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1.
Cells ; 12(2)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36672220

RESUMO

The pineal gland is integral to the circadian timing system due to its role in nightly melatonin production. Retinoic acid (RA) is a potent regulator of gene transcription and has previously been found to exhibit diurnal changes in synthesis and signalling in the rat pineal gland. This study investigated the potential for the interaction of these two systems. PCR was used to study gene expression in mouse and human pineal glands, ex-vivo organotypic cultured rat pineal gland and cell lines. The mouse and human pineal glands were both found to express the necessary components required for RA signalling. RA influences the circadian clock in the brain, therefore the short-term effect of RA on clock gene expression was determined in ex vivo rat pineal glands but was not found to rapidly regulate Per1, Per2, Bmal1, or Cry1. The interaction between RA and melatonin was also investigated and, unexpectedly, melatonin was found to suppress the induction of gene transcription by RA. This study demonstrates that pineal expression of the RA signalling system is conserved across mammalian species. There is no short-term regulation of the circadian clock but an inhibitory effect of melatonin on RA transcriptional activity was demonstrated, suggesting that there may be functional cross-talk between these systems.


Assuntos
Melatonina , Glândula Pineal , Ratos , Camundongos , Humanos , Animais , Glândula Pineal/metabolismo , Melatonina/farmacologia , Melatonina/metabolismo , Tretinoína/farmacologia , Tretinoína/metabolismo , Transdução de Sinais , Mamíferos/metabolismo
2.
Int J Mol Sci ; 24(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36614184

RESUMO

Fine-tuned interactions between melatonin (MT) and hormones affected by environmental inputs are crucial for plant growth. Under high light (HL) conditions, melatonin reduced photodamage in Arabidopsis thaliana and contributed to the restoration of the expression of the cytokinin (CK) synthesis genes IPT3, IPT5 and LOG7 and genes for CK signal transduction AHK2,3 and ARR 1, 4, 5 and 12 which were downregulated by stress. However, CK signaling mutants displayed no significant changes in the expression of CK genes following HL + MT treatment, implying that a fully functional cytokinin signaling pathway is a prerequisite for MT-CK interactions. In turn, cytokinin treatment increased the expression of the key melatonin synthesis gene ASMT under both moderate and HL in wild-type plants. This upregulation was further accentuated in the ipt3,5,7 mutant which is highly sensitive to CK. In this mutant, in addition to ASMT, the melatonin synthesis genes SNAT and COMT, as well as the putative signaling genes CAND2 and GPA1, displayed elevated transcript levels. The results of the study suggest that melatonin acts synergistically with CK to cope with HL stress through melatonin-associated activation or repression of the respective hormonal genes.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Melatonina , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Citocininas/farmacologia , Citocininas/metabolismo , Regulação da Expressão Gênica de Plantas , Subunidades alfa de Proteínas de Ligação ao GTP/metabolismo , Melatonina/farmacologia , Melatonina/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais/genética , Estresse Fisiológico
3.
Int J Mol Sci ; 24(2)2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36674694

RESUMO

Melatonin (MT) is a new plant hormone that protects against adverse environmental conditions. In the present study, the responses of Wolffia arrhiza exposed to cadmium (Cd) and MT were analyzed. Quantitative analysis of MT and precursors of its biosynthesis was performed using LC-MS-MS. The photosynthetic pigments and phytochelatins (PCs) contents were determined using HPLC, while protein and monosaccharides, stress markers, and antioxidant levels were determined using spectrophotometric methods. Interestingly, the endogenous level of MT and its substrates in W. arrhiza exposed to 1-100 µM Cd was significantly higher compared to the control. Additionally, the application of 25 µM MT and Cd intensified the biosynthesis of these compounds. The most stimulatory effect on the growth and content of pigments, protein, and sugars was observed in plants treated with 25 µM MT. In contrast, Cd treatment caused a decrease in plant weight and level of these compounds, while the application of 25 µM MT mitigated the inhibitory effect of Cd. Additionally, Cd enhanced the level of stress markers; simultaneously, MT reduced their content in duckweed exposed to Cd. In plants treated with Cd, PC levels were increased by Cd treatment and by 25 µM MT. These results confirmed that MT mitigated the adverse effect of Cd. Furthermore, MT presence was reported for the first time in W. arrhiza. In summary, MT is an essential phytohormone for plant growth and development, especially during heavy metal stress.


