Journal of Pineal Research最新文献

{"title":"Melatonin Affects Peucedanum praeruptorum Vegetative Growth and Coumarin Synthesis by Modulating the Antioxidant System, Photosynthesis, and Endogenous Hormones","authors":"Xiaoting Wan,&nbsp;Yingyu Zhang,&nbsp;Guoyu Wang,&nbsp;Ranran Liao,&nbsp;Haoyu Pan,&nbsp;Cunwu Chen,&nbsp;Bangxing Han,&nbsp;Hui Deng,&nbsp;Cheng Song","doi":"10.1111/jpi.70018","DOIUrl":"10.1111/jpi.70018","url":null,"abstract":"<div>\u0000 \u0000 <p>The dried root of <i>Peucedanum praeruptorum</i> is often used medicinally and has high pyran- and furanocoumarin content. Although exogenous melatonin (MT) impacts the regulation of plant growth, stress responses, secondary metabolism, etc., it remains unclear whether MT regulates the vegetative growth and development of <i>P. praeruptorum</i>. Thus, the aim of the current study is to characterize the effects of different exogenous MT concentrations on the physiological functions, photosynthesis, antioxidant systems, hormone induction, and coumarin synthesis of <i>P. praeruptorum</i>. Different MT concentrations exert distinct regulatory effects on <i>P. praeruptorum</i> growth and the expression of genes related to coumarin synthesis. Treatment of <i>P. praeruptorum</i> with low concentrations of MT increases photosynthesis and leaf growth compared to the control, while high concentrations reduce root vitality and elongation and decrease the expression of photosynthetic system genes. Low concentrations of MT also significantly increase antioxidant enzyme activity and photosynthetic pigment content and modulate the levels of IAA, gibberellic acid, salicylic acid, jasmonic acid, abscisic acid, and endogenous MT. Moreover, MT increases the activity of the MT synthesis enzymes tryptophan decarboxylase, tryptophan hydroxylase, tryptamine-5-hydroxylase, serotonin <i>N</i>-acetyltransferase, acetylserotonin <i>O</i>-methyltransferase, and caffeic acid <i>O</i>-methyltransferase, and promotes the accumulation of isoscopoletin, scopoletin, peucedanocoumarin II, praeruptorin A, praeruptorin B, and praeruptorin E. MT also upregulates most genes associated with coumarin synthesis, including <i>PAL1</i>, <i>C4H</i>, <i>4CL-3</i>, <i>C3H-1</i>, <i>F6H-1</i>, <i>CCoAMT</i>, <i>OMT-1</i>, <i>CYP71AJ1</i>, <i>CYP84A1-1</i>, <i>S8H-1</i>, <i>PT-1</i>, and <i>COSY-1</i>. These findings demonstrate that MT may improve <i>P. praeruptorum</i> growth and development while promoting the synthesis of coumarin components.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin Inhibits Endometriosis Growth via Specific Binding and Inhibition of EGFR Phosphorylation","authors":"Yiran Li,&nbsp;Sze-Wan Hung,&nbsp;Xu Zheng,&nbsp;Yang Ding,&nbsp;Tao Zhang,&nbsp;Zhouyurong Tan,&nbsp;Ruizhe Zhang,&nbsp;Yuezhen Lin,&nbsp;Yi Song,&nbsp;Yao Wang,&nbsp;Chi-Chiu Wang","doi":"10.1111/jpi.70022","DOIUrl":"10.1111/jpi.70022","url":null,"abstract":"<p>As a chronic gynecological disease, endometriosis is defined as the implantation of endometrial glands as well as stroma outside the uterine cavity. Proliferation is a major pathophysiology in endometriosis. Previous studies demonstrated a hormone named melatonin, which is mainly produced by the pineal gland, exerts a therapeutic impact on endometriosis. Despite that, the direct binding targets and underlying molecular mechanism have remained unknown. Our study revealed that melatonin treatment might be effective in inhibiting the growth of lesions in endometriotic mouse model as well as in human endometriotic cell lines. Additionally, the drug–disease protein–protein interaction (PPI) network was built, and epidermal growth factor receptor (EGFR) was identified as a new binding target of melatonin treatment in endometriosis. Computational simulation together with BioLayer interferometry was further applied to confirm the binding affinity. Our result also showed melatonin inhibited the phosphorylation level of EGFR not only in endometriotic cell lines but also in mouse models. Furthermore, melatonin inhibited the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)—protein kinase B (Akt) pathway and arrested the cell cycle via inhibiting CyclinD1 (CCND1). In vitro and in vivo knockdown/restore assays further demonstrated the involvement of the binding target and signaling pathway that we found. Thus, melatonin can be applied as a novel therapy for the management of endometriosis.