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Cadmium exposure induces osteoporosis through cellular senescence, associated with activation of NF-κB pathway and mitochondrial dysfunction Full text
2021
Luo, Huigen | Gu, Renjie | Ouyang, Huiya | Wang, Lihong | Shi, Shanwei | Ji, Yuna | Bao, Baicheng | Liao, Guiqing | Xu, Baoshan
Cadmium (Cd) is a heavy metal toxicant as a common pollutant derived from many agricultural and industrial sources. The absorption of Cd takes place primarily through Cd-contaminated food and water and, to a significant extent, via inhalation of Cd-contaminated air and cigarette smoking. Epidemiological data suggest that occupational or environmental exposure to Cd increases the health risk for osteoporosis and spontaneous fracture such as itai-itai disease. However, the direct effects and underlying mechanism(s) of Cd exposure on bone damage are largely unknown. We used primary bone marrow-derived mesenchymal stromal cells (BMMSCs) and found that Cd significantly induced BMMSC cellular senescence through over-activation of NF-κB signaling pathway. Increased cell senescence was determined by production of senescence-associated secretory phenotype (SASP), cell cycle arrest and upregulation of p21/p53/p16ᴵᴺᴷ⁴ᵃ protein expression. Additionally, Cd impaired osteogenic differentiation and increased adipogenesis of BMMSCs, and significantly induced cellular senescence-associated defects such as mitochondrial dysfunction and DNA damage. Sprague-Dawley (SD) rats were chronically exposed to Cd to verify that Cd significantly increased adipocyte number, and decreased mineralization tissues of bone marrow in vivo. Interestingly, we observed that Cd exposure remarkably retarded bone repair and regeneration after operation of skull defect. Notably, pretreatment of melatonin is able to partially prevent Cd-induced some senescence-associated defects of BMMSCs including mitochondrial dysfunction and DNA damage. Although Cd activated mammalian target of rapamycin (mTOR) pathway, rapamycin only partially ameliorated Cd-induced cell apoptosis rather than cellular senescence phenotypes of BMMSCs. In addition, a selective NF-κB inhibitor moderately alleviated Cd-caused the senescence-related defects of the BMMSCs. The study shed light on the action and mechanism of Cd on osteoporosis and bone ageing, and may provide a novel option to ameliorate the harmful effects of Cd exposure.
Show more [+] Less [-]COMT1 overexpression resulting in increased melatonin biosynthesis contributes to the alleviation of carbendazim phytotoxicity and residues in tomato plants Full text
2019
Yan, Yanyan | Sun, Shasha | Zhao, Ning | Yang, Wanying | Shi, Qinghua | Gong, Biao
Melatonin (Mel) serves as an important signalling molecule in various aspects of stress tolerance in plants. However, the function of Mel in pesticide metabolism remains unknown. Here, selecting the widely used fungicide carbendazim (MBC) as the model, we found that exogenous Mel had the ability to alleviate pesticide phytotoxicity and residues in tomato as well as in some other vegetables. Additionally, overexpression of the Mel biosynthetic gene caffeic acid O-methyltransferase 1 (COMT1) significantly enhanced the capacity of the tomato to reduce MBC phytotoxicity and residue. This outcome was mainly because of the Mel-induced antioxidant capability, as well as the key detoxification process. Indeed, levels of reactive oxygen species (ROS) and lipid peroxides significantly decreased after applying exogenous Mel or overexpressing COMT1, which resulted from direct ROS scavenging, and increased Mel levels significantly enhanced antioxidant enzymatic activity. More importantly, Mel activated the ascorbate-glutathione cycle to participate in glutathione S-transferase-mediated pesticide detoxification. A grafting experiment showed that rootstocks from COMT1 transgenic plants increased the Mel accumulation of wild-type scions, resulting in MBC metabolism in the scions. To our knowledge, this is the first report providing evidence of Mel-induced pesticide metabolism, which provides a novel approach for minimizing pesticide residues in crops by exploiting plant self-detoxification mechanisms.