Assuntos
Araceae , Melatonina , Melatonina/farmacologia , Melatonina/metabolismo , Cádmio/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Estresse Oxidativo , Reguladores de Crescimento de Plantas/metabolismo
4.
J Agric Food Chem ; 71(3): 1748-1757, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36647270

RESUMO

Spirodela polyrhiza (Araceae family) is a duckweed species that serves as a potential resource for feed, food, bioremediation, and pharmaceutical applications. In this study, we assessed the effects of different concentrations of melatonin (0, 0.1, 1, and 10 µM) on the growth of S. polyrhiza during in vitro culture and the metabolic profiles and productivities of useful metabolites using gas chromatography-mass spectrometry coupled with multivariable statistical analysis. We found that exogenous melatonin significantly improved the total dry weight and altered the metabolic profiles of S. polyrhiza cultures. Melatonin significantly enhanced the cellular production of useful metabolites, such as γ-aminobutyric acid, dopamine, threonine, valine, and phytosterols. The volumetric productivities (mg/L) of γ-aminobutyric acid, dopamine, campesterol, ß-sitosterol, and stigmasterol were the highest in the presence of 10 µM melatonin on day 12. Moreover, the productivities of ascorbic acid and serotonin were the highest in the presence of 1 µM melatonin on day 12. Therefore, melatonin could be used to enhance the production of biomass and useful metabolites during large-scale S. polyrhiza cultivation in cosmetic, food/feed, and pharmaceutical industries.


Assuntos
Araceae , Melatonina , Melatonina/farmacologia , Melatonina/metabolismo , Dopamina/metabolismo , Araceae/metabolismo , Biodegradação Ambiental , Ácido gama-Aminobutírico/metabolismo
5.
FASEB J ; 37(2): e22784, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36692416

RESUMO

Hypoxia-ischemia (HI) is a major cause of brain damage in neonates. Mitochondrial dysfunction acts as a hub for a broad spectrum of signaling events, culminating in cell death triggered by HI. A neuroprotective role of melatonin (MT) has been proposed, and mitophagy regulation seems to be important for cell survival. However, the molecular mechanisms underlying MT-mediated mitophagy during HI treatment are poorly defined. Nucleotide-binding oligomerization domain and leucine-rich repeat-containing protein X1 (NLRX1) has emerged as a critical regulator of mitochondrial dynamics and neuronal death that participates in the pathology of diverse diseases. This study aimed to clarify whether NLRX1 participates in the regulation of mitophagy during MT treatment for hypoxic-ischemic brain damage (HIBD). We demonstrated that MT protected neonates from HIBD through NLRX1-mediated mitophagy in vitro and in vivo. Meanwhile, MT upregulated the expression of NLRX1, Beclin-1, and autophagy-related 7 (ATG7) but decreased the expression of the mammalian target of rapamycin (mTOR) and translocase of the inner membrane of mitochondrion 23 (TIM23). Moreover, the neuroprotective effects of MT were abolished by silencing NLRX1 after oxygen-glucose deprivation (OGD). In addition, the downregulation of mTOR and upregulation of Beclin-1 and ATG7 by MT were inhibited after silencing NLRX1 under OGD. In summary, MT modulates mitophagy induction through NLRX1 and plays a protective role in HIBD, providing insight into potential therapeutic targets for MT to exert neuroprotection.


Assuntos
Hipóxia-Isquemia Encefálica , Melatonina , Fármacos Neuroprotetores , Humanos , Recém-Nascido , Mitofagia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Leucina/farmacologia , Melatonina/farmacologia , Proteína Beclina-1/metabolismo , Hipóxia-Isquemia Encefálica/metabolismo , Hipóxia/tratamento farmacológico , Oxigênio/farmacologia , Glucose/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Nucleotídeos , Encéfalo/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo
6.
Viruses ; 15(1)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36680196

RESUMO

Aging processes, including immunosenescence, inflammation, inflammasome formation, genomic instability, telomeric attrition, and altered autophagy, are involved in viral infections and they may contribute to increased pathophysiological responses to the SARS-CoV-2 infection in the elderly; this poses additional risks of accelerated aging, which could be found even after recovery. Aging is associated with oxidative damage. Moreover, SARS-CoV-2 infections may increase the production of reactive oxygen species and such infections will disturb the Ca++ balance via an endoplasmic reticulum (ER) stress-mediated unfolded protein response. Although vaccine development and anti-inflammation therapy lower the severity of COVID-19, the prevalence and mortality rates are still alarming in some countries worldwide. In this review, we describe the involvement of viral proteins in activating ER stress transducers and their downstream signals and in inducing inflammation and inflammasome formation. Furthermore, we propose the potential of melatonin as an ER stress modulator, owing to its antioxidant, anti-inflammatory, and immunoregulatory effects in viral infections. Considering its strong safety profile, we suggest that additive melatonin supplementation in the elderly could be beneficial in treating COVID-19.