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zebrafish Dark-Dependent Behavior Requires Phototransduction by the Pineal Gland","authors":"Yair Wexler,&nbsp;Dengfeng Huang,&nbsp;Adar Medvetzky,&nbsp;Daniel Armbruster,&nbsp;Wolfgang Driever,&nbsp;Jun Yan,&nbsp;Yoav Gothilf","doi":"10.1111/jpi.70021","DOIUrl":"10.1111/jpi.70021","url":null,"abstract":"<p>Located dorsally underneath a thin translucent skull in many teleosts, the pineal gland is a photoreceptive organ known as a key element of the circadian clock system. Nevertheless, the presence of additional routes of photoreception presents a challenge in determining its specific roles in regulating photic-related behavior. Here, we show the importance of the pineal gland in mediating a prolonged motor response of zebrafish larvae to sudden darkness, both as a photodetector and as a circadian pacemaker. This was evident by a reduced motor response of Bsx-deficient larvae, lacking a pineal gland, to sudden darkness. Moreover, the typical daily rhythm of the intensity of this response was lost in the pineal-less larvae. In contrast, motor response to a sudden increase in illumination was unaffected. Furthermore, we show that the pineal-mediated behavioral response to darkness requires two elements: the photoreceptor cells and the projecting neurons. Dark response was impaired in larvae whose pineal photoreceptor cells were genetically ablated and in larvae whose pineal projecting neurons had undergone laser-axotomy. This study thus establishes the pineal gland as a mediator of dark-dependent behavior and reveals underlying cellular components involved in transducing information about darkness to the brain.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3-Month Melatonin Supplementation to Reduce Brain Oxidative Stress and Improve Sleep in Mild Cognitive Impairment: A Randomised Controlled Feasibility Trial","authors":"Zoe Menczel Schrire,&nbsp;Craig L. Phillips,&nbsp;Shantel L. Duffy,&nbsp;Nathaniel S. Marshall,&nbsp;Loren Mowszowski,&nbsp;Haley M. La Monica,&nbsp;Lachlan Stranks,&nbsp;Christopher J. Gordon,&nbsp;Julia L. Chapman,&nbsp;Bandana Saini,&nbsp;Sharon L. Naismith,&nbsp;Ronald R. Grunstein,&nbsp;Camilla M. Hoyos","doi":"10.1111/jpi.70019","DOIUrl":"10.1111/jpi.70019","url":null,"abstract":"<div>\u0000 \u0000 <p>Melatonin has multiple proposed therapeutic benefits including antioxidant properties, circadian rhythm synchronisation and sleep promotion. Since these areas are also recognised risk factors for dementia, melatonin has been hypothesised to slow cognitive decline in older adults.</p>\u0000 <p>Participants with Mild Cognitive Impairment (MCI) were recruited from the community for a 12-week randomised placebo-controlled parallel, feasibility trial of 25 mg oral melatonin nightly. Primary outcomes were feasibility, acceptability, and tolerability. Secondary efficacy outcomes were brain oxidative stress, cognition, mood, and sleep at 12 weeks.</p>\u0000 <p>Forty participants (mean [SD] age = 68.2 [4.7] years; 19 female) were randomised. Feasibility, defined as those who met eligibility criteria, was 42/389, 11%. Acceptability, determined by the proportion of eligible people who agreed to be randomised, was 40/44, 91%. Tolerability, determined by adherence to the nightly melatonin and completion of the main secondary outcome (Magnetic Resonance Spectroscopy scan) was over the pre-defined 80% threshold for all participants. The study was not powered to detect effectiveness. Accordingly, there were no significant differences between melatonin and placebo interventions in any of the secondary outcomes.</p>\u0000 <p>The protocol was developed, and successfully implemented, with the planned number of eligible participants recruited. All participants were able to complete all aspects of the trial, including online visits and assessments, with no differences in adverse events between groups. This is promising for future trials, which should conduct the study with a larger sample size and longer duration to yield necessary efficacy data.