Lipopolysaccharide induces apoptosis and oxidative cytotoxicity through stimulation of the TRPV1 channel in retinal pigment epithelium cell line
Year 2024,
Volume: 16 Issue: 3, 1229 - 1236, 13.01.2025
Ertuğrul Alper
Abstract
Common and vision-threatening inflammatory ocular disorders are major issues on a global scale. The etiology and whole treatment for inflammatory disorders are yet unknown. With the exception of human retinal pigment epithelial-19 (ARPE-19), numerous cells have been shown to be involved in lipopolysaccharide (LPS)-induced free reactive oxygen species (ROS) and apoptosis through TRPV1 cation channel stimulation. I wanted to determine how TRPV1 affected the oxidative cytotoxicity and apoptosis caused by LPS in ARPE-19.
Two main groups in the ARPE-19 cells were induced as control and LPS (1 g/ml for twenty-four hours). TRPV1 antagonist (100 M capsazepine (CAPZ) for 1 hour) blocked TRPV1 in the channel, whereas TRPV1 agonist (10 M capsaicin (CAPS) for 1 hour) stimulated cells of the main groups.
The incubation of CAPS increased the amounts of apoptosis, caspases (caspase -3, -8, and -9), mitochondrial dysfunction, and ROS in the control and LPS groups, while CAPZ incubation diminished these amounts. However, their amounts were additionally increased in the LPS than in the control. LPS-induced increases of cell viability were diminished in the control and LPS groups by the CAPZ.
In summary, CAPZ treatment through TRPV1 inhibition contributes to the oxidative stress and apoptosis that LPS causes in ARPE-19 cells. TRPV1 inhibition by CAPZ may be a viable treatment option for oxidative retinal damage induced by LPS.
Ethical Statement
No data of animals and human.
Supporting Institution
BSN Health, Analyses, Innov., Consult., Org., Agricul., Trade Ltd. (Göller Bölgesi Teknokenti, Isparta, Türkiye)
Thanks
Muhammet Şahin, a technician, assisted with plate reader analyses, for which the authors are grateful.
References
- Ahmed CM, Patel AP, Johnson HM, Ildefonso CJ, Lewin AS. (2023) Suppressor of cytokine signaling 3-derived peptide as a therapeutic for inflammatory and oxidative stress-induced damage to the retina. Mol Vis. 29:338-356.
- Bok E, Chung YC, Kim KS, Baik HH, Shin WH, Jin BK. (2018) Modulation of M1/M2 polarization by capsaicin contributes to the survival of dopaminergic neurons in the lipopolysaccharide-lesioned substantia nigra in vivo. Exp Mol Med. 50(7):1-14. https://doi.org/10.1038/s12276-018-0111-4.
- Caroff M, Karibian D. (2003) Structure of bacterial lipopolysaccharides. Carbohydr Res. 338(23):2431-47. https://doi.org/10.1016/j.carres.2003.07.010.
- Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389(6653): 816-824. https://doi.org/10.1038/39807.
- Chistyakov DV, Tiulina VV, Gancharova OS, et al. (2024) Targeting Oxidative Stress and Inflammation in the Eye: Insights from a New Model of Experimental Autoimmune Uveitis. Int J Mol Sci. 25(23):12910. https://doi.org/10.3390/ijms252312910.
- Chuang HH, Lin S. (2009) Oxidative challenges sensitize the capsaicin receptor by covalent cysteine modification. Proc Natl Acad Sci U S A. 106(47):20097-102. https://doi.org/10.1073/pnas.0902675106.
- Cordeiro S, Seyler S, Stindl J, Milenkovic VM, Strauss O. (2010) Heat-sensitive TRPV channels in retinal pigment epithelial cells: regulation of VEGF-A secretion. Invest Ophthalmol Vis Sci. 51(11):6001-6008. https://doi.org/10.1167/iovs.09-4720.
- Daldal H, Nazıroğlu M. (2022) Rituximab Attenuated Lipopolysaccharide-Induced Oxidative Cytotoxicity, Apoptosis, and Inflammation in the Human Retina Cells via Modulating the TRPM2 Signaling Pathways. Ocul Immunol Inflamm. 30(6):1315-1328. https://doi.org/10.1080/09273948.2022.2075400.
