Effect of High Cholesterol Diet and α-Tocopherol Supplementation on Endoplasmic Retüculum Stress and Apoptosis in Hippocampus Tissue

Yıl 2022, Cilt: 12 Sayı: 2, 439 - 444, 30.06.2022

Erdi Sozen Tugce Demırel-yalcıner Aslı Ece Alper Ismıcoglu Nesrin Kartal Özer

https://doi.org/10.33808/clinexphealthsci.972222

Öz

Objective: Neurodegenerative diseases are life-threatening disorders that occur when cells in peripheral nervous system or brain lose function over time and ultimately die. Our study aimed to establish a high cholesterol fed rabbit model to investigate the status of endoplasmic reticulum (ER) stress, proteasome activity and apoptosis as well as the beneficial role of α-tocopherol on hippocampus.

Methods: Hypercholesterolemic rabbit model was established by feeding on 2% cholesterol diet for 8 weeks, and α-tocopherol supplementation was applied with intramuscular injections. Alterations of Grp78, Grp94, Bax, Bcl-2 and BACE1 levels in hippocampus tissue were determined by western blotting, while proteasome activity was measured by fluorometric detection.

Results: Cholesterol containing diet for 8 weeks increased well-known parameters of ER stress and apoptosis, together with no chance in proteasome activity. On the other hand, α-tocopherol supplementation in rabbits fed two percent cholesterol containing diet significantly down-regulated certain ER stress and apoptosis parameters along with an increase in proteasome activity.
Conclusion: Our results underline a novel function of α-tocopherol in reducing cholesterol induced ER stress and apoptosis by increasing proteasome activity in the hippocampus.

Anahtar Kelimeler

Hypercholesterolemia, Endoplasmic reticulum stress, Proteasome, Apoptosis, Hippocampus