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skeletal Phenotyping of Period-1-Deficient Melatonin-Proficient Mice","authors":"Olaf Bahlmann,&nbsp;Shahed Taheri,&nbsp;Manuela Spaeth,&nbsp;Katrin Schröder,&nbsp;Arndt F. Schilling,&nbsp;Christian Dullin,&nbsp;Erik Maronde","doi":"10.1111/jpi.70020","DOIUrl":"10.1111/jpi.70020","url":null,"abstract":"<p>In mice, variability in adult bone size and density has been observed among common inbred strains. Also, in the group of genes regulating circadian rhythmicity in mice, so called clock genes, changes in body size and skeletal parameters have been noted in knockout mice. Here, we studied the size and density of prominent bones of the axial and appendicular skeleton of clock gene <i>Period</i>-1-deficient (<i>Per</i>1^-/-) mice by means of microcomputed tomography. Our data show shorter spinal length, smaller and less dense femora and tibiae, but no significant changes in the shape of the skull and the length of the head. Together with the significantly lower total body weight of <i>Per</i>1^-/- mice, we conclude that <i>Per</i>1-deficiency in a melatonin-proficient mouse strain is associated with an altered body phenotype with smaller appendicular (hind limb) bone size, shorter spine length and lower total body weight while normal head length and brain weight. The observed changes suggest an involvement of secondary bone mineralisation with impact on long bones, but lesser impact on those of the skull. Evidence and overall physiological implications of these findings are discussed.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Predictors of Shift Work Adaptation and Its Association With Immune, Hormonal and Metabolite Biomarkers","authors":"Barbara N. Harding,&nbsp;Ana Espinosa,&nbsp;Gemma Castaño-Vinyals,&nbsp;Oscar J. Pozo,&nbsp;Debra J. Skene,&nbsp;Mariona Bustamante,&nbsp;Maria Mata,&nbsp;Ruth Aguilar,&nbsp;Carlota Dobaño,&nbsp;Valentin Wucher,&nbsp;José Maria Navarrete,&nbsp;Patricia Such Faro,&nbsp;Antonio Torrejón,&nbsp;Manolis Kogevinas,&nbsp;Kyriaki Papantoniou","doi":"10.1111/jpi.70017","DOIUrl":"10.1111/jpi.70017","url":null,"abstract":"<p>We explored predictors of shift work adaptation and how it relates to disease risk biomarker levels. These analyses included 38 male, rotating shift workers, sampled twice at the end of a 3-week night shift and a 3-week day shift rotation. Participants collected all 24-h urine voids, wore activity sensors, and responded to questionnaires during each shift. Using cosinor analysis, we derived the main period of urinary 6-sulfatoxymelatonin (aMT6s) production. Adaptation was defined as the overlap between the main aMT6s production period and sleep period assessed with actigraphy. We used linear models to identify predictors of adaptation to each shift and assessed associations between adaptation profiles and hormone, cytokine, and metabolite biomarker levels. The median duration of overlap (adaptation) was 3.85 h (IQR 2.59–5.03) in the night and 2.98 (IQR 2.17–4.11) in the day shift. In the night shift, a later chronotype (coeff: −1.16, 95% CI −1.87, −0.45) and increased light at night (coeff: −0.97, 95% CI −1.76, −0.18) were associated with poorer adaptation, while longer sleep duration was associated with better adaptation (coeff: 0.46, 95% CI 0.04, 0.88). In the day shift, later sleep onset was associated with worse adaptation (coeff: −0.06, 95% CI −0.12, −0.01), while longer sleep duration was associated with better adaptation (coeff: 0.54, 0.26, 0.81). Results suggest higher androgen and inflammatory marker levels and lower levels of several metabolite markers among less adapted individuals. Chronotype, sleep, and light at night were all associated with night or day shift adaptation. Given the small sample size, results should be viewed as exploratory, but may inform interventions to optimize adaptation of rotating shift workers.