Show more [+] Less [-]Metabolomics analysis of a mouse model for chronic exposure to ambient PM2.5 Full text
2019
Xu, Yanyi | Wang, Wanjun | Zhou, Ji | Chen, Minjie | Huang, Xingke | Zhu, Yaning | Xie, Xiaoyun | Li, Weihua | Zhang, Yuhao | Kan, Haidong | Ying, Zhekang
Chronic ambient fine particulate matter (PM₂.₅) exposure correlates with various adverse health outcomes. Its impact on the circulating metabolome−a comprehensive functional readout of the interaction between an organism's genome and environment−has not however been fully understood. This study thus performed metabolomics analyses using a chronic PM₂.₅ exposure mouse model. C57Bl/6J mice (female) were subjected to inhalational concentrated ambient PM₂.₅ (CAP) or filtered air (FA) exposure for 10 months. Their sera were then analyzed by liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). These analyses identified 2570 metabolites in total, and 148 of them were significantly different between FA- and CAP-exposed mice. The orthogonal partial least-squares discriminant analysis (OPLS-DA) and heatmap analyses displayed evident clustering of FA- and CAP-exposed samples. Pathway analyses identified 6 perturbed metabolic pathways related to amino acid metabolism. In contrast, biological characterization revealed that 71 differential metabolites were related to lipid metabolism. Furthermore, our results showed that CAP exposure increased stress hormone metabolites, 18-oxocortisol and 5a-tetrahydrocortisol, and altered the levels of circadian rhythm biomarkers including melatonin, retinal and 5-methoxytryptophol.
Show more [+] Less [-]Illuminated night alters behaviour and negatively affects physiology and metabolism in diurnal zebra finches Full text
2019
Batra, Twinkle | Malik, Indu | Kumar, Vinod
Light at night (LAN) negatively impacts the behaviour and physiology; however, very little is known about molecular correlates of LAN-induced effects in diurnal animals. Here, we assessed LAN-induced effects on behaviour and physiology, and examined molecular changes in the liver of diurnal zebra finches (Taeniopygia guttata). Birds were exposed to dim LAN (dLAN: 12L = 150 lux: 12D = 5 lux), with controls on 12L (150 lux): 12D (0 lux). dLAN altered daily activity-rest and eating patterns, induced nocturnal eating and caused body fattening and weight gain, and reduced nocturnal melatonin levels. Concomitant increased nighttime glucose levels, decreased daytime thyroxine and triglycerides levels, and hepatic lipid accumulation suggested the impairment of metabolism under dLAN. Transcriptional assays evidenced dLAN-induced negative effects on metabolism in the liver, the site of metabolic homeostasis. Particularly, increased g6pc and foxo1 mRNA expressions suggested an enhanced gluconeogenesis, while increased egr1 and star expressions suggested enhanced cholesterol biosynthesis and lipid metabolism, respectively. Similarly, overexpressed sirt1 indicated protection from the metabolic damage due to elevated gluconeogenesis and cholesterol biosynthesis under dLAN. However, no effect on genes involved in lipogenesis (fasn) and insulin signalling pathway (socs3 and insig1) might indicate for the post transcriptional/post translational modification effects or the involvement of other genetic pathways in LAN-induced effects. We also found daily rhythm in the hepatic expression of selected clock and clock-controlled genes (per2, bmal1 and reverb-beta), with an elevated mesor and amplitude of per2 oscillation, suggesting a role of per2 in the liver metabolism. These results demonstrate dLAN-induced negative effects on the behaviour and physiology, and provide molecular insights into metabolic risks of the exposure to illuminated nights to diurnal animals including humans in an urban setting.
Show more [+] Less [-]ATM signals to AMPK to promote autophagy and positively regulate DNA damage in response to cadmium-induced ROS in mouse spermatocytes Full text
2017
Li, Renyan | Luo, Xue | Zhu, Yijian | Zhao, Letian | Li, Lianbing | Peng, Qiang | Ma, Mingfu | Gao, Yanfei
Cadmium (Cd) is a toxic heavy metal and harmful to human health due to its ability to accumulate in organs. Previous studies have shown that Cd can induce DNA damage and autophagy. Autophagy can stabilize genetic material and DNA integrity. The aim of the present study was to determine the exact mechanism and role of autophagy induced by Cd in spermatozoa cells. Mouse spermatocyte-derived cells (GC-2) were treated with 20 μM Cd chloride for 24 h. The level of reactive oxygen species (ROS), DNA damage, autophagy and the expression of the molecular signaling pathway ATM/AMP-activated protein kinase (AMPK)/mTOR were determined. The results showed that Cd induced autophagy and DNA damage in GC-2 cells via ROS generation, and the autophagy signal pathway AMPK/mTOR was activated by ATM which is a DNA damage sensor. Melatonin, a well-known antioxidant, ameliorated DNA damage, and inhibited autophagy via the AMPK/mTOR signal pathway. Furthermore, after inhibition of autophagy by knockdown of AMPKα, increased DNA damage by Cd treatment was observed in GC-2 cells. These findings demonstrated the protective role of autophagy in DNA damage and suggested that the mechanism of autophagy induced by Cd was through the ATM/AMPK/mTOR signal pathway in spermatozoa cells.
