Protective effect of saffron carotenoids against amyloid beta-induced neurotoxicity in differentiated PC12 cells via the unfolded protein response and autophagy.
AD
AβOs
UPR
autophagy
crocetin
crocin
Journal
Phytotherapy research : PTR
ISSN: 1099-1573
Titre abrégé: Phytother Res
Pays: England
ID NLM: 8904486
Informations de publication
Date de publication:
15 Feb 2023
15 Feb 2023
Historique:
revised:
12
01
2023
received:
03
04
2022
accepted:
29
01
2023
pubmed:
17
2
2023
medline:
17
2
2023
entrez:
16
2
2023
Statut:
aheadofprint
Résumé
The preventive effect of saffron against Alzheimer's disease (AD) has been reported. Herein, we studied the effect of Cro and Crt, saffron carotenoids, on the cellular model of AD. The MTT assay, flow cytometry, and elevated p-JNK, p-Bcl-2, and c-PARP indicated the AβOs-induced apoptosis in differentiated PC12 cells. Then, the protective effects of Cro/Crt on dPC12 cells against AβOs were investigated in preventive and therapeutic modalities. Starvation was used as a positive control. RT-PCR and Western blot results revealed the reduced eIF2α phosphorylation and increased spliced-XBP1, Beclin1, LC3II, and p62, which indicate the AβOs-induced autophagic flux defect, autophagosome accumulation, and apoptosis. Cro and Crt inhibited the JNK-Bcl-2-Beclin1 pathway. They altered Beclin1 and LC3II and decreased p62 expressions, leading cells to survival. Cro and Crt altered the autophagic flux by different mechanisms. So, Cro increased the rate of autophagosome degradation more than Crt, while Crt increased the rate of autophagosome formation more than Cro. The application of 4μ8C and chloroquine as the inhibitors of XBP1 and autophagy, respectively, confirmed these results. So, augmentation of the survival branches of UPR and autophagy is involved and may serve as an effective strategy to prevent the progression of AβOs toxicity.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : key projects of international scientific and technological innovation cooperation between governments
ID : 2017YFE0130100
Organisme : Tarbiat Modares University
ID : IG-39807
Organisme : Zhejiang University of Technology
ID : 2022C03050
Organisme : Tarbiat Modares University
ID : Med-75113
Informations de copyright
© 2023 John Wiley & Sons Ltd.
Références
Asadi, F., Jamshidi, A. H., Khodagholi, F., Yans, A., Azimi, L., Faizi, M., Vali, L., Abdollahi, M., Ghahremani, M. H., & Sharifzadeh, M. (2015). Reversal effects of crocin on amyloid beta-induced memory deficit: Modification of autophagy or apoptosis markers. Pharmacology, Biochemistry, and Behavior, 139, 47-58. https://doi.org/10.1016/j.pbb.2015.10.011
Asdaq, S. M. B., & Inamdar, M. N. (2010). Potential of Crocus sativus (saffron) and its constituent, crocin, as hypolipidemic and antioxidant in rats. Applied Biochemistry and Biotechnology, 162(2), 358-372.
Association, A. s. (2019). 2019 Alzheimer's disease facts and figures. Alzheimer's & Dementia, 15(3), 321-387.
B'chir, W., Maurin, A.-C., Carraro, V., Averous, J., Jousse, C., Muranishi, Y., Parry, L., Stepien, G., Fafournoux, P., & Bruhat, A. (2013). The eIF2α/ATF4 pathway is essential for stress-induced autophagy gene expression. Nucleic Acids Research, 41(16), 7683-7699.
Bathaie, S. Z., Farajzade, A., & Hoshyar, R. (2014). A review of the chemistry and uses of crocins and crocetin, the carotenoid natural dyes in saffron, with particular emphasis on applications as colorants including their use as biological stains. Biotechnic & Histochemistry, 89(6), 401-411.
Bathaie, S. Z., & Mousavi, S. Z. (2010). New applications and mechanisms of action of saffron and its important ingredients. Critical Reviews in Food Science and Nutrition, 50(8), 761-786.
Bernales, S., McDonald, K. L., & Walter, P. (2006). Autophagy counterbalances endoplasmic reticulum expansion during the unfolded protein response. PLoS Biology, 4(12), e423.
