Abstract：
:Melatonin has demonstrated a potential protective effect in central nervous system. Thus, it is interesting to determine whether pre-ischemia melatonin administration could protect against cerebral ischemia/reperfusion (IR)-related injury and the underlying molecular mechanisms. In this study, we revealed that IR injury significantly activated endoplasmic reticulum (ER) stress and autophagy in a middle cerebral artery occlusion mouse model. Pre-ischemia melatonin treatment was able to attenuate IR-induced ER stress and autophagy. In addition, with tandem RFP-GFP-LC3 adeno-associated virus, we demonstrated pre-ischemic melatonin significantly alleviated IR-induced autophagic flux. Furthermore, we showed that IR induced neuronal apoptosis through ER stress related signalings. Moreover, IR-induced autophagy was significantly blocked by ER stress inhibitor (4-PBA), as well as ER-related signaling inhibitors (PERK inhibitor, GSK; IRE1 inhibitor, 3,5-dibromosalicylaldehyde). Finally, we revealed that melatonin significantly alleviated cerebral infarction, brain edema, neuronal apoptosis, and neurological deficiency, which were remarkably abolished by tunicamycin (ER stress activator) and rapamycin (autophagy activator), respectively. In summary, our study provides strong evidence that pre-ischemia melatonin administration significantly protects against cerebral IR injury through inhibiting ER stress-dependent autophagy. Our findings shed light on the novel preventive and therapeutic strategy of daily administration of melatonin, especially among the population with high risk of cerebral ischemic stroke.
journal_name
J Pineal Resjournal_title
Journal of pineal researchauthors
Feng D,Wang B,Wang L,Abraham N,Tao K,Huang L,Shi W,Dong Y,Qu Ydoi
10.1111/jpi.12395subject
Has Abstractpub_date
2017-04-01 00:00:00issue
3eissn
0742-3098issn
1600-079Xjournal_volume
62pub_type
杂志文章abstract：:Irradiation of the melatonin metabolite N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK) with UV light of 254 nm causes the release of carbon monoxide (CO) and, thus, deformylation to N(1)-acetyl-5-methoxykynuramine (AMK). Liberation of CO was demonstrated by reduction of PdCl(2) to metallic palladium, under avoidan...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2007.00550.x
更新日期：2008-05-01 00:00:00
abstract：:Sirtuin 1 is a member of the sirtuin family of protein deacetylases, which have attracted considerable attention as mediators of lifespan extension in several model organisms. Induction of sirtuin 1 expression also attenuates neuronal degeneration and death in animal models of Alzheimer's disease and Huntington's dise...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2009.00706.x
更新日期：2009-10-01 00:00:00
abstract：:Earlier studies showed that melatonin reduced the growth of 17-beta-estradiol (E(2))-induced rat pituitary prolactin-secreting tumor (prolactinoma) in vivo. The mechanisms of melatonin's inhibitory action on the prolactin-secreting tumor were further explored by investigating the in vitro effects of melatonin on the g...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2006.00403.x
更新日期：2007-03-01 00:00:00
abstract：:Hypochlorous acid (HOCl) is a potent cytotoxic oxidant generated by the enzyme myeloperoxidase (MPO) in the presence of hydrogen peroxide (H2 O2 ) and chloride (Cl- ). Elevated levels of HOCl play an important role in various pathological conditions through oxidative modification of several biomolecules. Recently, we ...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12463
更新日期：2018-04-01 00:00:00
abstract：:Adult female golden hamsters were used to study the effect of short photoperiod on the endogenous opioid system and the effect of pinealectomy on the serum beta-endorphin-like immunoreactivity (beta-end LI) levels. Hamsters were housed under either long photoperiod (14L:10D) or short photoperiod (2L:22D) and the regul...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1984.tb00211.x
更新日期：1984-01-01 00:00:00
abstract：:The present study analyzes the participation of pineal stalk and superior cervical ganglia (SCG) in the conduction of photic evoked potentials (PEP) to the pineal body (PB) in unanesthetized freely moving rats implanted with semimicroelectrodes. The PEPs were recorded in PB, lateral hypothalamus (LH), and habenular co...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1987.tb00866.x
更新日期：1987-01-01 00:00:00
abstract：:The quantitative autoradiographic 2-[14C]deoxyglucose method was employed to map the metabolic activity of the superior cervical ganglion and the entire brain during unilateral electrical stimulation of the cervical sympathetic trunk in the urethane-anesthetized rat. Stimulation of the cervical sympathetic trunk incre...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1988.tb00768.x
更新日期：1988-01-01 00:00:00
abstract：:Experiments were conducted to determine whether daily melatonin injections could influence reentrainment of circadian locomotor activity rhythms in male Long-Evans rats after phase shifts of the light dark (LD) cycle. When exposed to a 5-h advance of the LD cycle, six out of 15 rats injected daily with melatonin at th...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1988.tb00782.x
