Journal of Pineal Research最新文献

Waterlogging is a major abiotic stress that severely impedes sesame growth and productivity. Melatonin has emerged as a multifaceted regulator in plant stress responses, but its protective mechanisms against waterlogging in sesame, particularly at the proteomic level, remain largely unexplored. A pot experiment was conducted using two sesame genotypes with contrasting waterlogging tolerance (sensitive JHM and tolerant PYH) under well-drained, waterlogging, and waterlogging with melatonin pretreatment conditions. Results showed that waterlogging significantly inhibited plant growth, impaired root architecture, and induced oxidative stress, with more severe impacts on sensitive genotype JHM. Exogenous melatonin application markedly mitigated these adverse effects, reducing the decline in plant height and root growth parameters. Melatonin balanced osmotic pressure by modulating proline and soluble protein content, alleviated oxidative damage by decreasing MDA and H₂O₂ accumulation, and enhanced the activities of SOD, POD, and CAT. It also ameliorated stress signaling by downregulating the accumulation of ABA and ACC, while elevating endogenous melatonin levels. The PYH possessed a superior constitutive antioxidant capacity and hormonal stability, while melatonin was particularly beneficial for JHM. Proteomic analysis identified 1846 differentially expressed proteins (DEPs) in roots of JHM between waterlogged and melatonin-treated plants. These DEPs were predominantly enriched in metabolic pathways, phenylpropanoid biosynthesis, glutathione metabolism, and ROS metabolic processes. MT priming upregulated the expression of superoxide dismutase peroxidase 7, and peroxidase 15-like while downregulated hydrogen peroxide induced protein 1, which were consistent with the results of physiological analysis in JMH. Protein-protein interaction analysis highlighted key proteins like RPL6 and RPL4 as potential hubs within the melatonin-mediated ROS metabolic network. This study provides a comprehensive physiological and molecular elucidation of the multifaceted mechanisms by which melatonin confers waterlogging tolerance, establishing a theoretical foundation for its application in waterlogged regions.

Pepper (Capsicum annuum L. var. cerasiforme Bailey) is highly sensitive to low temperatures, limiting its cultivation in cooler regions. While melatonin (MT) is known to enhance plant cold tolerance through antioxidant and hormonal pathways, its role in modulating cuticular wax composition remains unclear. In this study, we demonstrate that exogenous MT application significantly improves cold resistance in pepper seedlings by upregulating the biosynthesis of long-chain alkanes in epicuticular wax. Physiological assessments revealed that MT treatment (100 μM) increased photosynthetic rate (P_n) by 65.66%, enhanced antioxidant enzyme activities (CAT, POD, SOD), and reduced malondialdehyde (MDA) content by 20.88% after 8 h at 4°C. Transcriptomic and gas chromatography–mass spectrometry (GC–MS) analyses identified two key alkane biosynthesis genes, CaCER1-like and CaCER1-like1. The expression of CaCER1-like was specifically induced by exogenous melatonin, while CaCER1-like1 was primarily upregulated by low-temperature stress. This coordinated transcriptional activation enhanced the accumulation of C27, C29, and C31 alkanes. Beyond cold-induced alkane biosynthesis, melatonin treatment provided a further 25.5% increase in total alkane content (MT8 vs. CK8), with a marked 27.5% rise in the critical C31 alkane. These compounds constituted over 57.7% of the wax. Scanning electron microscopy (SEM) imaging further showed that MT-induced wax crystallization shifted from lamellar to aggregated structures, with a reduction in epidermal gaps, suggesting a potential reduction in nonstomatal water loss. These findings reveal a novel mechanism by which melatonin enhances cold tolerance via wax modification, providing a potential strategy for improving pepper cultivation in cold climates.