Bjørkøy, G., Lamark, T., Pankiv, S., Øvervatn, A., Brech, A., & Johansen, T. (2009). Monitoring autophagic degradation of p62/SQSTM1. Methods in Enzymology, 452, 181-197.
Boland, B., Yu, W. H., Corti, O., Mollereau, B., Henriques, A., Bezard, E., Pastores, G. M., Rubinsztein, D. C., Nixon, R. A., Duchen, M. R., Mallucci, G. R., Kroemer, G., Levine, B., Eskelinen, E.-L., Mochel, F., Spedding, M., Louis, C., Martin, O. R., & Duchen, M. R. (2018). Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing. Nature Reviews Drug Discovery, 17(9), 660-688.
Bradford, M. M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry, 72(1-2), 248-254.
Cai, Y., Arikkath, J., Yang, L., Guo, M.-L., Periyasamy, P., & Buch, S. (2016). Interplay of endoplasmic reticulum stress and autophagy in neurodegenerative disorders. Autophagy, 12(2), 225-244.
Canevari, L., Abramov, A. Y., & Duchen, M. R. (2004). Toxicity of amyloid β peptide: Tales of calcium, mitochondria, and oxidative stress. Neurochemical Research, 29(3), 637-650.
Chafekar, S. M., Hoozemans, J. J., Zwart, R., Baas, F., & Scheper, W. (2007). Aβ1-42Induces mild endoplasmic reticulum stress in an aggregation state-dependent manner. Antioxidants & Redox Signaling, 9(12), 2245-2254.
Chalatsa, I., Arvanitis, D. A., Koulakiotis, N. S., Giagini, A., Skaltsounis, A. L., Papadopoulou-Daifoti, Z., Tsarbopoulos, A., & Sanoudou, D. (2019). The Crocus sativus compounds trans-crocin 4 and trans-crocetin modulate the amyloidogenic pathway and tau misprocessing in Alzheimer disease neuronal cell culture models. Frontiers in Neuroscience, 13, 249.
Chifenti, B., Locci, M. T., Lazzeri, G., Guagnozzi, M., Dinucci, D., Chiellini, F., Filice, M. E., Salerno, M. G., & Battini, L. (2013). Autophagy-related protein LC3 and Beclin-1 in the first trimester of pregnancy. Clinical and Experimental Reproductive Medicine, 40(1), 33-37. https://doi.org/10.5653/cerm.2013.40.1.33
Chomczynski, P., & Sacchi, N. (1987). Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Analytical Biochemistry, 162(1), 156-159.
Costa, C. A. D., Manaa, W. E., Duplan, E., & Checler, F. (2020). The endoplasmic reticulum stress/unfolded protein response and their contributions to Parkinson's disease physiopathology. Cell, 9(11), 2495.
Cui, J., Zhang, M., Zhang, Y.-Q., & Xu, Z.-H. (2007). JNK pathway: Diseases and therapeutic potential. Acta Pharmacologica Sinica, 28(5), 601-608.
Das, K. P., Freudenrich, T. M., & Mundy, W. R. (2004). Assessment of PC12 cell differentiation and neurite growth: A comparison of morphological and neurochemical measures. Neurotoxicology and Teratology, 26(3), 397-406.
Ebrahimi, S. M., Bathaie, S. Z., Faridi, N., Taghikhani, M., Nakhjavani, M., & Faghihzadeh, S. (2019). L-lysine protects C2C12 myotubes and 3T3-L1 adipocytes against high glucose damages and stresses. PLoS One, 14(12), e0225912.
Finley, J. W., & Gao, S. (2017). A perspective on Crocus sativus L.(saffron) constituent crocin: A potent water-soluble antioxidant and potential therapy for Alzheimer's disease. Journal of Agricultural and Food Chemistry, 65(5), 1005-1020.
Ghahghaei, A., Bathaie, S. Z., & Bahraminejad, E. (2012). Mechanisms of the effects of crocin on aggregation and deposition of a beta 1-40 fibrils in Alzheimer's disease. International Journal of Peptide Research and Therapeutics, 18(4), 347-351. https://doi.org/10.1007/s10989-012-9308-x
Ghahghaei, A., Bathaie, S. Z., Kheirkhah, H., & Bahraminejad, E. (2013). The protective effect of crocin on the amyloid fibril formation of a beta 42 peptide in vitro. Cellular & Molecular Biology Letters, 18(3), 328-339. https://doi.org/10.2478/s11658-013-0092-1
Harris, H., & Rubinsztein, D. C. (2012). Control of autophagy as a therapy for neurodegenerative disease. Nature Reviews Neurology, 8(2), 108-117.