Kaynakça

• [1] Lee D, Choi YH, Seo J, Kim JK, Lee SB. Discovery of new epigenomics-based biomarkers and the early diagnosis of neurodegenerative diseases. Ageing Res Rev. 2020;61:101069.
• [2] Chong AJ, Lim SW, Lee YL, Chio CC, Chang CH, Kuo JR. The Neuroprotective effects of simvastatin on high cholesterol following traumatic brain injury in rats. World Neurosurg. 2019;132:e99-e108.
• [3] Sparks DL, Kuo YM, Roher A, Martin T, Lukas RJ. Alterations of Alzheimer’s disease in the cholesterol-fed rabbit, including vascular inflammation. Preliminary observations. Ann N Y Acad Sci. 2000;903:335-344.
• [4] Refolo LM, Malester B, LaFrancois J, Bryant-Thomas T, Wang R, Tint GS. Hypercholesterolemia accelerates the Alzheimer’s amyloid pathology in a transgenic mouse model. Neurobiol Dis. 2000;7(4):321-331.
• [5] Levin-Allerhand JA, Lominska CE, Smith JD. Increased amyloid – levels in APPSWE transgenic mice treated chronically with a physiological high-fat high-cholesterol diet. J Nutr Health Aging. 2002;6(5):315-319.
• [6] Hottman DA, Chernick D, Cheng S, Wang Z, Li L. HDL and cognition in neurodegenerative disorders. Neurobiol Dis. 2014;72 Pt A:22-36.
• [7] Popp J, Meichsner S, Kolsch H, Lewczuk P, Maier W, Kornhuber J. Cerebral and extracerebral cholesterol metabolism and CSF markers of Alzheimer’s disease. Biochem Pharmacol. 2013;86(1):37-42.
• [8] Sozen E, Ozer NK. Impact of high cholesterol and endoplasmic reticulum stress on metabolic diseases: An updated minireview. Redox Biol. 2017;12:456-461.
• [9] Xiang C, Wang Y, Zhang H, Han F. The role of endoplasmic reticulum stress in neurodegenerative disease. Apoptosis. 2017;22(1):1-26.
• [10] Lindholm D, Wootz H, Korhonen L. ER stress and neurodegenerative diseases. Cell Death Differ. 2006;13(3):385- 392.
• [11] Thibaudeau TA, Anderson RT, Smith DM. A common mechanism of proteasome impairment by neurodegenerative disease-associated oligomers. Nat Commun. 2018;9(1):1097.
• [12] De Strooper B. Proteases and proteolysis in Alzheimer disease: a multifactorial view on the disease process. Physiol Rev. 2010;90(2):465-494.
• [13] Salminen A, Kauppinen A, Suuronen T, Kaarniranta K, Ojala J. ER stress in Alzheimer’s disease: a novel neuronal trigger for inflammation and Alzheimer’s pathology. J Neuroinflammation. 2009;6:41.
• [14] Zhao XS, Wu Q, Peng J, Pan LH, Ren Z, Liu HT. Hyperlipidemiainduced apoptosis of hippocampal neurons in apoE(-/-) mice may be associated with increased PCSK9 expression. Mol Med Rep. 2017;15(2):712-718.
• [15] Icer MA, Arslan N, Gezmen-Karadag M. Effects of vitamin E on neurodegenerative diseases: an update. Acta Neurobiol Exp (Wars). 2021;81(1):21-33.
• [16] Miyake Y, Tanaka K, Fukushima W, Sasaki S, Kiyohara C, Tsuboi Y. Dietary intake of metals and risk of Parkinson’s disease: a case-control study in Japan. J Neurol Sci. 2011;306(1-2):98- 102.
• [17] Hughes KC, Gao X, Kim IY, Rimm EB, Wang M, Weisskopf MG. Intake of antioxidant vitamins and risk of Parkinson’s disease. Mov Disord. 2016;31(12):1909-1914.
• [18] Yang F, Wolk A, Hakansson N, Pedersen NL, Wirdefeldt K. Dietary antioxidants and risk of Parkinson’s disease in two population-based cohorts. Mov Disord. 2017;32(11):1631- 1636.
• [19] Ambrogini P, Minelli A, Galati C, Betti M, Lattanzi D, Ciffolilli S. Post-seizure alpha-tocopherol treatment decreases neuroinflammation and neuronal degeneration induced by status epilepticus in rat hippocampus. Mol Neurobiol. 2014;50(1):246-256.
• [20] Wang WY, Tan MS, Yu JT, Tan L. Role of pro-inflammatory cytokines released from microglia in Alzheimer’s disease. Ann Transl Med. 2015;3(10):136.
• [21] Galli F, Azzi A, Birringer M, Cook-Mills JM, Eggersdorfer M, Frank J. Vitamin E: Emerging aspects and new directions. Free Radic Biol Med. 2017;102:16-36.
• [22] Sirikci O, Ozer NK, Azzi A. Dietary cholesterol-induced changes of protein kinase C and the effect of vitamin E in rabbit aortic smooth muscle cells. Atherosclerosis. 1996;126(2):253-263.
• [23] Sozen E, Karademir B, Yazgan B, Bozaykut P, Ozer NK. Potential role of proteasome on c-jun related signaling in hypercholesterolemia induced atherosclerosis. Redox Biol. 2014;2:732-738.
• [24] Nierenberg DW, Nann SL. A method for determining concentrations of retinol, tocopherol, and five carotenoids in human plasma and tissue samples. Am J Clin Nutr. 1992;56(2):417-426.
