Selenium Reduces Lipopolysaccharide-Induced Apoptosis and Oxidative Stress Through the Inhibition of TRPM7 Channel in Neuronal Cells

Müge Mavioğlu Kaya

doi:10.37212/jcnos.1846970

Selenium Reduces Lipopolysaccharide-Induced Apoptosis and Oxidative Stress Through the Inhibition of TRPM7 Channel in Neuronal Cells

Abstract

The trace element selenium (Se) has anti-apoptotic and antioxidant properties. When stimulated by lipopolysaccharide (LPS), brain and neural cells undergo apoptosis and produce reactive oxygen species (ROS). LPS-induced ROS stimulates transient receptor potential melastatin 7 (TRPM7) activation, whereas carvacrol (CRV) and Se inhibit it. The mechanisms by which Se inhibits LPS-induced oxidative stress and apoptosis in neuronal (SH-SY5Y) cells remain unknown. To protect SH-SY5Y cells from ROS-induced apoptosis and death, I investigated how Se alters the TRPM7-mediated molecular pathways. Five main groups were generated in the SH-SY5Y:Control, Se (1 μM for 2 hours), LPS (1 μg/ml for 24 hours), LPS + Se, and LPS + TRPM7 blocker (CRV). Apoptosis, ROS, mitochondrial dysfunction, apoptotic markers (caspase-3, -8, and -9), and cytosolic free Ca2+ were increased by the LPS incubation, whereas Se and CRV treatments reduced these parameters. The LPS decreased cell viability; however, the viability in the LPS + Se and LPS + CRV groups increased with the incubations of Se and CRV. In conclusion, Se decreased LPS-induced oxidative stress and apoptosis by inhibiting TRPM7 in the neuronal cells. One possible treatment agent for oxidative neuronal injury and neurodegenerative disorders induced by LPS could be the Se treatment.

Keywords

Supporting Institution

This study was funded by BSN Health, Analyses, Innov., Consult., Org., Agricul., Trade Ltd., Isparta, Türkiye (Project No: 2024-04).

Project Number

2024-04

Ethical Statement

There are no samples of humans, living animals, or higher invertebrates

References

Aydın B, Nazıroğlu M. (2023). Involvement of TRPM7 Channel on the Induction of Diabetic Neuropathic Pain in Mice: Protective Role of Selenium and Curcumin. Biol Trace Elem Res. 201(5):2377- 2395. https://doi.org/10.1007/s12011-022-03518-7.
Busey GW, Manjegowda MC, Huang T, et al. (2024). Analogs of FTY720 inhibit TRPM7 but not S1PRs and exert multimodal antiinflammatory effects. J Gen Physiol. 156(1):e202313419. https://doi.org/10.1085/jgp.202313419.
Chen D, Liu H, Sun W, Xu S. (2025). Selenomethionine alleviates LPS-induced PANoptosis in chicken cecum through the ROS/MAPK pathway, thereby mitigating inflammation and microbial dysbiosis. Poult Sci. 104(9):105392. https://doi.org/10.1016/j.psj.2025.105392.
Chen D, Sun W, Liu H, et al. (2024). SeMet alleviates LPS-induced eggshell gland necroptosis mediated inflammation by regulating the Keap1/Nrf2/HO-1 pathway. Arch Biochem Biophys. 751:109847. https://doi.org/10.1016/j.abb.2023.109847.
Çiğ B. (2025). Selenium reduces oxaliplatin induced neuropathic pain:focus on TRPV1. Front Pharmacol. 16:1549190. https://doi.org/10.3389/fphar.2025.1549190.
Çınar R, Yıldızhan K. (2025). Curcumin protects against MPP+-induced neurotoxicity in SH-SY5Y cells by modulating the TRPV4 channel. Mol Biol Rep. 52(1):255. https://doi.org/10.1007/s11033-025-10345-1.
Çınar R. (2022). Depletion of glutathione induced apoptosis and oxidative stress via the activation of TRPM2 channels in the microglia cells with Alzheimer’ disease model. J Cell Neurosci Oxid Stress. 14(1): 1063-1073. https://doi.org/10.37212/jcnos.1147935.
de Araújo Boleti AP, de Oliveira Flores TM, Moreno SE, Anjos LD, Mortari MR, Migliolo L. (2020). Neuroinflammation: An overview of neurodegenerative and metabolic diseases and of biotechnological studies. Neurochem Int. 136:104714. https://doi.org/10.1016/j.neuint.2020.104714.