Hashemi, S. A., Bathaie, S. Z., & Mohagheghi, M. A. (2020). Interaction of saffron carotenoids with catalase: In vitro, in vivo and molecular docking studies. Journal of Biomolecular Structure & Dynamics, 38(13), 3916-3926. https://doi.org/10.1080/07391102.2019.1668302
Hashemi, S. A., Karami, M., & Bathaie, S. Z. (2020). Saffron carotenoids change the superoxide dismutase activity in breast cancer: In vitro, in vivo and in silico studies. International Journal of Biological Macromolecules, 158, 845-853. https://doi.org/10.1016/j.ijbiomac.2020.04.063
Hayashi-Nishino, M., Fujita, N., Noda, T., Yamaguchi, A., Yoshimori, T., & Yamamoto, A. (2009). A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formation. Nature Cell Biology, 11(12), 1433-1437.
Hetz, C., & Saxena, S. (2017). ER stress and the unfolded protein response in neurodegeneration. Nature Reviews Neurology, 13(8), 477-491.
Jnaneshwari, S., Hemshekhar, M., Santhosh, M. S., Sunitha, K., Thushara, R., Thirunavukkarasu, C., Kemparaju, K., & Girish, K. S. (2013). Crocin, a dietary colorant mitigates cyclophosphamide-induced organ toxicity by modulating antioxidant status and inflammatory cytokines. Journal of Pharmacy and Pharmacology, 65(4), 604-614.
Kabir, M. F., Kim, H.-R., & Chae, H.-J. (2018). Endoplasmic reticulum stress and autophagy. Endoplasmic Reticulum.
Kandimalla, K. K., Scott, O. G., Fulzele, S., Davidson, M. W., & Poduslo, J. F. (2009). Mechanism of neuronal versus endothelial cell uptake of Alzheimer's disease amyloid β protein. PLoS One, 4(2), e4627.
Kishino, A., Hayashi, K., Hidai, C., Masuda, T., Nomura, Y., & Oshima, T. (2017). XBP1-FoxO1 interaction regulates ER stress-induced autophagy in auditory cells. Scientific Reports, 7(1), 4442. https://doi.org/10.1038/s41598-017-02960-1
Lee, D. Y., Lee, K.-S., Lee, H. J., Kim, D. H., Noh, Y. H., Yu, K., Yu, K., Jung, H.-Y., Lee, S. H., Lee, J. Y., Youn, Y. C., Jeong, Y., Kim, D. K., Lee, W. B., & Youn, Y. C. (2010). Activation of PERK signaling attenuates Aβ-mediated ER stress. PLoS One, 5(5), e10489.
Lee, J. H., Won, S. M., Suh, J., Son, S. J., Moon, G. J., Park, U.-J., & Gwag, B. J. (2010). Induction of the unfolded protein response and cell death pathway in Alzheimer's disease, but not in aged Tg2576 mice. Experimental & Molecular Medicine, 42(5), 386-394.
Ma, J. F., Huang, Y., Chen, S. D., & Halliday, G. (2010). Immunohistochemical evidence for macroautophagy in neurones and endothelial cells in Alzheimer's disease. Neuropathology and Applied Neurobiology, 36(4), 312-319.
Maiuri, M. C., Criollo, A., Tasdemir, E., Vicencio, J. M., Tajeddine, N., Hickman, J. A., Geneste, O., & Kroemer, G. (2007). BH3-only proteins and BH3 mimetics induce autophagy by competitively disrupting the interaction between Beclin 1 and Bcl-2/Bcl-XL. Autophagy, 3(4), 374-376.
Mao, K., & Zhang, G. (2021). The role of PARP1 in neurodegenerative diseases and aging. The FEBS Journal, 289, 2013-2024. https://doi.org/10.1111/febs.15716
Mauthe, M., Orhon, I., Rocchi, C., Zhou, X., Luhr, M., Hijlkema, K. J., Coppes, R. P., Engedal, N., Mari, M., & Reggiori, F. (2018). Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion. Autophagy, 14(8), 1435-1455. https://doi.org/10.1080/15548627.2018.1474314
Menon, M. B., & Dhamija, S. (2018). Beclin 1 phosphorylation-at the center of autophagy regulation. Frontiers in Cell and Development Biology, 6, 137.