Assuntos
COVID-19 , Melatonina , Humanos , Idoso , Melatonina/uso terapêutico , Melatonina/farmacologia , Inflamassomos , SARS-CoV-2/metabolismo , Estresse do Retículo Endoplasmático
7.
PeerJ ; 11: e14612, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36684672

RESUMO

Background: Communication between oocytes and granulosa cells ultimately dictate follicle development or atresia. Melatonin is also involved in follicle development. This study aimed to investigate the effects of melatonin and its receptor antagonists on hormone secretion, as well as gene expression related to hormone synthesis, TGF-ß superfamily, and follicle development in bovine granulosa cells, and assess the effects of melatonin in the presence of 4-P-PDOT and luzindole. Methods: Bovine ovaries were collected from a local abattoir and follicular fluid (follicle diameter 5-8 mm) was collected for granulosa cell isolation and culture. Granulosa cells and culture medium were collected 48 h after treatment with melatonin at high dose concentrations (10-5 M) and low dose concentrations (10-9 M) in the absence/presence of 4-P-PDOT and luzindole (10-5 M or 10-9 M). Furthermore, the expression level of genes related to hormonal synthesis (CYP11A1, CYP19A1, StAR, and RUNX2), TGF-ß superfamily (BMP6, INHA, INHBA, INHBB, and TGFBR3), and development (EGFR, DNMT1A, and FSHR) were detected in each experimental group by real-time quantitative PCR. In addition, the level of hormones in culture medium were detected using ELISA. Results: Both 10-5 M and 10-9 M melatonin doses promoted the secretion of inhibin A and progesterone without affecting the production of inhibin B and estradiol. In addition, both promoted the gene expression of INHA, StAR, RUNX2, TGFBR3, EGFR, and DNMT1A, and inhibited the expression of BMP6, INHBB, CYP11A1, CYP19A1, and FSHR. When combined with different doses of 4-P-PDOT and luzindole, they exhibited different effects on the secretion of inhibin B, estradiol, inhibin A, and progesterone, and the expression of CYP19A1, RUNX2, BMP6, INHBB, EGFR, and DNMT1A induced by melatonin. Conclusion: High and low dose melatonin receptor antagonists exhibited different effects in regulating hormone secretion and the expression of various genes in response to melatonin. Therefore, concentration effects must be considered when using luzindole or 4-P-PDOT.


Assuntos
Melatonina , Feminino , Animais , Bovinos , Melatonina/farmacologia , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Progesterona/metabolismo , Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Células da Granulosa , Estradiol/metabolismo , Receptores ErbB/metabolismo
8.
Sci Rep ; 13(1): 1196, 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36681714

RESUMO

Calmodulin-like proteins (CML) are important calcium signal transduction proteins in plants. CML genes have been analyzed in several plants. However, little information on CML in Phaseolus vulgare is available. In this study, we identified 111 PvCMLs distributed on eleven chromosomes. Phylogenetic analysis classified them into seven subfamilies. Cis-acting element prediction showed that PvCML contained elements related to growth and development, response to abiotic stress and hormones. Moreover, the majority of PvCMLs showed different expression patterns in most of the nine tissues and developmental stages which indicated the role of PvCML in the growth and development of common bean. Additionally, the common bean was treated with melatonin by seed soaking, and root transcriptome at the 5th day and qRT-PCR of different tissue at several stages were performed to reveal the response of PvCML to the hormone. Interestingly, 9 PvCML genes of subfamily VI were detected responsive to exogenous melatonin, and the expression dynamics of nine melatonin response PvCML genes after seed soaking with melatonin were revealed. Finally, the protein interaction network analysis of nine melatonin responsive PvCMLs was constructed. The systematic analysis of the PvCML gene family provides theoretical support for the further elucidation of their functions, and melatonin response molecular mechanism of the CML family in P. vulgaris.


Assuntos
Melatonina , Phaseolus , Phaseolus/metabolismo , Melatonina/farmacologia , Melatonina/metabolismo , Filogenia , Transcriptoma , Estresse Fisiológico/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas
9.
Theriogenology ; 198: 172-182, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36592515

