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Journal of Pineal Research

Hyoung Yool Lee, Kyoungwhan Back
In plants, melatonin is a potent bioactive molecule involved in the response against various biotic and abiotic stresses. However, little is known of its defensive role against high light (HL) stress. In this study, we found that melatonin was transiently induced in response to HL stress in Arabidopsis thaliana with a simultaneous increase in the expression of melatonin biosynthetic genes, including serotonin N-acetyltransferase1 (SNAT1). Transient induction of melatonin was also observed in the flu mutant, a singlet oxygen (1 O2 )-producing mutant, upon light exposure, suggestive of melatonin induction by chloroplastidic 1 O2 against HL stress...
May 16, 2018: Journal of Pineal Research
Hao Zhou, Dandan Li, Pingjun Zhu, Qiang Ma, Toan Sam, Jin Wang, Shunying Hu, Yundai Chen, Yingmei Zhang
The molecular features of necroptosis in cardiac ischemia reperfusion (IR) injury have been extensively explored. However, there have been no studies investigating the physiological regulatory mechanisms of melatonin acting on necroptosis in cardiac IR injury. This study was designed to determine the role of necroptosis in microvascular IR injury, and investigate the contribution of melatonin in repressing necroptosis and preventing IR-mediated endothelial system collapse. Our results demonstrated that Ripk3 was primarily activated by IR injury and consequently aggravated endothelial necroptosis, microvessel barrier dysfunction, capillary hyperpermeability, the inflammation response, microcirculatory vasospasms and microvascular perfusion defects...
May 16, 2018: Journal of Pineal Research
Diana I Sánchez, Bárbara González-Fernández, Irene Crespo, Beatriz San-Miguel, Marcelino Álvarez, Javier González-Gallego, María Jesús Tuñón
Disruption of circadian rhythms, which are regulated by the circadian clock machinery, plays an important role in different long-term diseases including hepatocellular carcinoma (HCC). Melatonin has been reported to alleviate promotion and progression of HCC, but the potential contribution of circadian clock modulation is unknown. We investigated the effects of melatonin in mice which received diethylnitrosamine (DEN) (35 mg/kg body weight i.p.) once a week for 8 weeks. Melatonin was given at 5 or 10 mg/kg/day i...
May 16, 2018: Journal of Pineal Research
Zhijing Zhang, Eduardo Silveyra, Nange Jin, Christophe P Ribelayga
The C57BL/6J (B6) is the most common inbred mouse strain used in biomedical research in the United States. Yet, this strain is notoriously known for being deficient in the biosynthesis of melatonin, an important effector of circadian clocks in the brain and in the retina. Melatonin deficiency in this strain results from non-functional alleles of the genes coding two key enzymes of the melatonin synthesis pathway: arylalkylamine-N-acetyltransferase (Aanat) and N-acetylserotonin-O-methyltransferase (Asmt). By introducing functional alleles of the Aanat and Asmt genes from the melatonin-proficient CBA/CaJ (CBA) mouse strain to B6, we have generated a B6 congenic line that has acquired the capacity of rhythmic melatonin synthesis...
May 16, 2018: Journal of Pineal Research
Sebastian R Hobson, Seshi Gurusinghe, Rebecca Lim, Nicole O Alers, Suzanne L Miller, John C Kingdom, Euan M Wallace
Preeclampsia remains a leading cause of maternal and perinatal morbidity and mortality. There have been no material advances in the treatment of preeclampsia for nearly 50 years. Combining in vitro studies and a clinical trial, we aimed to determine if melatonin could be a useful adjuvant therapy. In a xanthine/xanthine oxidase (X/XO) placental explant model, melatonin reduced oxidative stress (8-isoprostane) and enhanced antioxidant markers (Nrf2 translocation, HO-1), but did not affect explant production of anti-angiogenic factors (sFlt, sEng, activin A)...