Deng W, Ren G, Luo J, Gao S, Huang W, Liu W, Ye S. (2023). TRPM7 mediates endoplasmic reticulum stress and ferroptosis in sepsisinduced myocardial injury. J Bioenerg Biomembr. 55(3):207-217. https://doi.org/10.1007/s10863-023-09968-5.
Ertilav K, Nazıroğlu M. (2025). Inhibition of TRPM7 by glutathione decreases oxidant and apoptotic action of cisplatin through the downregulation of Ca2+ and Zn2+ in glioblastoma cells. Adv Med Sci. 70(1):124-135. https://doi.org/10.1016/j.advms.2025.01.008.
Ghosh M, Pearse DD. (2024). The Yin and Yang of Microglia-Derived Extracellular Vesicles in CNS Injury and Diseases. Cells. 13(22):1834. https://doi.org/10.3390/cells13221834.
Hegazy AA, Domouky AM, Akmal F, El-Wafaey DI. (2023). Possible role of selenium in ameliorating lead-induced neurotoxicity in the cerebrum of adult male rats: an experimental study. Sci Rep. 13(1):15715. https://doi.org/10.1038/s41598-023-42319-3.
Hofmann T, Schäfer S, Linseisen M, Sytik L, Gudermann T, Chubanov V. (2014). Activation of TRPM7 channels by small molecules under physiological conditions. Pflugers Arch. 466(12):2177-2189. https://doi.org/10.1007/s00424-014-1488-0.
Hu Y, Yan Z, He Y, et al. (2023). Ameliorative effects of different doses of selenium against fluoride-triggered apoptosis and oxidative stress-mediated renal injury in rats through the activation of Nrf2/HO-1/NQO1 signaling pathway. Food Chem Toxicol. 174:113647. https://doi.org/10.1016/j.fct.2023.113647.
Huang Y, Jia Z, Xu Y, Qin M, Feng S. (2020). Selenium protects against LPS-induced MC3T3-E1 cells apoptosis through modulation of microRNA-155 and PI3K/Akt signaling pathways. Genet Mol Biol. 43(3):e20190153. https://doi.org/10.1590/1678-4685-GMB-2019-0153.
Joshi DC, Bakowska JC. (2011). Determination of mitochondrial membrane potential and reactive oxygen species in live rat cortical neurons. J Vis Exp. 51: 2704. https://doi.org/10.3791/2704.
Kaya MM. (2024). Silver nanoparticles stimulate 5-Fluorouracil-induced colorectal cancer cells to kill through the upregulation TRPV1-mediated calcium signaling pathways. Cell Biol Int. 48(5):712- 725. https://doi.org/10.1002/cbin.12141.
Leong HS, Philp M, Simone M, Witting PK, Fu S. (2020). Synthetic Cathinones Induce Cell Death in Dopaminergic SH-SY5Y Cells via Stimulating Mitochondrial Dysfunction. Int J Mol Sci. 21(4):1370. https://doi.org/10.3390/ijms21041370.
Macianskiene R, Martisiene I, Zablockaite D, Gendviliene V. (2012). Characterization of Mg²⁺-regulated TRPM7-like current in human atrial myocytes. J Biomed Sci. 19(1):75. doi: 10.1186/1423-0127-19-75.
Mandlem VKK, Rivera A, Khan Z, Quazi SH, Deba F. (2024). TLR4 induced TRPM2 mediated neuropathic pain. Front Pharmacol. 15:1472771. https://doi.org/10.3389/fphar.2024.1472771.
Nazıroğlu M, Öz A, Yıldızhan K. (2020). Selenium and Neurological Diseases: Focus on Peripheral Pain and TRP Channels. Curr Neuropharmacol. 18(6):501-517. https://doi.org/10.2174/1570159X18666200106152631. Oh HG, Chun YS, Park CS, Kim TW, Park MK, Chung S. (2015).