RESUMO

Theca cells (TCs) play a unique role in the structure and function of the ovary. They are not only the structural basis of the follicle but also the androgen-secreting cells in female mammals, which can affect the normal development and atresia of the follicle. The results showed that melatonin receptor (MTR) MT1 and MT2 were expressed on sheep TCs. In the present study, the effects of different concentrations of MT at 0, 10-10, 10-8, 10-6 and 10-4 M/L on sheep TCs with regards to the antioxidant levels, proliferation, apoptosis and steroid hormone secretion were investigated. The results showed that in sheep TCs, all concentrations of MT significantly decreased reactive oxygen species (ROS) concentration and BAX expression; increased Cat, Sod1, and BCL-2 expression. The proliferation viability of TCs was significantly inhibited in all groups except for 10-10 M/L MT, and the expression of cyclin D1 and CDK4 was significantly reduced. MT significantly increased StAR expression and progesterone secretion in TCs, but there was no significant effect on androgen secretion and CYP11A1, CYP17A1 and 3ß-HSD expression in all groups. MT-induced progesterone secretion was completely inhibited by Luzindole (a nonspecific MT1 and MT2 inhibitor) and partially inhibited by 4p-PDOT (specific MT2 inhibitor). MT-induced progesterone secretion can be inhibited by LY294002 (PI3K/AKT pathway inhibitor). This study indicated that MT inhibits apoptosis and proliferation of in vitro cultured sheep TCs, which has implications for slowing ovarian atresia and aging. MT activates the PI3K/Akt pathway to mediate the synthesis and secretion of progesterone by TCs. This study provides a basis for further exploration of the role of TCs on follicle development and ovarian steroid hormone secretion.


Assuntos
Melatonina , Feminino , Animais , Ovinos , Melatonina/farmacologia , Células Tecais , Progesterona/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Androgênios/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Receptor MT2 de Melatonina/metabolismo , Mamíferos
10.
ACS Appl Mater Interfaces ; 15(2): 2639-2655, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36603840

RESUMO

At present, surgery is one of the main treatments for bone tumor. However, the risk of recurrence and the large area of bone defects after surgery pose a great challenge. Therefore, a Janus-inspired core-shell structure bone scaffold was designed to achieve the self-programmed release of melatonin at different concentrations, clearing the residual tumor cells at early stage after resection and promoting bone repair later. The layered differential load designs inspired by Janus laid the foundation for the differential release of melatonin, where sufficient melatonin inhibited tumor growth as low dose promoted osteogenesis. Then, the automatically programmed delivery of melatonin is achieved by the gradient degradation of the core-shell structure. In the material characterization, scanning electron microscopy revealed the core-shell structure. The drug release experiment and in vivo degradation experiment reflected the programmed differential release of melatonin. In the biological experiment part, in vivo and in vitro experiments not only confirmed the significant inhibitory effect of the core-shell hydrogel scaffold on tumor but also confirmed its positive effect on osteogenesis. Our Janus-inspired core-shell hydrogel scaffold provides a safe and efficient means to inhibit tumor recurrence and bone repair after bone tumor, and it also develops a new and efficient tool for differential and programmed release of other drugs.


Assuntos
Neoplasias Ósseas , Melatonina , Humanos , Hidrogéis/química , Tecidos Suporte/química , Melatonina/farmacologia , Osteogênese , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/cirurgia , Regeneração Óssea
11.
Int J Mol Sci ; 24(2)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36674472

RESUMO

Increased adiposity is related to oxidative stress, inflammation and metabolic disorders. Our group has shown that melatonin totally or partially prevents the alterations that obesity causes in some neuroendocrine and inflammatory parameters indicative of oxidative stress. This study analyzes the effects of HFD on the relative gene expression of several redox balance enzymes on adult male Wistar rats subcutaneous (SAT) and perirenal adipose tissue (PRAT) and the possible preventive role of melatonin. Three experimental groups were established: control, high fat diet (HFD) and HFD plus 25 µg/mL melatonin in tap water. After 11 weeks, animals were sacrificed at 09:00 a.m. and 01:00 a.m. and PRAT and SAT were collected for selected redox enzymes qRT-PCR. Differential expression of redox enzyme genes, except for SODMn, GPx and catalase, was observed in the control group as a function of fat depot. HFD causes the disappearance of the temporal changes in the expression of the genes studied in the two fat depots analyzed. PRAT seems to be more sensitive than SAT to increased oxidative stress induced by obesity. Melatonin combined with a HFD intake, partially prevents the effects of the HFD on the gene expression of the redox enzymes. According to our results, melatonin selectively prevents changes in the relative gene expression of redox enzymes in PRAT and SAT of animals fed an HFD.