May 16, 2018: Journal of Pineal Research
Ko-Hsiu Lu, Shih-Chi Su, Chiao-Wen Lin, Yi-Hsien Hsieh, Ya-Chiu Lin, Ming-Hsien Chien, Russel J Reiter, Shun-Fa Yang
Osteosarcoma, with its high metastatic potential, is the most prevalent malignant bone tumor in children and adolescents. Melatonin possesses multiple tumor-suppressing properties for a myriad of tumors, but little is known about the effects of melatonin on osteosarcoma metastasis. In this study, we demonstrated that melatonin elicited very low cytotoxicity and significantly inhibited cellular motility, migration, and invasion in human osteosarcoma U2OS and HOS cells. Moreover, using RNA sequencing technology, we revealed that melatonin repressed C-C motif chemokine ligand 24 (CCL24) gene expression in U2OS cells...
May 16, 2018: Journal of Pineal Research
Mihir Kumar Mandal, Haktan Suren, Brian Ward, Arezue Boroujerdi, Chandrasekar Kousik
Since the 1950s, research on the animal neurohormone melatonin, has focused on its multi-regulatory effect on patients suffering from insomnia, cancer, and Alzheimer's. In plants, melatonin plays major role in plant growth and development, and is inducible in response to diverse biotic and abiotic stresses. However, studies on the direct role of melatonin in disease suppression and as a signaling molecule in host-pathogen defense mechanism are lacking. This study provides insight on the predicted biosynthetic pathway of melatonin in watermelon (Citrullus lanatus) and how application of melatonin, an environmental-friendly immune inducer, can boost plant immunity and suppress pathogen growth where fungicide resistance and lack of genetic resistance are major problems...
May 15, 2018: Journal of Pineal Research
Zhuo Wang, Ya-Hong Zhang, Wei Zhang, Hui-Ling Gao, Man-Li Zhong, Ting-Ting Huang, Rui-Fang Guo, Na-Na Liu, Dan-Dan Li, Yin Li, Zhan-You Wang, Pu Zhao
Copper is essential for the generation of reactive oxygen species (ROS), which are induced by amyloid-β (Aβ) aggregation; thus, the homeostasis of copper is believed to be a therapeutic target for Alzheimer's disease (AD). Although clinical trials of copper chelators show promise when applied in AD, the underlying mechanism is not fully understood. Here, we reported that copper chelators promoted non-amyloidogenic processing of AβPP through MT1/2 /CREB-dependent signaling pathways. First, we found that the formation of Aβ plaques in the cortex was significantly reduced, and learning deficits were significantly improved in AβPP/PS1 transgenic mice by copper chelator tetrathiomolybdate (TM) administration...
April 30, 2018: Journal of Pineal Research
Jian Wei, Dong-Xu Li, Jia-Rong Zhang, Chi Shan, Zed Rengel, Zhong-Bang Song, Qi Chen
Melatonin has been detected in plants in 1995; however, the function and signaling pathway of this putative phytohormone are largely undetermined due to a lack of knowledge about its receptor. Here, we discovered the first phytomelatonin receptor (CAND2/PMTR1) in Arabidopsis thaliana and found that melatonin governs the receptor-dependent stomatal closure. The application of melatonin induced stomatal closure through the heterotrimeric G protein α subunit-regulated H2 O2 and Ca2+ signals. The Arabidopsis mutant lines lacking AtCand2 that encodes a candidate G-protein coupled receptor were insensitive to melatonin-induced stomatal closure...
April 27, 2018: Journal of Pineal Research
Cezary Skobowiat, Anna A Brożyna, Zorica Janjetovic, Jeayeng Saowanee, Allen S W Oak, Tae-Kang Kim, Uraiwan Panich, Russel J Reiter, Andrzej T Slominski
Melatonin and its derivatives [N1 -acetyl-N2 -formyl-5-methoxykynurenine (AFMK) and N-acetyl serotonin (NAS)] have broad spectrum protective effects against photocarcinogenesis, including both direct and indirect antioxidative actions, regulation of apoptosis and DNA damage repair; these data were primarily derived from in vitro models. This study evaluates possible beneficial effects of melatonin and its active derivatives against UVB-induced harm to human and porcine skin ex vivo and to cultured HaCaT cells...