Regulation of basal autophagy by transient receptor potential melastatin 7 (TRPM7) channel. Biochem Biophys Res Commun. 463(1-2):7-12. https://doi.org/10.1016/j.bbrc.2015.05.007.
Oh HG, Chung S. (2017). Activation of transient receptor potential melastatin 7 (TRPM7) channel increases basal autophagy and reduces amyloid β-peptide. Biochem Biophys Res Commun. 493(1):494-499. https://doi.org/10.1016/j.bbrc.2017.08.163.
Osmanlıoğlu HÖ, Nazıroğlu M. (2025). Morphine inhibits the TRPM2 signaling pathways in microglia cells, reducing the increases in oxidative stress, cytokines, and cell death caused by lipopolysaccharide. Immunopharmacol Immunotoxicol. 47(5):687-701. https://doi.org/10.1080/08923973.2025.2555475
Öz A, Çelik Ö. (2022). The effects of neuronal cell differentiation on TRPM7, TRPM8 and TRPV1 channels in the model of Parkinson's disease. Neurol Res. 44(1):24-37. https://doi.org/10.1080/01616412.2021.1952512.
Öz A, Çelik Ö. (2023). Downregulation of TRPM7, TRPM8, and TRPV1 channels modulate apoptotic parameters and neurodegenerative markers: Focus on neuronal differentiation and Parkinson's disease model. Cell Biol Int. 47(9):1502-1518. https://doi.org/10.1002/cbin.12048.
Perlikowska R, Długosz-Pokorska A, Domowicz M, Grabowicz S, Stasiołek M, Zakłos-Szyda M. (2025). Reduction in SH-SY5Y Cell Stress Induced by Corticosterone and Attenuation of the Inflammatory Response in RAW 264.7 Cells Using Endomorphin Analogs. Biomedicines. 13(7):1774. https://doi.org/10.3390/biomedicines13071774.
Qu L, Ji L, Wang C, et al. (2021). Synthesis and evaluation of multitarget-directed ligands with BACE-1 inhibitory and Nrf2 agonist activities as potential agents against Alzheimer's disease. Eur J Med Chem. 219:113441. https://doi.org/10.1016/j.ejmech.2021.113441.
Shademan B, Yousefi H, Sharafkhani R, Nourazarian A. (2025). LPSInduced Neuroinflammation Disrupts Brain-Derived Neurotrophic Factor and Kinase Pathways in Alzheimer's Disease Cell Models. Cell Mol Neurobiol. 45(1):102. https://doi.org/10.1007/s10571-025-01600-x.
Ullah S, Park TJ, Park JS, et al. (2025). Ambroxol attenuates detrimental effect of LPS-induced glia-mediated neuroinflammation, oxidative stress, and cognitive dysfunction in mice brain. Front Immunol. 16:1494114. https://doi.org/10.3389/fimmu.2025.1494114.
Wang H, Sun S, Ren Y, et al. (2023). Selenite Ameliorates Cadmiuminduced Cytotoxicity Through Downregulation of ROS Levels and Upregulation of Selenoprotein Thioredoxin Reductase 1 in SHSY5Y Cells. Biol Trace Elem Res. 201(1):139-148. https://doi.org/10.1007/s12011-022-03117-6.
Wu X, Huang P, Xiao Y, Zha L, Ma J, Xiao H. (2024). METTL14 Promotes Lipopolysaccharide-Induced Myocardial Damage via m6A-Dependent Stabilization of TRPM7 mRNA. Int Heart J. 65(6):1118-1127. https://doi.org/10.1536/ihj.24-162.
Yıldızhan K, Nazıroğlu M. (2022). Protective role of selenium on MPP+ and homocysteine-induced TRPM2 channel activation in SHSY5Y cells. J Recept Signal Transduct Res. 42(4):399-408. https://doi.org/10.1080/10799893.2021.1981381.