Show more [+] Less [-]The combined supplementation of melatonin and salicylic acid effectively detoxifies arsenic toxicity by modulating phytochelatins and nitrogen metabolism in pepper plants Full text
2022
Kaya, Cengiz | Sarıoglu, Ali | Ashraf, Muhammad | Alyemeni, Mohammed Nasser | Ahmad, Parvaiz
The main objective of the study was to assess if joint application of melatonin (MT, 0.1 mM) and salicylic acid (SA 0.5 mM) could improve tolerance of pepper plants to arsenic (As) as sodium hydrogen arsenate heptahydrate (0.05 mM). The imposition of arsenic stress led to accumulation of As in roots and leaves, and increased contents of leaf proline, phytochelatins, malondialdehyde (MDA) and H₂O₂, but it reduced plant biomass, chlorophylls (Chl), PSII maximum efficiency (Fv/Fm) and leaf water potential. Melatonin and SA applied jointly or alone enhanced nitrogen metabolism by triggering the activities of glutamate synthase, glutamine synthetase, and nitrite reductases and nitrate. In comparison with a single treatment of MT or SA, the joint treatment of MT and SA had better impact on enhancing growth and key biological events and decreasing tissue As content. This clearly shows a cooperative function of both agents in enhancing tolerance to As-toxicity in pepper plants.
Show more [+] Less [-]Exogenous melatonin protects preimplantation embryo development from decabromodiphenyl ethane-induced circadian rhythm disorder and endogenous melatonin reduction Full text
2022
Shi, Feifei | Qiu, Jinyu | Zhang, Shaozhi | Zhao, Xin | Feng, Daofu | Feng, Xizeng
Decabromodiphenyl ethane (DBDPE) is a novel flame retardant that is widely used in plastics, electronic products, building materials and textiles. Our previous studies have revealed the oocyte toxicity of DBDPE, but the effect of DBDPE on preimplantation embryo development has not been reported. Here, we investigated whether and how DBDPE exposure affects preimplantation embryo development. Adult female mice were orally exposed to DBDPE (0, 5, 50, 500 μg/kg bw/day) for 14 days. First, we found that after DBDPE exposure, mice showed obvious circadian rhythm disorder. Moreover, the development of preimplantation embryos was inhibited in DBDPE-exposed mice after pregnancy. Then, we further explored and revealed that DBDPE exposure reduced the endogenous melatonin (MLT) level during pregnancy, thereby inhibiting the development of preimplantation embryos. Furthermore, we discovered that exogenous MLT supplementation (15 mg/kg bw/day) rescued the inhibition of preimplantation embryo development induced by DBDPE, and a mechanistic study demonstrated that exogenous MLT inhibited the overexpression of ROS and DNA methylation at the 5-position of cytosine (5-mC) in DBDPE-exposed preimplantation embryos. Simultaneously, MLT ameliorated the DBDPE-induced mitochondrial dysfunction by increasing the mitochondrial membrane potential (MMP), ATP, and Trp1 expression. Additionally, MLT restored DBDPE-induced changes in zona pellucida (ZP) hardness and trophectoderm (TE) cortical tension. Finally, the protective effect of MLT on embryos ameliorated the adverse reproductive outcomes (dead fetus, fetus with abnormal liver, fetal weight loss) induced by DBDPE. Collectively, DBDPE induced preimplantation embryo damage leading to adverse reproductive outcomes, and MLT has emerged as a potential tool to rescue adverse reproductive outcomes induced by DBDPE.
Show more [+] Less [-]Mitigation effects of exogenous melatonin-selenium nanoparticles on arsenic-induced stress in Brassica napus Full text
2022
Farooq, Muhammad Ahsan | Islam, Faisal | Ayyaz, Ahsan | Chen, Weiqi | Noor, Yamna | Hu, Weizhen | Hannan, Fakhir | Zhou, Weijun
Melatonin (MT) and selenium (Se) application known to decrease heavy metal uptake and toxicity in plants. By mixing the Se in MT medium a new complex MT-Se nanoparticles (MT-Se NPs) was synthesized and we investigated the role of MT-Se NPs on B. napus growth and tolerance against As stress. The MT-Se particles significantly enhanced the plant growth and other associated physiological attributes under As stress. The As treatment at 80 μM was more phytotoxic, however MT-Se NPs application resulted in a substantial increase in leaf chlorophyll fluorescence, biomass accumulation, and decreased ROS relative to As stressed plants. The use of MT-Se NPs to As stressed plants reduced photosynthetic inhibition and oxidative stress and attenuated the increase in MDA and H₂O₂ contents. The application of MT-Se NPs also boosted the antioxidant enzymes activities such as SOD, POD and CAT as well as the APX, GR and GSH activates under As stress. The results also showed MT-Se NPs treatments alleviated the growth inhibition induced by As and reduced the accumulation of As in leaves and roots of B. napus seedlings. Moreover, treatment with MT-Se NPs improved the plant growth more successfully than treatment of MT and Se alone. This study explored the mechanism of melatonin and selenium efficiency in the composition can be jointly encouraged to exert synergistic effects and boost plant enzymatic activities.