April 27, 2018: Journal of Pineal Research
Teng Zhang, Yang Zhou, Lan Li, Yong Zhao, Massimo De Felici, Russel J Reiter, Wei Shen
A growing number of couples experience fertility issues with almost half being due to male factors. The exposure to toxic environmental contaminants, such as endocrine disruptors (EDs), has been shown to negatively affect male fertility. EDs are present in the environment and exposure to these toxins results in the failure of spermatogenesis. The deleterious effects of EDs on spermatogenesis have been well documented, whereas improvement of infertility associated with spermatogenesis defects remains a great challenge...
April 14, 2018: Journal of Pineal Research
Rishi Sharma, Pradeep Sahota, Mahesh M Thakkar
Melatonin promotes sleep. However, the underlying mechanisms are unknown. Orexin neurons in the perifornical lateral hypothalamus (PFH) are pivotal for wake promotion. Does melatonin promote sleep by inhibiting orexin neurons? We used C57BL/6J mice and designed 4 experiments to address this question. Experiment 1 used double-labeled immunofluorescence and examined the presence of melatonin receptors on orexin neurons. Second, mice, implanted with bilateral guides targeted toward PFH and sleep-recording electrodes, were infused with melatonin (500 pmole/50 nL/side) at dark onset (onset of active period), and spontaneous bouts of sleep-wakefulness were examined...
April 14, 2018: Journal of Pineal Research
Hyemin Lee, Hyo-Jung Lee, Ji Hoon Jung, Eun Ah Shin, Sung-Hoon Kim
Here the underlying antitumor mechanism of melatonin and its potency as a sensitizer of Paclitaxel was investigated in X02 cancer stem cells. Melatonin suppressed sphere formation and induced G2/M arrest in X02 cells expressing Nestin, CD133, CXCR4 and SOX-2 as biomarkers of stemness. Furthermore, melatonin reduced the expression of CDK2, CDK4, cyclin D1, cyclin E, and c-Myc and upregulated cyclin B1 in X02 cells. Notably, genes of c-Myc related mRNAs were differentially expressed in melatonin treated X02 cells by microarray analysis...
April 14, 2018: Journal of Pineal Research
Ok Jin Hwang, Kyoungwhan Back
Serotonin N-acetyltransferase (SNAT) is the penultimate enzyme in melatonin biosynthesis catalyzing the conversion of serotonin into N-acetylserotonin. In plants, SNAT is encoded by two isogenes of which SNAT1 is constitutively expressed and its overexpression confers increased yield in rice. However, the role of SNAT2 remains to be clarified. In contrast to SNAT1, the diurnal rhythm of SNAT2 mRNA expression peaks at night. In this study, transgenic rice plants in which SNAT2 expression was suppressed by RNAi technology showed a decrease in melatonin and a dwarf phenotype with erect leaves, reminiscent of brassinosteroids (BRs)-deficient mutants...
April 1, 2018: Journal of Pineal Research
Haitao Shi, Shengmin Zhang, Daozhe Lin, Yunxie Wei, Yu Yan, Guoyin Liu, Russel J Reiter, Zhulong Chan
Although accumulating evidence demonstrates the crosstalk between melatonin and auxin as derivatives of tryptophan, the underlying signaling events remain unclear. In this study, we found that melatonin and auxin mediated the transcriptional levels of zinc finger of Arabidopsis thaliana (ZAT6) in a mutually antagonistic manner. ZAT6 negatively modulated the endogenous auxin level, and ZAT6 knockdown plants were less sensitive to melatonin-regulated auxin biosynthesis, indicating its involvement in melatonin-mediated auxin accumulation...
