Abstract:
:Melatonin protects cells against various types of oxidative stress-induced apoptosis due primarily to its ability to effectively scavenge pathological and disease condition-augmented generation of mitochondrial reactive oxygen species (mROS). Once produced, mROS indiscriminately damage mitochondrial components and more importantly they crucially activate directly the mitochondrial permeability transition (MPT), one of the critical mechanisms for initiating post mitochondrial apoptotic signaling. Whether or not melatonin targets directly the MPT, however, remains inconclusive, particularly during oxidative stress. This study, thus, investigated this possibility of an 'oxidation free Ca(2+) stress' in the presence of vitamin E after ionomycin exposure as a sole Ca(2+)-mediated MPT in order to exclude melatonin's primary antioxidative effects as well as Ca(2+)-mediated oxidative stress. The studies were carried out using cultured rat brain astrocytes RBA-1. With the application of laser scanning multiple fluorescence imaging microscopy, we visualized for the first time multiple mitochondrial protective effects provided by melatonin during Ca(2+) stress. First, melatonin, due to its primary antioxidative actions, completely prevented mCa(2+)-induced mROS formation during ionomycin exposure. Secondly, when melatonin(')s antioxidative effects were prevented due to the addition of vitamin E, melatonin significantly prevented mCa(2+)-mediated MPT and apoptosis suggesting its direct targeting of the MPT. Surprisingly, in the presence of cyclosporin A, a MPT inhibitor, melatonin reduced further mCa(2+)-mediated apoptosis during ionomycin exposure also suggesting its targeting beyond the MPT. As astrocytes are actively involve in regulating synaptic transmission and neurovascular coupling in the CNS, these multiple mitochondrial layers of protection provided by melatonin against mCa(2+)-and/or mROS-mediated apoptosis in astrocytes may be crucial for future therapeutic prevention and treatment of astrocyte-mediated neurodegenerative diseases in the CNS.
journal_name
J Pineal Resjournal_title
Journal of pineal researchauthors
Jou MJ,Peng TI,Hsu LF,Jou SB,Reiter RJ,Yang CM,Chiao CC,Lin YF,Chen CCdoi
10.1111/j.1600-079X.2009.00721.xsubject
Has Abstractpub_date
2010-01-01 00:00:00pages
20-38issue
1eissn
0742-3098issn
1600-079Xpii
JPI721journal_volume
48pub_type
杂志文章abstract::Entraining effect of melatonin on the circadian rhythm in rat pineal N-acetyltransferase (NAT) activity was studied under various photoperiods. Melatonin administration prior to dark onset for 5 successive days phase-advanced the evening NAT rise under the light:dark (LD) cycle of either LD 10:14 or LD 8:16, but not u...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079x.1992.tb00070.x
更新日期:1992-11-01 00:00:00
abstract::While ectopic overexpression of serotonin N-acetyltransferase (SNAT) in plants has been accomplished using animal SNAT genes, ectopic overexpression of plant SNAT genes in plants has not been investigated. Because the plant SNAT protein differs from that of animals in its subcellular localization and enzyme kinetics, ...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/jpi.12392
更新日期:2017-04-01 00:00:00
abstract::Optic atrophy 1 (OPA1)-related mitochondrial fusion and mitophagy are vital to sustain mitochondrial homeostasis under stress conditions. However, no study has confirmed whether OPA1-related mitochondrial fusion/mitophagy is activated by melatonin and, consequently, attenuates cardiomyocyte death and mitochondrial str...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/jpi.12542
更新日期:2019-03-01 00:00:00
abstract::N-acetylserotonin methyltransferase (ASMT) is the final enzyme in a biosynthetic pathway that produces melatonin. ASMT may play a rate-limiting role in the production of this bioactive molecule in plants. There are three ASMT genes (ASMT1-ASMT3) in the rice genome, but only ASMT1 has been functionally characterized. A...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/jpi.12088
更新日期:2013-11-01 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::The aim of this study was to compare the circadian control of melatonin production in teleosts. To do so, the effects of ophthalmectomy on circulating melatonin rhythms were studied along with ex vivo pineal culture in six different teleosts. Results strongly suggested that the circadian control of melatonin productio...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079X.2007.00480.x
更新日期:2007-11-01 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::The milk-ejecting response of lactating mouse mammary gland tissue to ovine pineal extracts indicated the presence of a neurohormone-like bioactivity in this tissue. After successive fractionation on gel permeation chromatography and reversed-phase liquid chromatography (HPLC) in conjunction with radioimmunoassays (RI...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079x.1988.tb00800.x
更新日期:1988-01-01 00:00:00
abstract::Melatonin displays antioxidant and free radical scavenger properties. Due to its ability with which it enters cells, these protective effects are manifested in all subcellular compartments. Recent studies suggest a role for melatonin in mitochondrial metabolism. To study the effects of melatonin on this organelle we u...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1034/j.1600-079x.2000.280407.x