Litchi (Litchi chinensis Sonn.) is a non-climacteric fruit with a red pericarp that browns after harvest, reducing market value. Pericarp browning is linked to oxidative stress caused by reactive oxygen species (ROS). This study explored the combined effects of ultrasound (US; 37 ± 3 kHz for 10 min) and melatonin (1 and 2 mM) on litchi pericarp browning during ambient storage. On last day of storage, US combined with 1 and 2 mM melatonin exhibited lowest pericarp browning compared to their individual application with a score of 2.54 and 3.64. The results suggest that, combined treatment of ultrasound and melatonin effectively mitigates oxidative stress with lower ROS accumulation and polyphenol oxidase activity. Additionally, higher levels of anthocyanins, polyphenols, antioxidants, and phenylalanine ammonia lyase activity were maintained. It also preserved fruit quality, including weight, soluble solids, and titratable acidity, while reducing decay suggesting combined treatment of ultrasound and melatonin effectively enhances the postharvest quality of litchi fruit with reduced pericarp browning

The cAMP response element-binding protein (CREB) and Period1 (Per1) have been implicated in depression, but their interactive mechanisms remain unclear. This study investigated the integrative role of CREB and Per1 in depression and explores a potential strategy for rapid antidepressant treatment. Using a chronic unpredictable stress (CUS) model, we conducted behavioral assessments including the sucrose preference test, forced swimming test, elevated plus maze, and open field test. Gene expression was manipulated via stereotaxic surgery and RNA interference (RNAi), while protein levels and viral injection sites were verified through Western blot analysis and immunofluorescence. Additionally, we generated Per1 CRE knockout rats using CRISPR/Cas9, with genotypes confirmed by Sanger sequencing. CUS significantly reduced phosphorylated CREB (pCREB) and PER1 levels in the CA1 region. Both Per1 knockdown in CA1 and CRE sequence knockout induced depression-like behaviors, whereas Per2 knockdown in CA1 produced mania-like behaviors. Notably, CRE knockout in the Per1 promoter increased pCREB binding to the Per2 promoter, upregulating PER2 expression in the CA1 and resulting in depression-like phenotypes that are partially lithium-responsive. Treatment with the adenosine A₁ receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA) elevated pCREB and PER1 levels in the CA1 and elicited rapid antidepressant effects. These effects were present in heterozygotes but absent in homozygotes with a mutated Per1 CRE sequence. These results revealed the pivotal role of the pCREB-CRE-Per1 pathway in CUS-induced depression and its mediation of rapid antidepressant-like effects via adenosine A₁ receptor activation. Moreover, the CRE sequence in the Per1 promoter may be a critical molecular link to the pathophysiology of bipolar depression.

The treatment of prostate cancer (PCa) remains challenging, and while melatonin (MEL) has demonstrated therapeutic potential, its precise mechanisms require further elucidation. Through integrated in vitro, in vivo, and bioinformatics analyses, this study demonstrated that MEL functioned as a novel ferroptosis inducer in PCa by disrupting androgen receptor (AR) liquid-liquid phase separation (LLPS). We found that MEL effectively inhibited PCa proliferation, migration, and invasion in vitro while suppressing tumor growth safely in mice models. Mechanistically, MEL impaired AR LLPS dynamics, reducing AR-driven transcription of minichromosome maintenance protein 5 (MCM5). MCM5 was a clinically relevant biomarker associated with aggressive PCa and poor survival. Crucially, downregulated MCM5 attenuated its physical interaction with NRF2, leading to uncontrolled activation of the NRF2/HMOX1 pathway, GPX4 suppression, and accumulation of ferroptosis hallmarks. These findings defined an AR/MCM5/NRF2 axis regulating ferroptosis susceptibility, establishing MEL as the first-reported ferroptosis inducer that expands the mechanistic foundation and therapeutic potential of MEL-based PCa treatment strategies.