Assuntos
Melatonina , Ratos , Animais , Masculino , Melatonina/farmacologia , Melatonina/metabolismo , Ratos Wistar , Obesidade/genética , Obesidade/metabolismo , Gordura Subcutânea/metabolismo , Tecido Adiposo/metabolismo , Dieta Hiperlipídica/efeitos adversos , Oxirredução , Expressão Gênica
12.
Int J Mol Sci ; 24(2)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36674787

RESUMO

Prenatal stress impairs cognitive function in rats, while Piromelatine treatment corrects memory decline in male rats with chronic mild stress. In the present study, we aimed to evaluate the effect of chronic treatment with the melatonin analogue Piromelatine on the associative and spatial hippocampus-dependent memory of male and female offspring with a history of prenatal stress (PNS). We report that male and female young adult offspring with PNS treated with a vehicle had reduced memory responses in an object recognition test (ORT). However, the cognitive performance in the radial arm maze test (RAM) was worsened only in the male offspring. The 32-day treatment with Piromelatine (20 mg/kg, i.p.) of male and female offspring with PNS attenuated the impaired responses in the ORT task. Furthermore, the melatonin analogue corrected the disturbed spatial memory in the male offspring. While the ratio of phosphorylated and nonphosphorylated adenosine monophosphate response element binding protein (pCREB/CREB) was reduced in the two sexes with PNS and treated with a vehicle, the melatonin analogue elevated the ratio of these signaling molecules in the hippocampus of the male rats only. Our results suggest that Piromelatine exerts a beneficial effect on PNS-induced spatial memory impairment in a sex-dependent manner that might be mediated via the pCREB/CREB pathway.


Assuntos
Melatonina , Gravidez , Ratos , Masculino , Feminino , Animais , Melatonina/farmacologia , Transtornos da Memória/etiologia , Transtornos da Memória/induzido quimicamente , Transdução de Sinais , Indóis/farmacologia , Aprendizagem em Labirinto , Hipocampo/metabolismo
13.
Int J Mol Sci ; 24(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36614180

RESUMO

Melatonin (MT) is a phytohormone-like substance and is profoundly involved in modulating nearly all aspects of plant development and acclimation to environmental stressors. However, there remain no studies about the effects of MT on tomato seed germination under salt stress. Here we reported that the overexpression of caffeic acid O-methyltransferase 1 (SlCOMT1) significantly increased both MT content and salt tolerance in the germinated seeds of a transgenic tomato relative to wild type (WT) samples. Physiological investigation showed higher amylase activity in the stressed overexpression seeds than WT, leading to the promoted starch decomposition and enhanced soluble sugar content. The stimulated production of osmolytes and enhanced activities of SOD, POD, and CAT, together with the significant reduction in H2O2 and O2·- accumulation, were revealed in the stressed overexpression seeds relative to WT, largely accounting for their lower membrane lipid peroxidation. qPCR assay showed that, upon salt stress, the transcript abundance of hub genes related to germination (SlCYP707A1, SlABA1, SlGA3ox2 and SlGA2ox4) and stress tolerance (SlCDPK1, SlWRKY33 and SlMAPK1) were distinctly altered in the overexpression samples when compared to WT, providing a molecular basis for MT-mediated improvement of seed salt tolerance. Altogether, our observations shed new insights into biological functions of SlCOMT1 and could expand its utilization in genetic improvement of tomato salt tolerance in future.


Assuntos
Melatonina , Germinação/genética , Peróxido de Hidrogênio/metabolismo , Sementes , Estresse Salino/genética , Melatonina/farmacologia , Regulação da Expressão Gênica de Plantas , Estresse Fisiológico
14.
Med Sci (Basel) ; 11(1)2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36649046

RESUMO

Melanoma is the most aggressive type of skin cancer, with a greater risk of metastasis and a higher prevalence and mortality rate. This cancer type has been demonstrated to develop resistance to the known treatment options such as conventional therapeutic agents and targeted therapy that are currently being used as the standard of care. Drug repurposing has been explored as a potential alternative treatment strategy against disease pathophysiologies, including melanoma. To that end, multiple studies have suggested that melatonin produced by the pineal gland possesses anti-proliferative and oncostatic effects in experimental melanoma models. The anticarcinogenic activity of melatonin is attributed to its ability to target a variety of oncogenic signaling pathways, including the MAPK pathways which are involved in regulating the behavior of cancer cells, including cell survival and proliferation. Additionally, preclinical studies have demonstrated that melatonin in combination with chemotherapeutic agents exerts synergistic effects against melanoma. The goal of this review is to highlight the mechanistic insights of melatonin as a monotherapy or combinational therapy for melanoma treatment.