• [25] Sozen E, Karademir B, Ozer NK. Basic mechanisms in endoplasmic reticulum stress and relation to cardiovascular diseases. Free Radic Biol Med. 2015;78:30-41.
• [26] Wang Q, Zhang L, Yuan X, Ou Y, Zhu X, Cheng Z. The Relationship between the Bcl-2/Bax Proteins and the MitochondriaMediated Apoptosis Pathway in the Differentiation of Adipose-Derived Stromal Cells into Neurons. PLoS One. 2016;11(10):e0163327.
• [27] Brooks SW, Dykes AC, Schreurs BG. A high-cholesterol diet increases 27-hydroxycholesterol and modifies estrogen receptor expression and neurodegeneration in rabbit hippocampus. J Alzheimers Dis. 2017;56(1):185-196.
• [28] Ghribi O, Larsen B, Schrag M, Herman MM. High cholesterol content in neurons increases BACE, beta-amyloid, and phosphorylated tau levels in rabbit hippocampus. Exp Neurol. 2006;200(2):460-467.
• [29] Jaya Prasanthi RP, Schommer E, Thomasson S, Thompson A, Feist G, Ghribi O. Regulation of beta-amyloid levels in the brain of cholesterol-fed rabbit, a model system for sporadic Alzheimer’s disease. Mech Ageing Dev. 2008;129(11):649-655.
• [30] Prasanthi JR, Dasari B, Marwarha G, Larson T, Chen X, Geiger JD. Caffeine protects against oxidative stress and Alzheimer’s disease-like pathology in rabbit hippocampus induced by cholesterol-enriched diet. Free Radic Biol Med. 2010;49(7):1212-1220.
• [31] Deci S, Lemieux SK, Smith-Bell CA, Sparks DL, Schreurs BG. Cholesterol increases ventricular volume in a rabbit model of Alzheimer’s disease. J Alzheimers Dis. 2012;29(2):283-292.
• [32] Ricciarelli R, Zingg JM, Azzi A. Vitamin E: Protective role of a Janus molecule. FASEB J. 2001;15(13):2314-2325.
• [33] Aytan N, Jung T, Tamturk F, Grune T, Kartal-Ozer N. Oxidative stress related changes in the brain of hypercholesterolemic rabbits. Biofactors. 2008;33(3):225-236.
• [34] Hoozemans JJ, Veerhuis R, Van Haastert ES, Rozemuller JM, Baas F, Eikelenboom P. The unfolded protein response is activated in Alzheimer’s disease. Acta Neuropathol. 2005;110(2):165-172.
• [35] Lu J, Wu DM, Hu B, Cheng W, Zheng YL, Zhang ZF. Chronic administration of troxerutin protects mouse brain against D-galactose-induced impairment of cholinergic system. Neurobiol Learn Mem. 2010;93(2):157-164.
• [36]Cai M, Wang H, Li JJ, Zhang YL, Xin L, Li F. The signaling mechanisms of hippocampal endoplasmic reticulum stress affecting neuronal plasticity-related protein levels in high fat diet-induced obese rats and the regulation of aerobic exercise. Brain Behav Immun. 2016;57:347-359
• [37] Wang H, Wang X, Ke ZJ, Comer AL, Xu M, Frank JA. Tunicamycininduced unfolded protein response in the developing mouse brain. Toxicol Appl Pharmacol. 2015;283(3):157-167.
• [38] Onoda A, Kawasaki T, Tsukiyama K, Takeda K, Umezawa M. Carbon nanoparticles induce endoplasmic reticulum stress around blood vessels with accumulation of misfolded proteins in the developing brain of offspring. Sci Rep. 2020;10(1):10028.
• [39] Ciechanover A, Kwon YT. Degradation of misfolded proteins in neurodegenerative diseases: therapeutic targets and strategies. Exp Mol Med. 2015;47:e147.
• [40] Remondelli P, Renna M. The endoplasmic reticulum unfolded protein response in neurodegenerative disorders and its potential therapeutic significance. Front Mol Neurosci. 2017;10:187.
• [41] Chi H, Chang HY, Sang TK. Neuronal cell death mechanisms in major neurodegenerative diseases. Int J Mol Sci. 2018;19(10):3082.
• [42] El-Sayyad HI, El-Sherbiny MA, Sobh MA, Abou-El-Naga AM, Ibrahim MA, Mousa SA. Protective effects of Morus alba leaves extract on ocular functions of pups from diabetic and hypercholesterolemic mother rats. Int J Biol Sci. 2011;7(6):715- 728.
• [43] Tan JL, Li QX, Ciccotosto GD, Crouch PJ, Culvenor JG, White AR. Mild oxidative stress induces redistribution of BACE1 in non-apoptotic conditions and promotes the amyloidogenic processing of Alzheimer’s disease amyloid precursor protein. PLoS One. 2013;8(4):e61246.
• [44] Hill KE, Montine TJ, Motley AK, Li X, May JM, Burk RF. Combined deficiency of vitamins E and C causes paralysis and death in guinea pigs. Am J Clin Nutr. 2003;77(6):1484-1488.
• [45] Pahrudin Arrozi A, Shukri SNS, Wan Ngah WZ, Mohd Yusof YA, Ahmad Damanhuri MH, Jaafar F. Comparative effects of alpha – and gamma-tocopherol on mitochondrial functions in Alzheimer’s Disease in vitro model. Sci Rep. 2020;10(1):8962