Show more [+] Less [-]Melatonin enhanced oilseed rape growth and mitigated Cd stress risk: A novel trial for reducing Cd accumulation by bioenergy crops Full text
2022
Menhas, Saiqa | Yang, Xijia | Hayat, Kashif | Ali, Amjad | Ali, Esmat F. | Shāhid, Muḥammad | Shaheen, Sabry M. | Rinklebe, Jörg | Hayat, Sikandar | Zhou, Pei
Melatonin (M) is a pleiotropic molecule that improves plant growth and increases heavy metal tolerance. The role of M for improving plant growth and tolerance under cadmium (Cd) stress, and mitigation of Cd-induced toxicity has not yet been sufficiently examined. Therefore, here we conducted a glasshouse experiment to explore the influence of various M dosages on Cd detoxification and stress-tolerance responses of Brassica napus under high Cd content (30 mg kg⁻¹). The effects of M on the modulation of Cd tolerance in B. napus plants have been investigated using various growth attributes, Cd accumulation and tolerance indices, and secondary metabolic parameters. We found that Cd stress inhibited root growth (by 11.9%) as well as triggered reactive oxygen species accumulation (by 31.2%) and MDA levels (by 18.7%); however, exogenous M substantially alleviated the adverse effect of oxidative stress by decreasing levels of H₂O₂ (by 38.7%), MDA (by 13.8%) and EL (by 1.8%) in the Cd-stressed plants, as compared to the M-untreated plants (control). Interestingly, exogenous M reduced Cd accumulation in roots (∼48.2–58.3-fold), stem (∼2.9–5.0-fold) and leaves (∼4.7–6.6-fold) compared to control plants, which might be due to an M-induced defense and/or detoxification response involving a battery of antioxidants. Overall, addition of the exogenous M to the Cd-stressed plants profoundly enhanced Cd tolerance in B. napus relative to control plants. These results suggested the biostimulatory role (at the physiological and molecular level) of M in improving growth, Cd tolerance, and Cd detoxification in B. napus, which indicate the potentiality of M for green remediation of Cd contaminated soils. This green trial would provide a reference for producing renewable bioenergy crops under Cd stress in contaminated soils. However, these recommendations should be verified under field conditions and the potential mechanisms for the interaction between Cd and M should be explicitly explored.
Show more [+] Less [-]Effects of dim artificial light at night on locomotor activity, cardiovascular physiology, and circadian clock genes in a diurnal songbird Full text
2021
Alaasam, Valentina J. | Liu, Xu | Niu, Ye | Habibian, Justine S. | Pieraut, Simon | Ferguson, Brad S. | Zhang, Yong | Ouyang, Jenny Q.
Artificial light is transforming the nighttime environment and quickly becoming one of the most pervasive pollutants on earth. Across taxa, light entrains endogenous circadian clocks that function to synchronize behavioral and physiological rhythms with natural photoperiod. Artificial light at night (ALAN) disrupts these photoperiodic cues and has consequences for humans and wildlife including sleep disruption, physiological stress and increased risk of cardiovascular disease. However, the mechanisms underlying organismal responses to dim ALAN, resembling light pollution, remain elusive. Light pollution exists in the environment at lower levels (<5 lux) than tested in many laboratory studies that link ALAN to circadian rhythm disruption. Few studies have linked dim ALAN to both the upstream regulators of circadian rhythms and downstream behavioral and physiological consequences. We exposed zebra finches (Taeniopygia gutatta) to dim ALAN (1.5 lux) and measured circadian expression of five pacemaker genes in central and peripheral tissues, plasma melatonin, locomotor activity, and biomarkers of cardiovascular health. ALAN caused an increase in nighttime activity and, for males, cardiac hypertrophy. Moreover, downstream effects were detectable after just short duration exposure (10 days) and at dim levels that mimic the intensity of environmental light pollution. However, ALAN did not affect circulating melatonin nor oscillations of circadian gene expression in the central clock (brain) or liver. These findings suggest that dim ALAN can alter behavior and physiology without strong shifts in the rhythmic expression of molecular circadian pacemakers. Approaches that focus on ecologically-relevant ALAN and link complex biological pathways are necessary to understand the mechanisms underlying vertebrate responses to light pollution.
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