Assuntos
Melanoma Experimental , Melatonina , Glândula Pineal , Neoplasias Cutâneas , Animais , Melatonina/uso terapêutico , Melatonina/farmacologia , Neoplasias Cutâneas/tratamento farmacológico , Melanoma Experimental/tratamento farmacológico , Transdução de Sinais
15.
J Proteomics ; 273: 104791, 2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36538967

RESUMO

Cryopreservation may reduce sperm fertility due to cryodamage including physical-chemical and oxidative stress damages. As a powerful antioxidant, melatonin has been reported to improve cryoprotective effect of sperm. However, the molecular mechanism of melatonin on cryopreserved ram sperm hasn't been fully understand. Give this, this study aimed to investigate the postthaw motility parameters, antioxidative enzyme activities and lipid peroxidation, as well as proteomic, metabolomic changes of Huang-huai ram spermatozoa with freezing medium supplemented with melatonin. Melatonin was firstly replenished to the medium to yield five different final concentrations: 0.1, 0.5, 1.0, 1.5, and 2.0 mM. A control (NC) group without melatonin replenishment was included. Protective effects of melatonin as evidenced by postthaw motility, activities of T-AOC, T-SOD, GSH-Px, CAT, contents of MDA, 4-HNE, as well as acrosome integrity, plasma membrane integrity, with 0.5 mM being the most effective concentration (MC group). Furthermore, 29 differentially abundant proteins involving in sperm functions were screened among Fresh, NC and MC groups of samples (n = 5) based on the 4D-LFQ, with 7 of them upregulated in Fresh and MC groups. 26 differentially abundant metabolites were obtained involving in sperm metabolism among the three groups of samples (n = 8) based on the UHPLC-QE-MS, with 18 of them upregulated in Fresh and MC groups. According to the bioinformatic analysis, melatonin may have positive effects on frozen ram spermatozoa by regulating the abundance changes of vital proteins and metabolites related to sperm function. Particularly, several proteins such as PRCP, NDUFB8, NDUFB9, SDHC, DCTN1, TUBB6, TUBA3E, SSNA1, as well as metabolites like L-histidine, L-targinine, ursolic acid, xanthine may be potential novel biomarkers for evaluating the postthaw quality of ram spermatozoa. In conclusion, a dose-dependent replenishment of melatonin to freezing medium protected ram spermatozoa during cryopreservation, which can improve motility, antioxidant enzyme activities, reduce levels of lipid peroxidation products, modify the proteomic and metabolomic profiling of cryopreserved ram spermatozoa through reduction of oxidative stress, maintenance of OXPHOS and microtubule structure. SIGNIFICANCE: Melatonin, a powerful antioxidant protects ram spermatozoa from cryopreservation injuries in a dose-dependent manner, with 0.5 mM being the most effective concentration. Furthermore, sequencing results based on the 4D-LFQ combined with the UHPLC-QE-MS indicated that melatonin modifies proteomic and metabolomic profiling of ram sperm during cryopreservation. According to the bioinformatic analysis, melatonin may have positive effects on frozen ram spermatozoa by regulating the expression changes of vital proteins and metabolites related to sperm metabolism and function. Particularly, several potential novel biomarkers for evaluating the postthaw quality of ram spermatozoa were acquired, proteins such as PRCP, NDUFB8, NDUFB9, SDHC, DCTN1, TUBB6, TUBA3E, SSNA1, as well as metabolites like L-histidine, L-targinine, ursolic acid, xanthine.


Assuntos
Melatonina , Preservação do Sêmen , Animais , Masculino , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Criopreservação/métodos , Histidina/metabolismo , Histidina/farmacologia , Melatonina/farmacologia , Melatonina/metabolismo , Proteômica , Sêmen , Preservação do Sêmen/métodos , Ovinos , Motilidade Espermática , Espermatozoides/metabolismo , Xantinas/metabolismo , Xantinas/farmacologia , Metabolômica
16.
Environ Pollut ; 319: 120973, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36584859

RESUMO

Bioremediation with photosynthetic bacteria (PSB) is thought to be a promising removal method for hexavalent chromium [Cr(VI)]-containing wastewater. In the present study, Rhodobacter sphaeroides (R. sphaeroides) SC01 was used for the investigation of Cr(VI) removal in Cr(VI)-contaminated solution in the presence of melatonin. It was found that exogenous melatonin alleviated oxidative damage to R. sphaeroides SC01, increased Cr (VI) absorption capacity of cell membrane, and improved the reduction efficiency of Cr(VI) via the activation of chromate reductants. The results showed that melatonin could further promote the increase in Cr(VI) removal efficiency, reaching up to 97.8%. Furthermore, melatonin application resulted in 296.9%, 44.4%, and 69.7% upregulation of ascorbic acid (AsA), glutathione (GSH), and cysteine (Cys) relative to non-melatioin treated R. sphaeroides SC01 at 48 h. In addition, the resting cells, cell-free supernatants (CFS), and cell-free extracts (CFE) with melatonin had a higher Cr(VI) removal rate of 18.6%, 82.0%, and 15.2% compared with non-melatonin treated R. sphaeroides SC01. Fourier transform infrared spectroscopy (FTIR) revealed that melatonin increased the binding of Cr(III) with PO43- and CO groups on cell membrane of R. sphaeroides SC01. X-ray diffractometer (XRD) analysis demonstrated that melatonin remarkably bioprecipitated the production of CrPO4·6H2O in R. sphaeroides SC01. Hence, these results indicated that melatonin plays the important role in the reduction and uptake of Cr(VI), demonstrating it is a great promising strategy for the management of Cr(VI) contaminated wastewater in photosynthetic bacteria.


