Abstract
The aim of this study was to investigate the role of selenoprotein M (SelM) in endoplasmic reticulum stress and apoptosis in nickel-exposed mouse hearts and to explore the detoxifying effects of melatonin. At 21 d after intraperitoneal injection of nickel chloride (NiCl2) and/or melatonin into male wild-type (WT) and SelM knockout (KO) C57BL/6J mice, NiCl2 was found to induce changes in the microstructure and ultrastructure of the hearts of both WT and SelM KO mice, which were caused by oxidative stress, endoplasmic reticulum stress, and apoptosis, as evidenced by decreases in malondialdehyde (MDA) content and total antioxidant capacity (T-AOC) activity. Changes in the messenger RNA (mRNA) and protein expression of genes related to endoplasmic reticulum stress (activating transcription factor 4 (ATF4), inositol-requiring protein 1 (IRE1), c-Jun N-terminal kinase (JNK), and C/EBP homologous protein (CHOP)) and apoptosis (B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), Caspase-3, Caspase-9, and Caspase-12) were also observed. Notably, the observed damage was worse in SelM KO mice. Furthermore, melatonin alleviated the heart injury caused by NiCl2 in WT mice but could not exert a good protective effect in the heart of SelM KO mice. Overall, the findings suggested that the antioxidant capacity of SelM, as well as its modulation of endoplasmic reticulum stress and apoptosis, plays important roles in nickel-induced heart injury.
摘要
本研究旨在研究硒蛋白 M (SelM) 在由镍诱导的小鼠心脏内质网应激和细胞凋亡中的作用, 并探索褪黑素的解毒作用. 在对雄性野生型 (WT) 和 SelM 敲除型 (KO) C57BL/6J 小鼠腹腔注射氯化镍 (NiCl2)和/或褪黑素 21 天后, 我们发现 NiCl2能诱发WT和 SelM KO 小鼠心脏的微观结构和超微结构的变化, 并通过丙二醛 (MDA) 含量和总抗氧化能力 (T-AOC) 下降证明这些变化是由氧化应激、 内质网应激和细胞凋亡引起的. 同时, 我们观察到与内质网应激(激活转录因子 4 (ATF4)、 肌醇需要酶 1 (IRE1)、 c-Jun N-端激酶 (JNK) 和 C/EBP 同源蛋白 (CHOP)) 和细胞凋亡( B 细胞淋巴瘤 2 型蛋白 (Bcl-2)、 Bcl-2 相关蛋白 X (Bax)、 半胱氨酸-天冬氨酸蛋白酶 3 (Caspase-3)、 Caspase-9 和 Caspase-12) 相关基因的信使 RNA (mRNA) 和蛋白表达的变化. 值得注意的是, 这种损伤在 SelM KO 小鼠中更严重. 此外, 褪黑素减轻了 WT 小鼠由 NiCl2 引起的心脏损伤, 但对 SelM KO 小鼠的心脏却不能产生良好的保护作用. 综上所述, 本研究结果表明 SelM 的抗氧化能力以及它对内质网应激和细胞凋亡的调节在镍引起的心脏损伤中起着重要作用.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Data availability
The data underlying this article will be shared on reasonable request to the corresponding author.
