZFL (a CTSS inhibitor) or overexpression of CTSS (pCMV-CTSS) significantly inhibited EGF-induced cell motility when combined with melatonin. Epidermal growth factor induced the phosphorylation of AKT(S473)/mTOR (S2448) and transcription factor (c-Jun/Sp1) signaling pathways. Pretreatment of LY294002 (a PI3K inhibitor) or rapamycin (an mTOR inhibitor) markedly reduced EGF-induced motility and p-AKT/p-mTOR/c-Jun/Sp1 expression when combined with melatonin. Taken together, these data indicate that melatonin inhibited EGF-induced proliferation and motility of human ARPE-19 cells by activating the AKT/mTOR pathway, which is dependent on CTSS modulation of c-Jun/Sp1 signalling. Melatonin may be a promising therapeutic drug against PVR.
journal_name
J Pineal Resjournal_title
Journal of pineal researchauthors
Yang SF,Chen YS,Chien HW,Wang K,Lin CL,Chiou HL,Lee CY,Chen PN,Hsieh YHdoi
10.1111/jpi.12615subject
Has Abstractpub_date
2020-01-01 00:00:00pages
e12615issue
1eissn
0742-3098issn
1600-079Xjournal_volume
68pub_type
杂志文章abstract：:The age-related changes and the acute effects of intravenous melatonin on the activity of striatal neurons of 1-, 3-, 6-, 12-, and 18-month-old sham-operated and pinealectomized rats were investigated. There was a decline in responsiveness from 3- to 18-months of age, although in sham-pinealectomized rats the response...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1995.tb00174.x
更新日期：1995-09-01 00:00:00
abstract：:In the current study, a fundamental question, that is, the mechanisms related to the beneficial effects of melatonin on mammalian embryonic development, was addressed. To examine the potential beneficial effects of melatonin on bovine embryonic development, different concentrations of melatonin (10(-11), 10(-9), 10(-7...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12126
更新日期：2014-04-01 00:00:00
abstract：:A physiologically based model of arousal dynamics is improved to incorporate the effects of the light spectrum on circadian phase resetting, melatonin suppression, and subjective sleepiness. To account for these nonvisual effects of light, melanopic irradiance replaces photopic illuminance that was used previously in ...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12681
更新日期：2020-10-01 00:00:00
abstract：:Melatonin influences plant innate immunity through the mitogen-activated protein kinase (MAPK) pathway. However, the most upstream MAPK component in melatonin signaling and the dependence of generation of a reactive oxygen species (ROS) burst on melatonin synthesis and signaling remain unclear. In this study, treatmen...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12379
更新日期：2017-03-01 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 produced following circadian rhythm with high levels being released at night and has been implicated in the regulation of physiological processes in major tissues, including the pancreas. The aim of our study was to examine the effects of melatonin on intracellular free Ca(2+) concentration ([Ca(2+) ](c))...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2010.00790.x
更新日期：2010-10-01 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：:An interaction between melatonin and adrenocorticotropin (ACTH) seems to occur in humans and both hormones respond to beta-adrenergic stimulation. As in lower animal species, human pineal gland also contains alpha2-adrenergic receptors as does the hypothalamus-pituitary axis. In this study the response of the pineal g...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1034/j.1600-079x.2000.290107.x
更新日期：2000-08-01 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：:The frequency of mitoses of adrenaline (A) cells and noradrenaline (N) cells in the adrenal medulla of nonoperated (NO), sham-operated (SPX), and pinealectomized (PX) male, 53-day-old Holtzman rats (n = 133) was investigated by means of light microscopy. Animals were killed at eight time points during a standardized 2...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1990.tb00803.x
更新日期：1990-01-01 00:00:00
abstract：:Melatonin secretion is an endogenous synchronizer, and it may possess some anti-aging properties. Thus we examined melatonin levels in physiological aging, in extreme senescence and in senile dementia. In healthy old (age 66-94 yr) and young subjects (age 23-39 yr) and in demented patients (age 68-91 yr) plasma melato...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2004.00125.x
更新日期：2004-05-01 00:00:00
abstract：:In previous studies, we have shown that mitochondrial respiratory chain (MRC) activity is decreased in patients with nonalcoholic steatohepatitis and in ob/ob mice and that peroxynitrite plays a pathogenic role. The present study examined whether melatonin, a peroxynitrite scavenger, prevents: (i) the in vitro effects...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2011.00868.x
更新日期：2011-08-01 00:00:00
abstract：:This study examined plasma melatonin levels and the suppressant effect of light on melatonin production in the squirrel monkey. Monkeys were maintained on a 12:12 light-dark cycle (LD 12:12) with lights on from 07:00 to 19:00. Plasma levels of melatonin were determined by gas chromatography negative chemical ionizatio...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1990.tb00689.x
更新日期：1990-01-01 00:00:00
abstract：:The presence of melatonin and the enzymes (transcripts and activities) involved in its synthesis, i.e. arylalkylamine N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT), was investigated in the eggs and early embryos of Japanese quail at Hamburger-Hamilton stages 1-10. Melatonin was present in ...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2007.00421.x
更新日期：2007-04-01 00:00:00
abstract：:Melatonin (MT), endogenously secreted by the pineal gland, is closely related to multiple biological processes; however, its effect on thrombopoiesis is still not well illustrated. Here, we demonstrate that MT administration can elevate peripheral platelet levels. Analysis of different stages in thrombopoiesis reveals...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12637