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of the Melatonin Receptor MT1 by the Natural Product Gastrodin to Promote Sleep","authors":"Lijing Zhang,&nbsp;Mengli Lan,&nbsp;Hui Chen,&nbsp;Richard Ward,&nbsp;Ya Zhao,&nbsp;Jing Guo,&nbsp;Lang Xiong,&nbsp;Xiuyu Yang,&nbsp;Yuxuan Pu,&nbsp;Cheng Xiang,&nbsp;Su An,&nbsp;Xiaoxi Guo,&nbsp;Tian-Rui Xu,&nbsp;Yang Yang","doi":"10.1111/jpi.70016","DOIUrl":"10.1111/jpi.70016","url":null,"abstract":"<div>\u0000 \u0000 <p>The activation of melatonin receptors, belonging to the G-protein coupled receptors (GPCRs) superfamily, has been recognized as a vital approach in the clinical management of sleep disorders. Although the natural agonist melatonin and synthetic agonists (e.g., ramelteon) targeting these receptors have been extensively studied, the identification of natural compounds acting as ligands remains elusive. We applied a combination of methods including GPCR-induced ERK1/2 MAP kinase phosphorylation assay, inhibition of forskolin-stimulated cAMP production, drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), solvent-induced protein precipitation (SIP), 2-[¹²⁵I]-iodomelatonin binding assay, fluorescence resonance energy transfer (FRET), and molecular docking to investigate MT₁ activation by gastrodin and the gastrodin–MT₁ interaction. The in vivo study was performed with mice whose MT₁ receptors were knocked down in the suprachiasmatic nucleus (SCN) of the brain. The sleep behavior and sleep-related hypothalamic neurotransmitters were evaluated. The results identified that the gastrodin acted as an agonist of MT₁ through direct binding to the receptor. The interaction of gastrodin-MT₁ was similar to that of melatonin–MT₁. The in vivo sleep-promoting effect of the gastrodin depended on the presence of MT₁ in the SCN and was associated with the hypothalamic neurotransmitters, similarly to melatonin.</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-Specific Metabolic Effects of Gestational Chronodisruption and Maternal Melatonin Supplementation in Rat Offspring","authors":"Natalia Méndez,&nbsp;Fernando Corvalan,&nbsp;Diego Halabi,&nbsp;Abigail Vasquez,&nbsp;Karina Vergara,&nbsp;Hector Noriega,&nbsp;Pamela Ehrenfeld,&nbsp;Katiushka Sanhueza,&nbsp;Maria Seron-Ferre,&nbsp;Guillermo J. Valenzuela,&nbsp;Claudia Torres-Farfan","doi":"10.1111/jpi.70015","DOIUrl":"10.1111/jpi.70015","url":null,"abstract":"<div>\u0000 \u0000 <p>Gestational chronodisruption, increasingly common due to irregular light exposure, disrupts maternal-fetal circadian signaling, leading to long-term health issues in offspring. We utilized a chronic photoperiod shifting model (CPS) in pregnant rats to induce chronodisruption and investigated the potential mitigating effects of maternal melatonin supplementation (CPS + Mel). Male and female offspring were evaluated at 3 ages (90, 200, and 400 days of age) for metabolic profiles, hormonal responses, cytokine levels, and adipose tissue activity. Our findings indicate that gestational chronodisruption leads to increased birth weight by approximately 15% in male and female offspring and increased obesity prevalence in male offspring, accompanied by a 30% reduction in nocturnal melatonin levels and a significant disruption in corticosterone rhythms. Male CPS offspring also exhibited decreased lipolytic activity in white adipose tissue, with a 25% reduction in glycerol release compared to controls, indicating impaired metabolic flexibility. In contrast, female offspring, while less affected metabolically, showed a 25% increase in adipose tissue lipolytic activity and higher levels of pro-inflammatory cytokines such as IL-6 (increased by 40%). Scheduled melatonin supplementation in chronodisrupted mothers, administered throughout gestation, effectively normalized birth weights in both sexes, reduced obesity prevalence in males by 18%, and improved lipolytic activity in male offspring, bringing it closer to control levels. In females, melatonin supplementation moderated cytokine levels, reducing IL-6 by 35% and restoring IL-10 levels to near-control values. These results highlight the importance of sex-specific prenatal interventions, particularly the role of melatonin in preventing disruptions to fetal metabolic and inflammatory pathways caused by gestational chronodisruption. Melatonin treatment would prevent maternal circadian rhythm misalignment, thereby supporting healthy fetal development. This study opens new avenues for developing targeted prenatal care strategies that align maternal and fetal circadian rhythms, mitigating the long-term health risks associated with chronodisruption during pregnancy.