References
Cai JZ, Huang JQ, Yang J, et al., 2022. The protective effect of selenoprotein M on non-alcoholic fatty liver disease: the role of the AMPKα1-MFN2 pathway and Parkin mitophagy. Cell Mol Life Sci, 79(7):354. https://doi.org/10.1007/s00018-022-04385-0
Cameron KS, Buchner V, Tchounwou PB, 2011. Exploring the molecular mechanisms of nickel-induced genotoxicity and carcinogenicity: a literature review. Rev Environ Health, 26(2):81–92. https://doi.org/10.1515/reveh.2011.012
Cao JW, Xu R, Wang FH, et al., 2023. Polyethylene microplastics trigger cell apoptosis and inflammation via inducing oxidative stress and activation of the NLRP3 inflammasome in carp gills. Fish Shellfish Immunol, 132: 108470. https://doi.org/10.1016/j.fsi.2022.108470
Chakrabarti SK, Bai CJ, 1999. Role of oxidative stress in nickel chloride-induced cell injury in rat renal cortical slices. Biochem Pharmacol, 58(9): 1501–1510. https://doi.org/10.1016/s0006-2952(99)00232-4
Chen Y, Jing HY, Chen MY, et al., 2021. Transcriptional profiling of exosomes derived from Staphylococcus aureus-infected bovine mammary epithelial cell line MAC-T by RNA-seq analysis. Oxid Med Cell Longev, 2021:8460355. https://doi.org/10.1155/2021/8460355
Chi QR, Luan YL, Zhang YM, et al., 2019. The regulatory effects of miR-138-5p on selenium deficiency-induced chondrocyte apoptosis are mediated by targeting SelM. Metallomics, 11(4):845–857. https://doi.org/10.1039/c9mt00006b
Das KK, Reddy RC, Bagoji IB, et al., 2018. Primary concept of nickel toxicity—an overview. J Basic Clin Physiol Pharmacol, 30(2):141–152. https://doi.org/10.1515/jbcpp-2017-0171
Dong WX, Yan LQ, Tan Y, et al., 2022. Melatonin improves mitochondrial function by preventing mitochondrial fission in cadmium-induced rat proximal tubular cell injury via SIRT1-PGC-1α pathway activation. Ecotoxicol Environ Saf, 242:113879. https://doi.org/10.1016/j.ecoenv.2022.113879
Du XB, Li HP, Wang Z, et al., 2013. Selenoprotein P and selenoprotein M block Zn2+-mediated Aβ42 aggregation and toxicity. Metallomics, 5(7):861–870. https://doi.org/10.1039/c3mt20282h
Fan RF, Tang KK, Wang ZY, et al., 2021. Persistent activation of Nrf2 promotes a vicious cycle of oxidative stress and autophagy inhibition in cadmium-induced kidney injury. Toxicology, 464:152999. https://doi.org/10.1016/j.tox.2021.152999
Fernandez A, Ordóñez R, Reiter RJ, et al., 2015. Melatonin and endoplasmic reticulum stress: relation to autophagy and apoptosis. J Pineal Res, 59(3):292–307. https://doi.org/10.1111/jpi.12264
Genchi G, Carocci A, Lauria G, et al., 2020. Nickel: human health and environmental toxicology. Int J Environ Res Public Health, 17(3):679. https://doi.org/10.3390/ijerph17030679
Gong ZG, Zhao Y, Wang ZY, et al., 2022. Epigenetic regulator BRD4 is involved in cadmium-induced acute kidney injury via contributing to lysosomal dysfunction, autophagy blockade and oxidative stress. J Hazard Mater, 423:127110. https://doi.org/10.1016/j.jhazmat.2021.127110
Guo HR, Chen L, Cui HM, et al., 2016. Research advances on pathways of nickel-induced apoptosis. Int J Mol Sci, 17(1):10. https://doi.org/10.3390/ijms17010010
Kleszczyński K, Hardkop LH, Fischer TW, 2011. Differential effects of melatonin as a broad range UV-damage preventive dermato-endocrine regulator. Dermatoendocrinol, 3(1):27–31. https://doi.org/10.4161/derrrL3.1.14842
Kubrak OI, Poigner H, Husak VV, et al., 2014. Goldfish brain and heart are well protected from Ni2+-induced oxidative stress. Comp Biochem Physiol C Toxicol Pharmacol, 162: 43–50. https://doi.org/10.1016/j.cbpc.2014.03.011
Lee YK, Yim SY, Jung SE, et al., 2009. The costimulation of selenium treatment and selenoprotein M overexpression significantly induced the up- and down-regulation of ERK MAPK signaling pathway in various tissues. Lab Anim Res, 25(3):201–205.