更新日期:2000-05-01 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 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::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::This study aimed to elucidate whether melatonin would exert beneficial effects on the neuronal functions of the nodose ganglion (NG) following acute hypoxic insult. The cytochrome oxidase (COX) and the nicotinamine adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry along with the nitric oxide synthase ...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079X.2005.00238.x
更新日期:2005-09-01 00:00:00
abstract::The purpose of this study was to determine and compare the effects of chronic melatonin treatment in vivo on several aspects of prolactin (PRL) cell activity (PRL synthesis, storage, and release) in vitro in male and female Syrian hamsters. Adult male and female hamsters were maintained on long photoperiod and treated...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079x.1989.tb00446.x
更新日期:1989-01-01 00:00:00
abstract::Melatonin, a major pineal secretory product, exerts a range of physiological and neuroprotective effects. However, the functional significance of melatonin in determining neural identity, and the mechanisms by which this may occur, is unknown. In this study, P19 cells were used as a model system and cell behavior was ...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/jpi.12153
更新日期:2014-09-01 00:00:00
abstract::Glioblastoma stem-like cells (GSCs) displaying self-renewing and tumor-propagating capacity play a particularly important role in maintaining tumor growth, therapeutic resistance, and tumor recurrence. Therefore, new therapeutic strategies focusing on impairing GSC maintenance are urgently needed. Here, we used GSCs i...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/jpi.12341
更新日期:2016-09-01 00:00:00
abstract::Experiments were designed to test the hypothesis that the pineal gland mediates the effects of changing day length and thereby synchronizes implantation within the population of spotted skunks. Intact, sham-superior cervical ganglionectomized (SCGx), SCGx, and SCGx/bilateral orbitally enucleated (B1) pregnant skunks w...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079x.1986.tb00720.x
更新日期:1986-01-01 00:00:00
abstract::Transgenic rice plants overexpressing a sheep serotonin N-acetyltransferase led to an enhanced production of melatonin with various physiological effects, including seminal root elongation and resistance against cold and oxidative stress, which raises the possibility that melatonin may alter gene expression profiles i...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/jpi.12077
更新日期:2013-11-01 00:00:00
abstract::Carbon tetrachloride (CCl4) exerts its toxic effects by the generation of free radicals. In this study we investigated whether melatonin, a potent free radical scavenger, could prevent the deleterious effects of CCl4. Liver homogenates and liver microsomes were incubated with CCl4 in the presence of melatonin and lipi...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079x.1995.tb00164.x
更新日期:1995-08-01 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::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::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 known neuroprotective actions of melatonin could be due to its antioxidant or radical scavenging activity, or they could be due to specific interactions of the indole with its receptors. A study of structure-activity relationships may provide useful information when a validated macromolecular target has not been (...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1046/j.1600-079x.2003.00102.x
更新日期:2004-03-01 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::Four-week-old male hamsters, born and raised in total darkness or in LD 14:10 (hr) were exposed to several low levels of illumination for 14 weeks. Analyses showed that testicular weights were significantly affected by both photic history and illuminance levels. Animals born in the dark possessed larger testes than th...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079x.1985.tb00641.x
更新日期:1985-01-01 00:00:00
abstract::Melatonin is a powerful antioxidant and free radical scavenger. A large body of in vivo and in vitro evidence shows that melatonin effectively inhibits membrane lipid peroxidation; this damage was based on the measurement of malondialdehyde and/or 4-hydroxynonenal levels. In the current study, for the first time using...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079X.2005.00311.x
更新日期:2006-05-01 00:00:00
abstract::Autophagy is an important survival pathway and participates in the host response to infection. Beneficial effects of melatonin have been previously reported in an animal model of acute liver failure (ALF) induced by the rabbit hemorrhagic disease virus (RHDV). This study was aimed to investigate whether melatonin prot...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/jpi.12124
更新日期:2014-04-01 00:00:00
abstract::We tested whether combined melatonin (Mel) and exendin-4 (Ex4) treatment can better preserve glomerular structural integrity after ischemia-reperfusion (IR) injury compared with either alone. Adult male Sprague Dawley rats (n = 50) were equally divided into sham control (SC), IR, IR-Ex4 (10 μg/kg subcutaneously 30 min...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/jpi.12273
更新日期:2015-11-01 00:00:00
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::Melatonin is an endogenous indoleamine, produced mainly by the pineal gland. Melatonin has been proven to have chronobiotic, antioxidant, antihypertensive, anxiolytic and sedative properties. There are also experimental and clinical data supporting an analgesic role of melatonin. In experimental studies, melatonin sho...
journal_title:Journal of pineal research
pub_type: 杂志文章,评审
doi:10.1111/j.1600-079X.2011.00895.x
更新日期:2011-10-01 00:00:00