Systemic lupus erythematosus (SLE) is an autoimmune disorder featuring abnormal B cell differentiation and excessive autoantibody production, leading to multiorgan damage. Despite advances in understanding SLE pathogenesis, the molecular mechanisms driving aberrant B cell differentiation remain elusive. Melatonin, a neuroendocrine hormone with immunomodulatory properties, has been shown to regulate immune responses, but its role in B cell differentiation and SLE is poorly understood. This study investigates the role of melatonin and its receptors in B cell differentiation and SLE pathogenesis. We observed reduced serum melatonin levels and decreased expression of melatonin receptors in B cells from SLE patients and MRL/Lpr mice. Activation of melatonin receptors inhibited the protein kinase A (PKA) signaling pathway and reduced phosphorylation of cyclic-AMP response binding protein (CREB), leading to epigenetic downregulation of PRDM1 and IRF4, key transcription factors for plasmablast and plasma cell differentiation. Consequently, melatonin receptor activation suppressed abnormal B cell differentiation into antibody-secreting cells. Our findings highlight melatonin and its receptor signaling as potential therapeutic targets for SLE and other autoimmune diseases mediated by aberrant antibody-secreting cell activity. This study provides novel insights into the protective role of melatonin in SLE and offers a promising avenue for developing targeted therapies.

Melatonin (MT) plays a critical role in regulating rice responses to heavy metal stress. However, the mechanism by which MT alleviates copper (Cu) toxicity in rice remains insufficiently understood. In this study, excessive Cu increased endogenous MT level in rice roots, accompanied by enhanced gene expression involved in MT biosynthesis, suggesting its role in Cu stress responses. Exogenous MT reduced Cu accumulation and restored root growth in rice under Cu stress, thereby mitigating Cu-induced phytotoxicity. Mechanistically, MT increased the root pectin content and its Cu retention, thereby reducing Cu influx into the cytoplasm. Additionally, exogenous MT upregulated the expression of Heavy Metal ATPase 4 (OsHMA4) involved in vacuolar sequestration, as well as Cu efflux transporter genes OsHMA6 and OsHMA9. Conversely, it downregulated the plasma membrane Cu uptake-associated genes Copper Transporter (OsCOPT1, OsCOPT2, and OsCOPT3), the vacuolar Cu exporter OsCOPT7, and the xylem loading transporter gene OsHMA5, thereby alleviating Cu toxicity in rice. Furthermore, MT elevated nitric oxide (NO) levels in root tips, and application of the exogenous NO scavenger, 2-(4-carboxyphenyl)−4, 4, 5, 5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO), attenuated the mitigative effect of MT on excess Cu-stressed rice. In summary, MT alleviates Cu toxicity by reducing Cu binding to root cell walls, thereby limiting Cu uptake and translocation from roots to shoots. This process may depend on NO accumulation and provides new insights into the molecular mechanisms underlying MT-induced Cu tolerance in rice.

Soil contamination by microplastics (MPs) and heavy metals has become a global ecological and environmental issue and poses considerable threats to crop production and human health. In plants, melatonin (MT) functions as a powerful biostimulant, orchestrating vital physiological processes and enhancing stress tolerance. In this study, through controlled pot experiments, how exogenous MT (0.1 mmol L⁻¹) modulates maize responses to low-density polyethylene (LDPE) MPs, cadmium (Cd), and their combination was investigated. Simultaneous exposure to LDPE MPs and Cd exacerbated oxidative damage, inhibited chlorophyll biosynthesis, suppressed photosynthetic capacity, and reduced biomass in maize plants, alongside increasing shoot and root Cd²⁺ levels. Conversely, exogenous MT application reduced the malondialdehyde content by 12.5% under combined stress conditions, indicating a substantial reduction in oxidative damage. Additionally, MT inhibited the absorption and accumulation of Cd²⁺, increased the chlorophyll content, enhanced the photosynthetic efficiency, improved the plant height and stem diameter, thereby increasing maize plant biomass by 5.6%. MT also increased the activity of reactive oxygen species scavenging antioxidant enzymes and promoted the biosynthesis of non-enzymatic antioxidants such as proline and soluble sugars. Metabolomic analysis revealed that exogenous MT treatment significantly affected the levels of 210 metabolites. Notably, key metabolic pathways, including purine metabolism, phenylpropanoid biosynthesis, and tryptophan metabolism, were upregulated, indicating their pivotal role in the stress response mechanism of plants. These results reveal that exogenous MT effectively alleviates the synergistic phytotoxicity of PE MPs and Cd in maize plants, underscoring its promise as a practical strategy for enhancing crop resilience in contaminated environments.