Li JH, Zhang WY, Zhou P, et al., 2022. Selenium deficiency induced apoptosis via mitochondrial pathway caused by oxidative stress in porcine gastric tissues. Res Vet Sci, 144:142–148. https://doi.org/10.1016/j.rvsc.2021.10.017
Li XJ, Bai RC, Bai YC, et al., 2022. ROS-mediated PPAR/RXR inhibition contributes to acetochlor-induced apoptosis and autophagy in Ctenopharyngodon idella hepatic cells. Fish Shellfish Immunol, 128:684–694. https://doi.org/10.1016/jisi.2022.08.053
Li XY, Zhang HR, Qiao SQ, et al., 2022. Melatonin administration alleviates 2, 2,4,4-tetra-brominated diphenyl ether (PBDE-47)-induced necroptosis and secretion of inflammatory factors via miR-140-5p/TLR4/NF-κB axis in fish kidney cells. Fish Shellfish Immunol, 128:228–237. https://doi.org/10.1016/j.fsi.2022.08.004
Liu CM, Zheng GH, Ming QL, et al., 2013. Sesamin protects mouse liver against nickel-induced oxidative DNA damage and apoptosis by the PI3K-Akt pathway. J Agric Food Chem, 61(5):1146–1154. https://doi.org/10.1021/jf304562b
Liu JB, Li ZF, Lu L, et al., 2022. Glyphosate damages blood-testis barrier via NOX1-triggered oxidative stress in rats: long-term exposure as a potential risk for male reproductive health. Environ Int, 159:107038. https://doi.org/10.1016/j.envint.2021.107038
Liu Q, Sun Y, Zhu Y, et al., 2022a. Melatonin relieves liver fibrosis induced by Txnrd3 knockdown and nickel exposure via IRE1/NF-κB/NLRP3 and PERK/TGF-β1 axis activation. Life Sci, 301:120622. https://doi.org/10.1016/j.lfs.2022.120622
Liu Q, Du PY, Zhu Y, et al., 2022b. Thioredoxin reductase 3 suppression promotes colitis and carcinogenesis via activating pyroptosis and necrosis. Cell Mol Life Sci, 79(2): 106. https://doi.org/10.1007/s00018-022-04155-y
Liu XJ, Wang YQ, Shang SQ, et al., 2022. TMT induces apoptosis and necroptosis in mouse kidneys through oxidative stress-induced activation of the NLRP3 inflamma-some. Ecotoxicol Environ Saf, 230:113167. https://doi.org/10.1016/j.ecoenv.2022.113167
Lu JY, Zhang M, Jin HL, et al., 2014. Advances on molecular mechanism of chronic inflammation-driven lung cancer induced by environmental carcinogens. Prog Biochem Biophys, 41(1):41–51. https://doi.org/10.3724/spJ.1206.2013.00386
Lu W, Li WW, Jin XK, et al., 2012. Reproductive function of Selenoprotein M in Chinese mitten crabs (Eriocheir sinesis). Peptides, 34(1):168–176. https://doi.org/10.1016/j.peptides.2011.04.022
Miao ZR, Miao ZY, Shi X, et al., 2022a. The antagonistic effect of selenium on lead-induced apoptosis and necroptosis via P38/JNK/ERK pathway in chicken kidney. Ecotoxicol Environ Saf, 231:113176. https://doi.org/10.1016/j.ecoenv.2022.113176
Miao ZR, Miao ZY, Wang SC, et al., 2022b. Exposure to imidacloprid induce oxidative stress, mitochondrial dysfunction, inflammation, apoptosis and mitophagy via NF-kappaB/JNK pathway in grass carp hepatocytes. Fish Shellfish Immunol, 120:674–685. https://doi.org/10.1016/j.fsi.2021.12.017
Pitts MW, Hoffmann PR, 2018. Endoplasmic reticulum-resident selenoproteins as regulators of calcium signaling and homeostasis. Cell Calcium, 70:76–86. https://doi.org/10.1016/j.ceca.2017.05.001
Qiao SQ, Sun Y, Jiang YY, et al., 2022. Melatonin ameliorates nickel induced autophagy in mouse brain: diminution of oxidative stress. Toxicology, 473:153207. https://doi.org/10.1016/j.tox.2022.153207
Rehman K, Fatima F, Waheed I, et al., 2018. Prevalence of exposure of heavy metals and their impact on health consequences. J Cell Biochem, 119(1):157–184. https://doi.org/10.1002/jcb.26234
Roohbakhsh A, Shamsizadeh A, Hayes AW, et al., 2018. Melatonin as an endogenous regulator of diseases: the role of autophagy. Pharmacol Res, 133:265–276. https://doi.org/10.1016/j.phrs.2018.01.022