更新日期：2020-04-01 00:00:00
abstract：:Production of melatonin in the pineal gland of inbred mice such as C57B1/6J, BALB/c and AKR strains is still a matter of debate. In previous studies, we and other authors showed that these strains of inbred mice have a clear-cut circadian rhythm of serum melatonin and urinary 6-hydroxy-melatonin-sulphate. In contrast,...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1996.tb00249.x
更新日期：1996-04-01 00:00:00
abstract：:Incorporation of new therapeutic agents remains as a major challenge for treatment of patients with malignant haematological disorders. Melatonin is an indolamine without relevant side effects. It has been shown previously to exhibit synergism with several chemotherapeutic drugs in Ewing sarcoma cells by potentiating ...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2010.00850.x
更新日期：2011-04-01 00:00:00
abstract：:Our objective was to suppress the daily surge of melatonin in serum of prepubertal dairy heifers by manipulating intensity of light (Experiment 1) and duration of exposure to light (Experiment 2). Heifers in Experiment 1 were exposed to either 12 hr of darkness (000 lux, control), or 400, 800, or 1,200 lux of light du...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1992.tb00046.x
更新日期：1992-05-01 00:00:00
abstract：:Five adult pasture-bred Prim Holstein cows were used to document the time invariance of melatonin disposition in the cow. Melatonin was administered by an intravenous route as a bolus (5 micrograms/kg of body weight) at either 1430 or 2230. Data were analysed according to a three-compartment open model with melatonin ...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1993.tb00521.x
更新日期：1993-10-01 00:00:00
abstract：:We evaluated the antioxidant property of melatonin as it relates to the vasospastic effect of hydrogen peroxide (H2O2) on the human umbilical artery. Helical sections of umbilical arteries were obtained from healthy pregnant women who were delivered between weeks 37 and 39 of gestation. Changes in maximal potassium ch...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1997.tb00318.x
更新日期：1997-04-01 00:00:00
abstract：:In healthy young men, administration of a single light pulse (5000 lux for 3 hr) or a single melatonin pill (5 mg) at 20:40 hr under controlled constant routine conditions of <10 lux, yielded a phase delay and a phase advance, respectively, in the circadian marker of dim light melatonin onset 24 hr later. Phase shifts...
journal_title：Journal of pineal research
pub_type： 临床试验,杂志文章
doi：10.1111/j.1600-079x.2004.00117.x
更新日期：2004-04-01 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：:Melatonin possesses a number of important biologic activities including oncostatic, anti-oxidant, and immunostimulatory actions. This study was designed to assess the effects of melatonin on inflammation-related gene expression in lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMCs), us...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2007.00452.x
更新日期：2007-09-01 00:00:00
abstract：:Day and nighttime melatonin production in the pineal gland was compared in normal and cardiomyopathic (polydystrophic) adult male Syrian hamsters. These strains of hamsters were selected for comparison because the cardiomyopathetic hamster displays a deficient transmembrane Ca(2+)-pump in a number of tissues, and intr...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1991.tb00472.x
更新日期：1991-10-01 00:00:00
abstract：:Melatonin is known to regulate a variety of physiological processes including control of circadian rhythms, regulation of seasonal reproductive function, regulation of body temperature, and so forth. Accumulating evidence from in vitro and in vivo experiments using rodent and chicken has also suggested that melatonin ...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2006.00410.x
更新日期：2007-04-01 00:00:00
abstract：:No previous reports have described the effects of an increase in endogenous melatonin levels on plant yield and reproduction. Here, the phenotypes of melatonin-rich transgenic rice plants overexpressing sheep serotonin N-acetyltransferase were investigated under field conditions. Early seedling growth of melatonin-ric...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12129
更新日期：2014-05-01 00:00:00
abstract：:Ischemia/reperfusion injury (IRI) is harmful to the cardiovascular system and causes mitochondrial oxidative stress. Numerous data indicate that the JAK2/STAT3 signaling pathway is specifically involved in preventing myocardial IRI. Melatonin has potent activity against IRI and may regulate JAK2/STAT3 signaling. This ...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12070
更新日期：2013-10-01 00:00:00
abstract：:Melatonin and its precursor, l-tryptophan, have been shown to exert gastroprotective effects in animals, but their influence on the gastric damage by aspirin (ASA) in humans has been sparingly investigated. In this study, we designed to determine the effects of melatonin and l-tryptophan on ASA-induced gastric mucosal...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.2010.00755.x
更新日期：2010-05-01 00:00:00
abstract：:Both autophagy and melatonin play important roles in plant development and stress response. However, the direct correlation between autophagy and melatonin as well as the underlying mechanism remains elusive in plants. In this study, we discovered that the expression of three autophagy-associated genes (MeATG8b, 8c, a...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12652
更新日期：2020-08-01 00:00:00
abstract：:Glaucoma may be associated with circadian disruption due to its association with a loss of intrinsically photosensitive retinal ganglion cells. Clinical evidence demonstrating an association between glaucoma and circadian disruption is limited, and no large-scale studies have been performed. The purpose of this cross-...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12662
更新日期：2020-09-01 00:00:00