April 1, 2018: Journal of Pineal Research
Jee-In Heo, Dae Wui Yoon, Ji Hee Yu, Nam Hoon Kim, Hye Jin Yoo, Ji A Seo, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Dong Seop Choi, Nan Hee Kim
Melatonin plays an important role in regulating circadian rhythms. It also acts as a potent anti-oxidant and regulates glucose and lipid metabolism, although the exact action mechanism is not clear. The α2-HS-glycoprotein gene (AHSG) and its protein, fetuin-A (FETUA) is one of the hepatokines and is known to be associated with insulin resistance and type 2 diabetes. The aim of this study was to determine whether melatonin improves hepatic insulin resistance and hepatic steatosis in a FETUA-dependent manner...
April 1, 2018: Journal of Pineal Research
Shumin Zhang, Sen Liu, Jiankui Zhang, Russel J Reiter, Ying Wang, Dan Qiu, Xiumei Luo, A Rehman Khalid, Hanyan Wang, Li Feng, Zhenghong Lin, Maozhi Ren
Human health, food safety and agriculture have been threatened by oomycetic diseases caused by notorious pathogenic oomycetes. Chemical oomyceticides are the main approaches in control of pathogenic oomycetes. However, the overused chemical oomyceticides have resulted in serious environmental pollution and drug resistance. The eco-friendly bio-oomyceticides are required for sustainable development through screening synergistic drug combinations. In this study, Phytophthora nicotianae (P. nicotianae), as one of the most destructive oomycetic diseases in agriculture, was used as a model system to screen the novel bio-oomyceticides based on drug combination...
March 25, 2018: Journal of Pineal Research
Mingge Ding, Na Feng, Daishi Tang, Jiahao Feng, Zeyang Li, Min Jia, Zhenhua Liu, Xiaoming Gu, Yuemin Wang, Feng Fu, Jianming Pei
Myocardial contractile dysfunction is associated with an increase in mitochondrial fission in patients with diabetes. However, whether mitochondrial fission directly promotes diabetes-induced cardiac dysfunction is still unknown. Melatonin exerts a substantial influence on the regulation of mitochondrial fission/fusion. This study investigated whether melatonin protects against diabetes-induced cardiac dysfunction via regulation of mitochondrial fission/fusion and explored its underlying mechanisms. Here, we show that melatonin prevented diabetes-induced cardiac dysfunction by inhibiting dynamin-related protein 1 (Drp1)-mediated mitochondrial fission...
March 25, 2018: Journal of Pineal Research
Fan-Yen Lee, Cheuk-Kwan Sun, Pei-Hsun Sung, Kuan-Hung Chen, Sarah Chua, Jiunn-Jye Sheu, Sheng-Ying Chung, Han-Tan Chai, Yi-Ling Chen, Tien-Hung Huang, Chi-Ruei Huang, Yi-Chen Li, Chi-Wen Luo, Hon-Kan Yip
We tested the hypothesis that daily melatonin treatment protects endothelial lineage and functional integrity against the aging process, oxidative stress/endothelial denudation (ED), and toxic environment and restored blood flow in murine critical limb ischemia (CLI). In vitro study using HUVECs, in vivo models (ie, CLI through left femoral artery ligation and ED through carotid artery wire injury), and model of lipopolysaccharide-induced aortic injury in young (3 months old) and aged (8 months old) mice were used to elucidate effects of melatonin treatment on vascular endothelial integrity...
March 23, 2018: Journal of Pineal Research
Amanda Lochner, Erna Marais, Barbara Huisamen
Melatonin is a pleiotropic hormone with several functions. It binds to specific receptors and to a number of cytosolic proteins, activating a vast array of signalling pathways. Its potential to protect the heart against ischaemia/reperfusion damage has attracted much attention, particularly in view of its possible clinical applications. This review will focus mainly on the possible signalling pathways involved in melatonin-induced cardioprotection. In particular, the role of the melatonin receptors and events downstream of receptor activation, for example, the Reperfusion Injury Salvage Kinase (RISK), Survivor Activating Factor Enhancement (SAFE) and Notch pathways, the sirtuins, nuclear factor E2-related factor 2 (Nrf2) and translocases in the outer membrane (TOM70) will be discussed...
March 23, 2018: Journal of Pineal Research
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