Morris, G., Walker, A. J., Berk, M., Maes, M., & Puri, B. K. (2018). Cell death pathways: A novel therapeutic approach for neuroscientists. Molecular Neurobiology, 55(7), 5767-5786. https://doi.org/10.1007/s12035-017-0793-y
Mousavi, B., Bathaie, S. Z., Fadai, F., Ashtari, Z., Farhang, S., Hashempour, S., Shahhamzei, N., & Heidarzadeh, H. (2015). Safety evaluation of saffron stigma (Crocus sativus L.) aqueous extract and crocin in patients with schizophrenia. Avicenna Journal of Phytomedicine, 5(5), 413.
Mousavi, S. Z., & Bathaie, S. Z. (2011). Historical uses of saffron: Identifying potential new avenues for modern research. Avicenna Journal of Phytomedicine, 1(2), 57-66.
Mudher, A., Chapman, S., Richardson, J., Asuni, A., Gibb, G., Pollard, C., Killick, R., Iqbal, T., Raymond, L., Varndell, I., Sheppard, P., Makoff, A., Gower, E., Soden, P. E., Lewis, P., Murphy, M., Golde, T. E., Rupniak, H. T., Anderton, B. H., & Varndell, I. (2001). Dishevelled regulates the metabolism of amyloid precursor protein via protein kinase C/mitogen-activated protein kinase and c-Jun terminal kinase. Journal of Neuroscience, 21(14), 4987-4995.
Nam, K. N., Park, Y.-M., Jung, H.-J., Lee, J. Y., Min, B. D., Park, S.-U., Jung, W.-S., Cho, K.-H., Park, J.-H., Kang, I., Hong, J.-W., & Kang, I. (2010). Anti-inflammatory effects of crocin and crocetin in rat brain microglial cells. European Journal of Pharmacology, 648(1-3), 110-116.
Nasimian, A., Farzaneh, P., Tamanoi, F., & Bathaie, S. Z. (2020). Cytosolic and mitochondrial ROS production resulted in apoptosis induction in breast cancer cells treated with crocin: The role of FOXO3a, PTEN and AKT signaling. Biochemical Pharmacology, 177, 113999.
Oakes, S. A., & Papa, F. R. (2015). The role of endoplasmic reticulum stress in human pathology. Annual Review of Pathology: Mechanisms of Disease, 10, 173-194.
Ohno, M. (2018). PERK as a hub of multiple pathogenic pathways leading to memory deficits and neurodegeneration in Alzheimer's disease. Brain Research Bulletin, 141, 72-78.
Okazawa, H., & Estus, S. (2002). The JNK/c-Jun cascade and Alzheimer's disease. American Journal of Alzheimer's Disease and Other Dementias, 17(2), 79-88.
Papandreou, M. A., Kanakis, C. D., Polissiou, M. G., Efthimiopoulos, S., Cordopatis, P., Margarity, M., & Lamari, F. N. (2006). Inhibitory activity on amyloid-β aggregation and antioxidant properties of Crocus sativus stigmas extract and its crocin constituents. Journal of Agricultural and Food Chemistry, 54(23), 8762-8768.
Papandreou, M. A., Tsachaki, M., Efthimiopoulos, S., Cordopatis, P., Lamari, F. N., & Margarity, M. (2011). Memory enhancing effects of saffron in aged mice are correlated with antioxidant protection. Behavioural Brain Research, 219(2), 197-204.
Peñaranda-Fajardo, N. M., Meijer, C., Liang, Y., Dijkstra, B. M., Aguirre-Gamboa, R., den Dunnen, W. F., & Kruyt, F. A. (2019). ER stress and UPR activation in glioblastoma: Identification of a noncanonical PERK mechanism regulating GBM stem cells through SOX2 modulation. Cell Death & Disease, 10(10), 1-16.
Qiu, C., Wang, Y.-P., Pan, X.-D., Liu, X.-Y., Chen, Z., & Liu, L.-B. (2016). Exendin-4 protects Aβ (1-42) oligomer-induced PC12 cell apoptosis. American Journal of Translational Research, 8(8), 3540.