更新日期：1988-01-01 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：:Melatonin biosynthesis was examined in Sekiguchi mutant rice lacking functional tryptamine 5-hydroxylase (T5H) activity, which is the terminal enzyme for serotonin biosynthesis in rice. During senescence process, the leaves of Sekiguchi mutant rice produced more tryptamine and N-acetyltryptamine compared with the wild...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2011.00930.x
更新日期：2012-03-01 00:00:00
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：: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：: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：:The protective role of exogenous melatonin on U-induced nephrotoxicity was investigated in rats. Animals were given single doses of uranyl acetate dihydrate (UAD) at 5 mg/kg (subcutaneous), melatonin at 10 or 20 mg/kg (intraperitoneal), and UAD (5 mg/kg) plus melatonin (10 or 20 mg/kg), or vehicle (control group). In ...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2007.00447.x
更新日期：2007-08-01 00:00:00
abstract：:Exposure of rats to light during darkness or blockade of the pineal beta-adrenoceptor in stimulated pineal glands results in a rapid fall in pineal N-acetyltransferase (NAT) activity. Maintenance of a high level of NAT activity requires continuous stimulation of the pineal beta-adrenoceptors. It is not known what fact...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1992.tb00026.x
更新日期：1992-03-01 00:00:00
abstract：:Female Syrian hamsters were kept in a light (14:10 h light:dark cycle, lights on 0600 h)- and temperature (22 or 30 degrees C)-controlled room; some groups were treated with an afternoon s.c. injection of melatonin (6.25, 12.5, or 25 micrograms/day) for 11 or 14 weeks. The melatonin-induced suppression of the reproduc...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1988.tb00656.x
更新日期：1988-01-01 00:00:00
abstract：:The association of seasonal changes in health and disease has been known for centuries. The prevalence of psychopathological symptoms with seasonal fluctuations and the use of melatonin as a biological marker of circadian and circannual rhythms is well documented. The aim of this work was to study the variability of m...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2006.00365.x
更新日期：2006-10-01 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：: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：:A study was carried out to determine the possible influence of melatonin on the proliferation of Kirkman-Robbins hepatoma cells in Syrian hamsters, both in vivo and in vitro. A highly significant inhibition of the proliferation of transplanted hepatoma cells was observed in vivo following melatonin administration (pro...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1992.tb00063.x
更新日期：1992-10-01 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
abstract：:Retinopathy of prematurity is a vision-threatening disease associated with retinal hypoxia-ischemia, leading to the death of retinal neurons and chronic neuronal degeneration. During this study, we used the oxygen-induced retinopathy mice model to mimic retinal hypoxia-ischemia phenotypes to investigate further the ne...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/jpi.12716
更新日期：2021-01-11 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：: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：:An important role for melatonin in bone formation and restructuring has emerged, and studies demonstrate the multiple mechanisms for these beneficial actions. Statistical analysis shows that even with existing osteoporotic therapies, bone-related disease, and mortality are on the rise, creating a huge financial burden...
journal_title：Journal of pineal research
pub_type： 杂志文章,评审
doi：10.1111/jpi.12116
更新日期：2014-03-01 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：: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：:The pineal hormone melatonin, due to its lipophilic nature, has access to every cell and every part of a cell in the body, suggesting that it could exert effects on blood immune cells. The regulation of the activation of monocytes may be important in a number of diseases, especially pathophysiological conditions assoc...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1999.tb00566.x
更新日期：1999-01-01 00:00:00
abstract：:We examined the association between 6-sulphatoxymelatonin (6-SMT) excretion and sleep in 68 volunteers 60-79 years of age who complained of insomnia or depression. An Actillume wrist monitor was worn for 5-7 consecutive days and nights in home-living conditions. Activity was used to estimate total sleep time (TST) and...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079x.1998.tb00526.x
更新日期：1998-04-01 00:00:00
abstract：:Possible role of melatonin in the germination of negatively photoblastic and thermosensitive seeds of Phacelia tanacetifolia Benth was studied. Final germination percentage (FGP) was determined in the presence or absence of light at various temperatures, ranging from 0 to 40°C. The highest FGP was determined as 48.7% ...
journal_title：Journal of pineal research
pub_type： 杂志文章
doi：10.1111/j.1600-079X.2011.00947.x
更新日期：2012-04-01 00:00:00