Selvik LKM, Fjeldbo CS, Flatberg A, et al., 2013. The duration of gastrin treatment affects global gene expression and molecular responses involved in ER stress and anti-apoptosis. BMC Genomics, 14:429. https://doi.org/10.1186/1471-2164-14-429
Song N, Wang W, Wang Y, et al., 2021. Hydrogen sulfide of air induces macrophage extracellular traps to aggravate inflammatory injury via the regulation of miR-15b-5p on MAPK and insulin signals in trachea of chickens. Sci Total Environ, 771:145407. https://doi.org/10.1016/j.scitotenv.2021.145407
Suresh C, Dennis AO, Heinz J, et al., 2006. Melatonin protection against lead-induced changes in human neuroblastoma cell cultures. Int J Toxicol, 25(6):459–464. https://doi.org/10.1080/10915810600959576
Wang CX, Zhang R, Wang S, et al., 2021. Protective effects of nano-selenium on nickel-induced renal cell apoptosis in rats. J Toxicol, 35(3): 193–197 (in Chinese). https://doi.org/10.16421/j.cnki.1002-3127.2021.03.004
Wang Y, Zhao HJ, Liu YC, et al., 2021. Environmentally relevant concentration of sulfamethoxazole-induced oxidative stress-cascaded damages in the intestine of grass carp and the therapeutic application of exogenous lycopene. Environ Pollut, 274:116597. https://doi.org/10.1016/j.envpol.2021.116597
Zhang HR, Zhao FQ, Gai XX, et al., 2022. Astilbin attenuates apoptosis induced by cadmium through oxidative stress in carp (Cyprinus carpio L.) head kidney lymphocyte. Fish Shellfish Immunol, 125:230–237. https://doi.org/10.1016/j.fsi.2022.05.021
Zhang WY, Sun XY, Shi X, et al., 2023. Subacute cadmium exposure induces necroptosis in swine lung via influencing Th1/Th2 balance. Biol Trace Elem Res, 201(1):220–228. https://doi.org/10.1007/s12011-022-03133-6
Zhang YH, Xu S, Li K, et al., 2023. TBBPA induced ROS overproduction promotes apoptosis and inflammation by inhibiting autophagy in mice lung. Ecotoxicol Environ Saf, 252:114607. https://doi.org/10.1016/j.ecoenv.2023.114607
Zhao HJ, Wang Y, Liu YC, et al., 2021. ROS-induced hepatotoxicity under cypermethrin: involvement of the crosstalk between Nrf2/Keap1 and NF-κB/iκB-α pathways regulated by proteasome. Environ Sci Technol, 55(9):6171–6183. https://doi.org/10.1021/acs.est.1c00515
Zheng YY, Guan HY, Yang J, et al., 2021. Calcium overload and reactive oxygen species accumulation induced by selenium deficiency promote autophagy in swine small intestine. Anim Nutr, 7(4):997–1008. https://doi.org/10.1016/j.aninu.2021.05.005
Acknowledgments
The work was supported by the Heilongjiang Provincial Natural Science Foundation for Outstanding Youth (No. YQ2021C021), China.
Author information
Authors and Affiliations
Contributions
Xintong ZHANG: writing - original draft; Xiaoxue GAI: data curation; Lihua XU: software; Wenxue MA: validation; Qiaohan LIU: visualization; Bendong SHI: methodology; Cheng FANG and Jingzeng CAI: writing - review & editing; Ziwei ZHANG: funding acquisition. All authors have read and approved the final manuscript, and therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.
Corresponding authors
Ethics declarations
Xintong ZHANG, Xiaoxue GAI, Lihua XU, Wenxue MA, Qiaohan LIU, Bendong SHI, Cheng FANG, Jingzeng CAI, and Ziwei ZHANG declare that they have no conflict of interests.
All procedures were carried out following the directive of the Council of the European Communities (No. 86/609/EEC) and approved by the Committee on Animal Management and Use of Northeast Agricultural University (No. SRM-11), China.
Rights and permissions
About this article
Cite this article
Zhang, X., Gai, X., Xu, L. et al. Role of selenoprotein M knockdown in the melatonin antagonism of nickel-induced apoptosis and endoplasmic reticulum stress in mouse heart. J. Zhejiang Univ. Sci. B 24, 406–417 (2023). https://doi.org/10.1631/jzus.B2200694
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1631/jzus.B2200694