</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parkin-TLR4-NLRP3 Axis Directs Melatonin to Alleviate Atrazine-Induced Immune Impairment in Splenic Macrophages","authors":"Shuo Liu,&nbsp;Tian-Ning Yang,&nbsp;Yu-Xiang Wang,&nbsp;Xiang-Yu Ma,&nbsp;Yu-Sheng Shi,&nbsp;Yi Zhao,&nbsp;Jin-Long Li","doi":"10.1111/jpi.70014","DOIUrl":"10.1111/jpi.70014","url":null,"abstract":"<div>\u0000 \u0000 <p>Atrazine (ATR) is a widespread environmental herbicide that seriously affects agricultural work and human safety. Melatonin (MLT) as an endogenous neuroendocrine hormone is widely found in animals and plants, which have antioxidant and anti-inflammatory effects. Pink1/Parkin-mediated mitophagy keeps normal physiological processes by degrading damaged mitochondria in cells. Therefore, we investigated the potential role and mechanism of MLT in ATR-induced toxic injury of the spleen. The results showed that MLT alleviated ATR-induced unclear boundary between the white pulp and the red pulp of the spleen. It is also shown that ATR resulted in swollen mitochondria, partial extinction of mitochondrial membranes and cristae, and increased mitophagy under the action of MLT. ATR-induced reactive oxygen species (ROS) activates the Pink1/Parkin pathway, which guides mitophagy development and then causes the activation of TLR4/NF-κB inflammatory pathway. Meanwhile, these damages further exacerbated the production of NLRP3 inflammasomes, leading to spleen necrosis. Interestingly, these changes were improved after MLT treatment. Collectively, we found that MLT alleviates ATR-induced immune impairment in splenic macrophages via regulating Parkin-TLR4-NLRP3 axis which elucidates the effect of melatonin on the spleen and provides a novel perspective on melatonin in splenic inflammatory injury treatment.</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OPA1 Mediated Fatty Acid β-Oxidation in Hepatocyte: The Novel Insight for Melatonin Attenuated Apoptosis in Concanavalin A Induced Acute Liver Injury","authors":"Tong Chen,&nbsp;Ruonan Shuang,&nbsp;Tiantian Gao,&nbsp;Lijun Ai,&nbsp;Jichen Diao,&nbsp;Xinyi Yuan,&nbsp;Ling He,&nbsp;Weiwei Tao,&nbsp;Xin Huang","doi":"10.1111/jpi.70010","DOIUrl":"https://doi.org/10.1111/jpi.70010","url":null,"abstract":"<div>\u0000 \u0000 <p>Melatonin (MLT) has been reported to attenuate Concanavalin A (Con A)-induced acute liver injury via the inhibition of immune cells. Whereas the response of hepatocyte to Con A-caused inflammatory storm and the mechanism of MLT on hepatocyte remain not fully understood. Our RNA-seq and bioinformatic analyses suggested that OPA1 and fatty acid β-oxidation might be critical. It was found that MLT ameliorated Con A-induced acute liver injury, promoted mitochondrial fusion, fatty acid β-oxidation, modulated metabolic reprogramming and inhibited apoptosis. The overexpression and knockdown of OPA1 by adenovirus proved that these processes were governed by OPA1. With the overexpression plasmid, agonist, inhibitor and SiRNA, we found that MLT promoted OPA1 upregulation to enhance fatty acid β-oxidation, which inhibited apoptosis. The MLT and OPA1-promoted fatty acid β-oxidation enhanced ATP production rather than reduced lipid accumulation. AMPK/FOXO1 was required for MLT and OPA1-mediated fatty acid β-oxidation and apoptosis. NOTCH1 was also necessary for this apoptotic process. The results were verified in immune deficiency mice and AML12 cells induced by Con A-stimulated monocyte supernatant. MLT might control the transcription of OPA1 through MEF2A. TOMM70 was critical for MLT translocation and OPA1 upregulation. In conclusion, the present study demonstrated that MLT attenuated Con A-induced acute liver injury via the OPA1-controlled fatty acid β-oxidation to inhibit apoptosis in hepatocyte.</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}