Ren, H., Zhai, W., Lu, X., & Wang, G. (2021). The cross-links of endoplasmic reticulum stress, autophagy, and neurodegeneration in parkinson's disease. Frontiers in Aging Neuroscience, 13, 691881.
Rubinsztein, D. C., Cuervo, A. M., Ravikumar, B., Sarkar, S., Korolchuk, V. I., Kaushik, S., & Klionsky, D. J. (2009). In search of an “autophagomometer”. Taylor & Francis.
Seneci, P. (2014). Protein Misfolding, Neurodegeneration and Tau. In Molecular targets in protein misfolding and neurodegenerative disease. Academic Press.
Stine, W. B., Jungbauer, L., Yu, C., & LaDu, M. J. (2010). Preparing synthetic Aβ in different aggregation states. In Alzheimer's disease and frontotemporal dementia (pp. 13-32). Springer.
Taheri, F., Bathaie, S. Z., Ashrafi, M., & Ghasemi, E. (2014). Assessment of crocin toxicity on the rat liver. Pathobiology Research, 17(3), 67-79.
Tran, S., Fairlie, W. D., & Lee, E. F. (2021). BECLIN1: Protein structure, function and regulation. Cell, 10(6), 1522.
Urano, F., Wang, X. Z., Bertolotti, A., Zhang, Y., Chung, P., Harding, H. P., & Ron, D. (2000). Coupling of Stress in the ER to Activation of JNK Protein Kinases by Transmembrane Protein Kinase IRE1. Science, 287, 664-666. https://www.science.org/doi/epdf/10.1126/science.287.5453.664
Van Meerloo, J., Kaspers, G. J., & Cloos, J. (2011). Cell sensitivity assays: The MTT assay. In Cancer cell culture (pp. 237-245). Springer.
Verschooten, L., Barrette, K., Van Kelst, S., Rubio Romero, N., Proby, C., De Vos, R., Agostinis, P., & Garmyn, M. (2012). Autophagy inhibitor chloroquine enhanced the cell death inducing effect of the flavonoid luteolin in metastatic squamous cell carcinoma cells. PLoS One, 7(10), e48264. https://doi.org/10.1371/journal.pone.0048264
Walter, P., & Ron, D. (2011). The unfolded protein response: From stress pathway to homeostatic regulation. Science, 334(6059), 1081-1086.
Wang, M., & Kaufman, R. J. (2016). Protein misfolding in the endoplasmic reticulum as a conduit to human disease. Nature, 529(7586), 326-335.
Wani, A., Al Rihani, S. B., Sharma, A., Weadick, B., Govindarajan, R., Khan, S. U., Sharma, P. R., Dogra, A., Nandi, U., Reddy, C. N., Bharate, S. S., Singh, G., Bharate, S. B., Vishwakarma, R. A., Kaddoumi, A., & Reddy, C. N. (2021). Crocetin promotes clearance of amyloid-β by inducing autophagy via the STK11/LKB1-mediated AMPK pathway. Autophagy, 17, 3813-3832.
Wencel, P. L., Lukiw, W. J., Strosznajder, J. B., & Strosznajder, R. P. (2018). Inhibition of poly (ADP-ribose) polymerase-1 enhances gene expression of selected sirtuins and APP cleaving enzymes in amyloid beta cytotoxicity. Molecular Neurobiology, 55(6), 4612-4623.
Wiatrak, B., Kubis-Kubiak, A., Piwowar, A., & Barg, E. (2020). PC12 cell line: Cell types, coating of culture vessels, differentiation and other culture conditions. Cell, 9(4), 958. https://doi.org/10.3390/cells9040958
Yao, M., Nguyen, T.-V. V., & Pike, C. J. (2005). β-Amyloid-induced neuronal apoptosis involves c-Jun N-terminal kinase-dependent downregulation of Bcl-w. Journal of Neuroscience, 25(5), 1149-1158.
Zhi-Kun, S., Hong-Qi, Y., Zhi-Quan, W., Jing, P., Zhen, H., & Sheng-Di, C. (2012). Erythropoietin prevents PC12 cells from beta-amyloid-induced apoptosis via PI3K/Akt pathway. Translational Neurodegeneration, 1(1), 1-9.
Zhu, X.-C., Yu, J.-T., Jiang, T., & Tan, L. (2013). Autophagy modulation for Alzheimer's disease therapy. Molecular Neurobiology, 48(3), 702-714.