- Ertuğrul A, Özkaya D, Nazıroğlu M. (2023) Curcumin attenuates hydroxychloroquine-mediated apoptosis and oxidative stress via the inhibition of TRPM2 channel signalling pathways in a retinal pigment epithelium cell line. Graefes Arch Clin Exp Ophthalmol. 2023 Oct;261(10):2829-2844. https://doi.org/10.1007/s00417-023-06082-5.
- Freitas HR, Isaac AR, Silva TM, et al. (2019) Cannabinoids Induce Cell Death and Promote P2X7 Receptor Signaling in Retinal Glial Progenitors in Culture. Mol Neurobiol 56(9):6472-6486. https://doi.org/10.1007/s12035-019-1537-y.
- Güzel M, Akpınar O. (2021) Hydroxychloroquine Attenuates Acute Inflammation (LPS)-Induced Apoptosis via Inhibiting TRPV1 Channel/ROS Signaling Pathways in Human Monocytes. Biology (Basel). 10(10):967. https://doi.org/10.3390/biology10100967.
- Han D, Wu X, Liu L, Shu W, Huang Z. (2018) Sodium tanshinone IIA sulfonate protects ARPE-19 cells against oxidative stress by inhibiting autophagy and apoptosis. Sci Rep. 8(1):15137. https://doi.org/10.1038/s41598-018-33552-2.
- Han J, Wu J, Liu H, et al. (2023) Inhibition of pyroptosis and apoptosis by capsaicin protects against LPS-induced acute kidney injury through TRPV1/UCP2 axis in vitro. Open Life Sci. 18(1):20220647. https://doi.org/10.1515/biol-2022-0647.
- Hayashi H, Eguchi Y, Fukuchi-Nakaishi Y, et al. (2012) A potential neuroprotective role of apolipoprotein E-containing lipoproteins through low density lipoprotein receptor-related protein 1 in normal tension glaucoma. J Biol Chem. 287(30):25395-406. https://doi.org/10.1074/jbc.M112.370130.
- Hu Y, Chen G, Huang J, et al. (2021) The Calcium Channel Inhibitor Nimodipine Shapes the Uveitogenic T Cells and Protects Mice from Experimental Autoimmune Uveitis through the p38-MAPK Signaling Pathway. J Immunol. 207(12):2933-2943. https://doi.org/10.4049/jimmunol.2100568.
- Kievit B, Johnstone AD, Gibon J, Barker PA. (2022) Mitochondrial Reactive Oxygen Species Mediate Activation of TRPV1 and Calcium Entry Following Peripheral Sensory Axotomy. Front Mol Neurosci. 18;15:852181. https://doi.org/10.3389/fnmol.2022.852181.
- Laorob T, Ngoenkam J, Nuiyen A, et al. (2024) Comparative effectiveness of nitro dihydrocapsaicin, new synthetic derivative capsaicinoid, and capsaicin in alleviating oxidative stress and inflammation on lipopolysaccharide-stimulated corneal epithelial cells. Exp Eye Res. 244:109950. https://doi.org/10.1016/j.exer.2024.109950.
- Leonelli M, Martins DO, Britto LR. (2013) Retinal cell death induced by TRPV1 activation involves NMDA signaling and upregulation of nitric oxide synthases. Cell Mol Neurobiol. 33(3):379-392. https://doi.org/10.1007/s10571-012-9904-5.
- Meléndez García R, Arredondo Zamarripa D, Arnold E, et al., (2016). Prolactin protects retinal pigment epithelium by inhibiting sirtuin 2-dependent cell death. EBioMedicine. 7:35-49. https://doi.org/10.1016/j.ebiom.2016.03.048.
- Murakami Y, Ishikawa K, Nakao S, Sonoda KH. (2020) Innate immune response in retinal homeostasis and inflammatory disorders. Prog Retin Eye Res. 74:100778. https://doi.org/10.1016/j.preteyeres.2019.100778.