Assuntos
Melatonina , Rhodobacter sphaeroides , Poluentes Químicos da Água , Rhodobacter sphaeroides/metabolismo , Antioxidantes , Melatonina/farmacologia , Cromo/química , Adsorção , Poluentes Químicos da Água/análise
17.
Theriogenology ; 198: 36-46, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36542876

RESUMO

Sperm orientation mechanisms, such as chemotaxis, are essential for the sperm to reach the oocyte and fertilize it. Melatonin is secreted by the cumulus cells and is also present in the follicular fluid in mammals. The presence of membrane receptors for melatonin in ram spermatozoa, and its proven involvement in the sperm functionality, may suggest a possible role in the guided movement towards the oocyte. Hence, the objective of the present work is to study the in vitro potential chemotactic action of melatonin on ram spermatozoa, analysing the influence of the season (breeding and non-breeding) and the sperm capacitation state. The first experimental approach consisted in the inclusion of melatonin in the upper layer of a swim-up selection method. During the non-breeding season, the presence of melatonin at 100 pM and 1 µM concentrations significantly increased the cell recovery rate, and induced changes in the sperm location of the MT2 melatonin receptor, compared with the standard swim-up. Moreover, the selected sperm population with 100 pM melatonin presented a higher percentage of capacitated spermatozoa. The greater recovery rate obtained with melatonin could be due to the stimulation of sperm movement in random directions, i.e., a chemokinetic effect, or due to a guided movement (chemotaxis) towards the gradient of the melatonin. To elucidate this issue, together with the study of the influence of the sperm capacitation status, we performed a second experimental approach which consisted in the use of chemotaxis chambers and an open-source software (Open-CASA) that analyses the sperm trajectories towards the hormone gradient and calculates a chemotaxis index (SL index). There was a significant difference between the SL index in the presence of 1 µM melatonin and the control without hormone. This effect was only observed in capacitated spermatozoa with cAMP-elevating agents (Cap-CK samples) obtained during the non-breeding season. These results would point to an in vitro chemotactic effect of melatonin on ram spermatozoa, although chemokinesis cannot be ruled out. Nonetheless, the inclusion of this hormone in the swim-up procedure could enhance the sperm recovery rate.


Assuntos
Melatonina , Feminino , Masculino , Ovinos , Animais , Melatonina/farmacologia , Sêmen , Espermatozoides/fisiologia , Fertilização , Capacitação Espermática , Motilidade Espermática , Mamíferos
18.
Brain Behav ; 13(1): e2836, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36563187

RESUMO

PURPOSE: To investigate the mechanism underlying the regulatory effect of melatonin on chronic sleep deprivation-related cognitive impairment. METHODS: Chronic sleep deprivation (CSD) model was established using the MMPM method. After the model was established, melatonin receptor agonist and inhibitor were given, respectively. Water maze was conducted to record the escape latency and the duration of crossing the platform of space exploration. The concentration of TNF-α, IL-6, MDA, and SOD was measured by ELISA. Immunofluorescence was used to determine the expression level of CD86 and CD206, while the mRNA expression of Bax, Bcl-2, P65, IκB, and BMAL1 was detected by qPCR. Western blotting assay was utilized to determine the protein expression of Bax, Bcl-2, P65, p-P65, IκB, p-I κB, and BMAL1. RESULTS: Compared with the control, the escape latency was greatly increased on the second and third day, accompanied by the increased expression of TNF-α, IL-6, MDA, and SOD in serum. Furthermore, dramatically upregulated Bax, Bcl-2, P65, IκB, and CD86 were observed in the model group, accompanied by the declined expression level of BMAL1 and CD206. Compared with the model group, the escape latency was declined, the concentration of TNF-α, IL-6, MDA, and SOD was decreased, the expression level of Bax, Bcl-2, P65, IκB, and CD86 was declined, and the level of BMAL1 and CD206 was promoted by the treatment of the melatonin agonist, while the opposite results were observed under the treatment of the melatonin inhibitor. CONCLUSION: Melatonin upregulates BMAL1 to attenuate chronic sleep deprivation-related cognitive impairment by alleviating oxidative stress.


