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 protection against liver injury induced by the RHDV associates to modulation of autophagy. Rabbits were infected with 2 × 10(4) hemagglutination units of a RHDV isolate and received 20 mg/kg melatonin at 0, 12, and 24 hr postinfection. RHDV induced autophagy, with increased expression of beclin-1, ubiquitin-like autophagy-related (Atg)5, Atg12, Atg16L1 and sequestrosome 1 (p62/SQSTM1), protein 1 light chain 3 (LC3) staining, and conversion of LC3-I to autophagosome-associated LC3-II. These effects reached a maximum at 24 hr postinfection, in parallel to extensive colocalization of LC3 and lysosome-associated membrane protein (LAMP)-1. The autophagic response induced by RHDV infection was significantly inhibited by melatonin administration. Melatonin treatment also resulted in decreased immunoreactivity for RHDV viral VP60 antigen and a significantly reduction in RHDV VP60 mRNA levels, oxidized to reduced glutathione ratio (GSSG/GSH), caspase-3 activity, and immunoglobulin-heavy-chain-binding protein (BiP) and CCAAT/enhancer-binding protein homologous protein (CHOP) expression. Results indicate that, in addition to its antioxidant and antiapoptotic effects, and the suppression of ER stress, melatonin induces a decrease in autophagy associated with RHDV infection and inhibits RHDV RNA replication. Results obtained reveal novel molecular pathways accounting for the protective effect of melatonin in this animal model of ALF.
journal_name
J Pineal Resjournal_title
Journal of pineal researchauthors
San-Miguel B,Crespo I,Vallejo D,Álvarez M,Prieto J,González-Gallego J,Tuñón MJdoi
10.1111/jpi.12124subject
Has Abstractpub_date
2014-04-01 00:00:00pages
313-21issue
3eissn
0742-3098issn
1600-079Xjournal_volume
56pub_type
杂志文章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 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::We tested the hypothesis that melatonin (Mel) enhances exogenous mitochondria (Mito) treatment against rodent hepatic ischemia-reperfusion (IR) injury. In vitro study utilized three groups of hepatocytes (i.e. nontreatment, menadione, and menadione-melatonin treatment, 4.0 × 10(5) each), while in vivo study used adult...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/jpi.12326
更新日期:2016-08-01 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::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::The effect of melatonin injection on Freund's adjuvant-induced changes in levels and 24-hr rhythms of circulating ACTH, growth hormone (GH), prolactin (PRL), luteinizing hormone (LH), and insulin was assessed in rats. Animals received subcutaneous (s.c.) injections of melatonin (30 microg) or vehicle, 1 hr before ligh...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079x.1999.tb00592.x
更新日期:1999-08-01 00:00:00
abstract::The effect of melatonin (0.1 microM) on freshly isolated islets from adult rats was investigated. Melatonin caused a marked decrease of insulin secretion by islets in response to glucose. The mechanism involved was then examined. Melatonin did not interfere with glucose metabolism as indicated by the measurement of gl...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1034/j.1600-079x.2002.02903.x
更新日期:2002-10-01 00:00:00
abstract::Melatonin has previously been shown to be neuroprotective in rodent models of ischemic stroke. Herein, we tested whether this antioxidant may also be suitable for prophylactic use against stroke. To clarify this issue, melatonin was administrated orally for 9 wk (4 mg/kg/day) in mice and its effects on subsequent inju...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079X.2004.00162.x
更新日期:2004-11-01 00:00:00
abstract::The objective of this study was to determine the role of alpha-adrenoceptors in melatonin production by rat pineal gland. Pineal glands were isolated from adult male rats and maintained in organ baths. The perfusate was sampled every 5 min, stored, and later assayed for melatonin. Exposure to norepinephrine (10 microM...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1034/j.1600-079x.2002.01842.x
更新日期:2002-05-01 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::Epigenetic alterations have emerged as an important mechanism involved in tumorigenesis. The epigenetic impact of DNA methylation in various types of human cancer is not completely understood. Previously, we observed melatonin-induced differential expression of miRNA and miRNA-related genes in human breast cancer cell...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079X.2012.01027.x
更新日期:2013-01-01 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::Melatonin as a potent antioxidant exhibits important nutritional and medicinal values. To produce melatonin-enriched milk will benefit the consumers. In this study, a sheep bioreactor which generates melatonin-enriched milk has been successfully developed by the technology that combined CRISPR/Cas9 system and microinj...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/jpi.12406
更新日期:2017-08-01 00:00:00
abstract::Methamphetamine (METH) is a potent psychostimulant drug that may cause neuronal cell degeneration. The underlying mechanisms of METH-induced neuronal toxicity remains poorly understood. In this study, we investigated an important role of calpain-dependent cascades in methamphetamine-induced toxicity in human dopaminer...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079X.2009.00731.x
更新日期:2010-03-01 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::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 inju...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/jpi.12395
更新日期:2017-04-01 00:00:00
abstract::Dim light exposure of the mother during pregnancy has been proposed as one of the environmental factors that affect the fetal brain development in schizophrenia. Melatonin circulating levels are regulated by the environmental light/dark cycle. This hormone stimulates neuronal differentiation in the adult brain. Howeve...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/jpi.12421
更新日期:2017-10-01 00:00:00
abstract::Constitutive activation and gemcitabine induction of nuclear factor-κB (NF-κB) contribute to the aggressive behavior and chemotherapeutic resistance of pancreatic ductal adenocarcinoma (PDAC). Thus, targeting the NF-κB pathway has proven an insurmountable challenge for PDAC therapy. In this study, we investigated whet...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/jpi.12285
更新日期:2016-01-01 00:00:00
abstract::Chronic hyperhomocysteinemia is a risk factor in cardiovascular diseases and neurodegeneration. Among the putative mechanisms of homocysteine-induced neurotoxicity, an increased production of reactive oxygen species has been suggested. However, elevated homocysteine levels might disturb neurogenesis during brain devel...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079X.2007.00506.x
更新日期:2008-03-01 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::The effect of various cations on activity of hydroxyindole-O-methyltransferase (HIOMT) and N-acetyltransferase (NAT) from pineal gland was studied. Copper inhibited both enzymes while calcium and magnesium inhibited HIOMT; the mechanisms of these inhibitions are unknown at this stage. Calcium, magnesium, potassium, an...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079x.1987.tb00852.x
更新日期:1987-01-01 00:00:00
abstract::Recently, a species-dependent distribution of melatonin binding sites have been found in lamina I-V and lamina X of the spinal cord. In order to learn more about the function of spinal melatonin receptors, we investigated (i) the gene expression for melatonin receptor subtypes in lumbar and thoracal spinal cord tissue...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1034/j.1600-079x.2003.00047.x
更新日期:2003-08-01 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::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::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::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::The circadian system comprises several peripheral oscillators and a central rhythm generator that, in mammals, is located in the suprachiasmatic nucleus of the hypothalamus. Expression of clock genes is a characteristic feature of the central rhythm generator and the peripheral oscillators. With regard to the rhythmic...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/j.1600-079X.2005.00279.x
更新日期:2006-01-01 00:00:00
abstract::Melatonin has been proposed as a possible treatment for the deleterious effects of hypoxia/reoxygenation (H/R), such as autophagy, inflammation, and apoptosis. Pathological pregnancies, such as preeclampsia, are associated with placental H/R, and decreased placental melatonin synthesis as well as lower melatonin level...
journal_title:Journal of pineal research
pub_type: 杂志文章
doi:10.1111/jpi.12520
更新日期:2018-11-01 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::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