Details

Primary Language

English

Subjects

Biochemistry and Cell Biology (Other)

Journal Section

Research Article

Authors

Müge Mavioğlu Kaya ^*
0000-0003-1276-3745
Türkiye

Publication Date

February 11, 2026

Submission Date

December 22, 2025

Acceptance Date

February 8, 2026

Published in Issue

Year 2025 Volume: 17 Number: 3

DOI

https://doi.org/10.37212/jcnos.1846970

IZ

https://izlik.org/JA48GJ54YP

Cite

RIS / Bibtex

APA

Mavioğlu Kaya, M. (2026). Selenium Reduces Lipopolysaccharide-Induced Apoptosis and Oxidative Stress Through the Inhibition of TRPM7 Channel in Neuronal Cells. Journal of Cellular Neuroscience and Oxidative Stress, 17(3), 1283-1291. https://doi.org/10.37212/jcnos.1846970

AMA

1.Mavioğlu Kaya M. Selenium Reduces Lipopolysaccharide-Induced Apoptosis and Oxidative Stress Through the Inhibition of TRPM7 Channel in Neuronal Cells. J Cell Neurosci Oxid Stress. 2026;17(3):1283-1291. doi:10.37212/jcnos.1846970

Chicago

Mavioğlu Kaya, Müge. 2026. “Selenium Reduces Lipopolysaccharide-Induced Apoptosis and Oxidative Stress Through the Inhibition of TRPM7 Channel in Neuronal Cells”. Journal of Cellular Neuroscience and Oxidative Stress 17 (3): 1283-91. https://doi.org/10.37212/jcnos.1846970.

EndNote

Mavioğlu Kaya M (February 1, 2026) Selenium Reduces Lipopolysaccharide-Induced Apoptosis and Oxidative Stress Through the Inhibition of TRPM7 Channel in Neuronal Cells. Journal of Cellular Neuroscience and Oxidative Stress 17 3 1283–1291.

IEEE

[1]M. Mavioğlu Kaya, “Selenium Reduces Lipopolysaccharide-Induced Apoptosis and Oxidative Stress Through the Inhibition of TRPM7 Channel in Neuronal Cells”, J Cell Neurosci Oxid Stress, vol. 17, no. 3, pp. 1283–1291, Feb. 2026, doi: 10.37212/jcnos.1846970.

ISNAD

Mavioğlu Kaya, Müge. “Selenium Reduces Lipopolysaccharide-Induced Apoptosis and Oxidative Stress Through the Inhibition of TRPM7 Channel in Neuronal Cells”. Journal of Cellular Neuroscience and Oxidative Stress 17/3 (February 1, 2026): 1283-1291. https://doi.org/10.37212/jcnos.1846970.

JAMA

1.Mavioğlu Kaya M. Selenium Reduces Lipopolysaccharide-Induced Apoptosis and Oxidative Stress Through the Inhibition of TRPM7 Channel in Neuronal Cells. J Cell Neurosci Oxid Stress. 2026;17:1283–1291.

MLA

Mavioğlu Kaya, Müge. “Selenium Reduces Lipopolysaccharide-Induced Apoptosis and Oxidative Stress Through the Inhibition of TRPM7 Channel in Neuronal Cells”. Journal of Cellular Neuroscience and Oxidative Stress, vol. 17, no. 3, Feb. 2026, pp. 1283-91, doi:10.37212/jcnos.1846970.

Vancouver

1.Müge Mavioğlu Kaya. Selenium Reduces Lipopolysaccharide-Induced Apoptosis and Oxidative Stress Through the Inhibition of TRPM7 Channel in Neuronal Cells. J Cell Neurosci Oxid Stress. 2026 Feb. 1;17(3):1283-91. doi:10.37212/jcnos.1846970