Assuntos
Disfunção Cognitiva , Melatonina , Humanos , Melatonina/farmacologia , Melatonina/uso terapêutico , Privação do Sono/complicações , Privação do Sono/tratamento farmacológico , Fatores de Transcrição ARNTL/genética , Fatores de Transcrição ARNTL/metabolismo , Fatores de Transcrição ARNTL/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6 , Proteína X Associada a bcl-2/metabolismo , Estresse Oxidativo , Disfunção Cognitiva/complicações , Superóxido Dismutase/metabolismo
19.
Life Sci ; 312: 121253, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36481166

RESUMO

AIMS: To investigate, in the liver of adult offspring, the possible effects of melatonin supplementation in the obese mother during pregnancy and lactation. MAIN METHODS: C57BL/6 females were fed with a control (C) or a high-fat (HF) diet and supplemented with melatonin (Mel) during the pregnancy and lactation, forming the groups: C, CMel, HF, and HFMel. After weaning until three months old, the offspring only received the C diet. KEY FINDINGS: The HF mothers and their offspring showed higher body weight (BW) than the C mothers and offspring. However, at 3-mo-old, BW was reduced in HFMel vs. HF offspring. Also, plasmatic and liver lipid markers increased in HF vs. C offspring but were reduced in HFMel vs. HF offspring. Liver lipid content was lessened in HFMel vs. HF offspring by 50 %. Also, lipid metabolism, pro-inflammatory and endoplasmic reticulum (ER) stress genes were higher expressed in HF vs. C offspring but reduced in HFMel vs. HF offspring. Contrarily, beta-oxidation and antioxidant enzyme genes were less expressed in HF vs. C offspring but improved in HFMel vs. HF offspring. Finally, AMPK/mTOR pathway genes, initially dysregulated in the HF, were restored in the HFMel offspring. SIGNIFICANCE: The obese mother leads to liver alterations in the offspring. Current findings demonstrated the maternal melatonin supplementation during pregnancy and lactation in adult offspring's liver. Consequently, the effects were seen in mitigating the liver's AMPK/mTOR pathway genes, lipogenesis, beta-oxidation, inflammation, oxidative stress, and ER stress, preventing liver disease progression in the offspring.


Assuntos
Fígado Gorduroso , Melatonina , Obesidade , Efeitos Tardios da Exposição Pré-Natal , Animais , Feminino , Camundongos , Gravidez , Proteínas Quinases Ativadas por AMP , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Estresse do Retículo Endoplasmático , Inflamação , Lipídeos , Fenômenos Fisiológicos da Nutrição Materna , Melatonina/farmacologia , Camundongos Endogâmicos C57BL , Mães , Estresse Oxidativo , Serina-Treonina Quinases TOR
20.
Theriogenology ; 197: 94-100, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36476507

RESUMO

The aim of this study was to investigate the effects of melatonin (MLT), reduced glutathione (GSH) and vitamin E (Vit. E) or their combinations on semen cryopreservation of Mediterranean buffalo. The quality parameters such as viability, abnormality rate, motility, structural integrity and the antioxidant capacity of frozen-thawed sperm were evaluated. The efficiency of frozen-thawed sperms in performing their functions was further analyzed by in vitro fertilization (IVF). In those separately supplemented groups, 0.2 mg/mL MLT, 0.2 mM GSH and 0.4 mg/mL Vit. E had the best effect on antioxidant capacity, kinetics and morphology, respectively. In addition, the cleavage, blastocyst and hatching blastocyst rates of IVF embryos were higher in 0.2 mg/mL MLT, 0.2 mM GSH, 0.2 and 0.4 mg/mL Vit. E groups than the blank control. Among the three combination groups, the kinetics and structure integrity of frozen-thawed sperms, cleavage, blastocyst and hatching blastocyst rates of IVF embryos were higher in 0.4 mg/mL Vit. E plus 0.2 mg/mL MLT group than the blank control group, revealed that this combination had comprehensive protection on frozen-thawed sperm of Mediterranean buffalo. These results support to develop special semen freezing extender containing an optimal choice of MLT, GSH and Vit. E, and to enhance the efficiency of frozen-thawed sperm of Mediterranean buffalo for IVF.


Assuntos
Bison , Melatonina , Preservação do Sêmen , Masculino , Animais , Sêmen , Vitamina E/farmacologia , Antioxidantes/farmacologia , Búfalos , Melatonina/farmacologia , Preservação do Sêmen/veterinária , Preservação do Sêmen/métodos , Motilidade Espermática , Espermatozoides , Criopreservação/veterinária , Criopreservação/métodos , Glutationa/farmacologia
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