- Ozal SA, Turkekul K, Gurlu V, Guclu H, Erdogan S. (2018) Esculetin Protects Human Retinal Pigment Epithelial Cells from Lipopolysaccharide-induced Inflammation and Cell Death. Curr Eye Res. 43(9):1169-1176. https://doi.org/10.1080/02713683.2018.1481517.
- Özkaya D, Nazıroğlu M, Vanyorek L, Muhamad S. (2021) Involvement of TRPM2 Channel on Hypoxia-Induced Oxidative Injury, Inflammation, and Cell Death in Retinal Pigment Epithelial Cells: Modulator Action of Selenium Nanoparticles. Biol Trace Elem Res. 199(4):1356-1369. https://doi.org/10.1007/s12011-020-02556-3.
- Saddala MS, Lennikov A, Mukwaya A, Yang Y, Hill MA, Lagali N, Huang H. (2020) Discovery of novel L-type voltage-gated calcium channel blockers and application for the prevention of inflammation and angiogenesis. J Neuroinflammation. 17(1):132. https://doi.org/10.1186/s12974-020-01801-9.
- Sappington RM, Sidorova T, Long DJ, Calkins DJ. (2009) TRPV1: contribution to retinal ganglion cell apoptosis and increased intracellular Ca2+ with exposure to hydrostatic pressure. Invest Ophthalmol Vis Sci. 50(2):717-728. https://doi.org/10.1167/iovs.08-2321.
- Sappington RM, Sidorova T, Ward NJ, Chakravarthy R, Ho KW, Calkins DJ. (2015) Activation of transient receptor potential vanilloid-1 (TRPV1) influences how retinal ganglion cell neurons respond to pressure-related stress. Channels (Austin). 9(2):102-113. https://doi.org/10.1080/19336950.2015.1009272.
- Souza Monteiro de Araújo D, De Logu F, Adembri C, et al. (2020) TRPA1 mediates damage of the retina induced by ischemia and reperfusion in mice. Cell Death Dis.;11(8):633. https://doi.org/10.1038/s41419-020-02863-6.
- Srejovic JV, Muric MD, Jakovljevic VL, et al. (2024) Molecular and Cellular Mechanisms Involved in the Pathophysiology of Retinal Vascular Disease-Interplay Between Inflammation and Oxidative Stress. Int J Mol Sci. 25(21):11850. https://doi.org/10.3390/ijms252111850.
- Tang M, Liu W. (2024) Tropisetron attenuates high glucose-induced oxidative stress and inflammation in ARPE-19 cells in vitro via regulating SIRT1/ROCK1 signaling. Drug Dev Res. 85(7):e70002. https://doi.org/10.1002/ddr.70002.
- Vaglienti MV, Subirada PV, Barcelona PF, Bonacci G, Sanchez MC. (2022) Quantification of Reactive Oxygen Species Using 2',7'-Dichlorofluorescein Diacetate Probe and Flow-Cytometry in Müller Glial Cells. J Vis Exp. (183). https://doi.org/10.3791/63337.
- Wang K, Zhu X, Zhang K, Yao Y, Zhuang M, Tan C, Zhou F, Zhu L. (2017) Puerarin inhibits amyloid β-induced NLRP3 inflammasome activation in retinal pigment epithelial cells via suppressing ROS-dependent oxidative and endoplasmic reticulum stresses. Exp Cell Res. 357(2):335-340. https://doi.org/10.1016/j.yexcr.2017.05.030.
- Yu M, Tian H, Lu R, Quan N, Qian L. (2024) TRPV1 Promotes Periodontitis Tissue Inflammation and Oxidative Damage by Regulating STAT3 Signaling Pathway. J Periodontal Res. 2024 Dec 1. https://doi.org/10.1111/jre.13368. Epub ahead of print.
- Zhang M, Wang L, Wen D, et al., (2021) Neuroprotection of retinal cells by Caffeic Acid Phenylethyl Ester(CAPE) is mediated by mitochondrial uncoupling protein UCP2. Neurochem Int. 151:105214. https://doi.org/10.1016/j.neuint.2021.105214.
- Zhang Z, Shan X, Li S, et al. (2024) Retinal light damage: From mechanisms to protective strategies. Surv Ophthalmol. 69(6):905-915. https://doi.org/10.1016/j.survophthal.2024.07.004.