Journal of Isfahan Medical School

Journal of Isfahan Medical School

The Effect of 24-Hydroxy Cholesterol on Production of Reactive Oxygen Species (ROS) in Cultured Astrocytes Treated by Beta Amyloid

Document Type : Original Article (s)

Authors
Zahra Nazeri 1
Shirin Azizidoost 2
Maryam Cheraghzadeh 3
Bahar Sepiani 1
Alireza Kheirollah 4
1 MSc Student, Department of Biochemistry, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
2 PhD Student, Department of Biochemistry, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
3 PhD in Molecular Genetics, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
4 Associate Professor, Department of Biochemistry, School of Medicine, Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
10.22122/jims.v36i482.9989
Abstract
Background: Alzheimer's disease is a neurodegenerative disorder characterized by the accumulation of beta-amyloid plaques outside the cells, and intracellular hyperphosphorylation of tau protein. Amyloid beta is involved in both the pathogenesis of Alzheimer's disease and induction of reactive oxygen species (ROS). Since 24-hydroxy cholesterol (24-OHCho) as a polar metabolite can eliminate excess cholesterol in the brain, we investigated the regulatory role of 24-hydroxy cholesterol on the level of reactive oxygen species induced by exogenous cholesterol and amyloid beta.Methods: Astrocytes were isolated from the brain of newborn C57BL/6 mice, and cultured in Dulbecco's modified Eagle's medium (DMEM) + 10% fetal bovine serum (FBS). Intracellular reactive oxygen species were measured in cells treated with various concentration of cholesterol by fluorimeter, and also in the presence of beta amyloid with or without of 24-hydroxy cholesterol. Results were analyzed using ANOVA test via SPSS software.Findings: The production of reactive oxygen species was significantly increased when astrocytes were treated with exogenous cholesterol or amyloid beta, compare to control. However, treating with 24-hydroxy cholesterol significantly decreased the level of reactive oxygen species in beta-amyloid group.Conclusion: Based on various reports, beta-amyloid increases cholesterol levels in patients with Alzheimer’s disease. On the other hand, 24-hydroxy cholesterol is one of the important factors in regulating cholesterol homeostasis in the brain, and plays an efficient role in reduction of intracellular generation of reactive oxygen species in the case of Alzheimer’s disease, by reduction of cholesterol.
Keywords
Alzheimer
Amyloid beta
24-hydroxy cholesterol
Cholesterol
Reactive oxygen species
  1. Kodamullil AT, Younesi E, Naz M, Bagewadi S, Hofmann-Apitius M. Computable cause-and-effect models of healthy and Alzheimer's disease states and their mechanistic differential analysis. Alzheimers Dement 2015; 11(11): 1329-39.
  2. Eufemi M, Cocchiola R, Romaniello D, Correani V, Di FL, Fabrizi C, et al. Acetylation and phosphorylation of STAT3 are involved in the responsiveness of microglia to beta amyloid. Neurochem Int 2015; 81: 48-56.
  3. Lombardo S, Maskos U. Role of the nicotinic acetylcholine receptor in Alzheimer's disease pathology and treatment. Neuropharmacology 2015; 96(Pt B): 255-62.
  4. Singh M, Kaur M, Kukreja H, Chugh R, Silakari O, Singh D. Acetylcholinesterase inhibitors as Alzheimer therapy: from nerve toxins to neuroprotection. Eur J Med Chem 2013; 70: 165-88.
  5. Miranda S, Opazo C, Larrondo LF, Munoz FJ, Ruiz F, Leighton F, et al. The role of oxidative stress in the toxicity induced by amyloid beta-peptide in Alzheimer's disease. Prog Neurobiol 2000; 62(6): 633-48.
  6. Spuch C, Ortolano S, Navarro C. New insights in the amyloid-Beta interaction with mitochondria. J Aging Res 2012; 2012: 324968.
  7. Murphy RC, Johnson KM. Cholesterol, reactive oxygen species, and the formation of biologically active mediators. J Biol Chem 2008; 283(23): 15521-5.
  8. Maciel EN, Vercesi AE, Castilho RF. Oxidative stress in Ca(2+)-induced membrane permeability transition in brain mitochondria. J Neurochem 2001; 79(6): 1237-45.
  9. Lecis C, Segatto M. Cholesterol Homeostasis Imbalance and Brain Functioning : Neurological Disorders and Behavioral. Journal of Neurology and Neurological Disorders 2015; 1(1): 1-14.
  10. L__tjohann D, Meichsner S, Pettersson H. Lipids in Alzheimer_آs disease and their potential for therapy. Clinical Lipidology 2012; 7(1): 65-78.
  11. Leoni V, Caccia C. 24S-hydroxycholesterol in plasma: a marker of cholesterol turnover in neurodegenerative diseases. Biochimie 2013; 95(3): 595-612.
  12. Abildayeva K, Jansen PJ, Hirsch-Reinshagen V, Bloks VW, Bakker AH, Ramaekers FC, et al. 24(S)-hydroxycholesterol participates in a liver X receptor-controlled pathway in astrocytes that regulates apolipoprotein E-mediated cholesterol efflux. J Biol Chem 2006; 281(18): 12799-808.
  13. Gibson WW, Eckert GP, Igbavboa U, Muller WE. Amyloid beta-protein interactions with membranes and cholesterol: causes or casualties of Alzheimer's disease. Biochim Biophys Acta 2003; 1610(2): 281-90.
  14. Gamba P, Leonarduzzi G, Tamagno E, Guglielmotto M, Testa G, Sottero B, et al. Interaction between 24-hydroxycholesterol, oxidative stress, and amyloid-beta in amplifying neuronal damage in Alzheimer's disease: three partners in crime. Aging Cell 2011; 10(3): 403-17.
  15. Ito J, Nagayasu Y, Lu R, Kheirollah A, Hayashi M, Yokoyama S. Astrocytes produce and secrete FGF-1, which promotes the production of apoE-HDL in a manner of autocrine action. J Lipid Res 2005; 46(4): 679-86.
  16. Ferrera P, Mercado-Gomez O, Silva-Aguilar M, Valverde M, Arias C. Cholesterol potentiates beta-amyloid-induced toxicity in human neuroblastoma cells: involvement of oxidative stress. Neurochem Res 2008; 33(8): 1509-17.
  17. Dasari B, Prasanthi JR, Marwarha G, Singh BB, Ghribi O. Cholesterol-enriched diet causes age-related macular degeneration-like pathology in rabbit retina. BMC Ophthalmol 2011; 11: 22.
  18. Refolo LM, Malester B, LaFrancois J, Bryant-Thomas T, Wang R, Tint GS, et al. Hypercholesterolemia accelerates the Alzheimer's amyloid pathology in a transgenic mouse model. Neurobiol Dis 2000; 7(4): 321-31.
  19. Bogdanovic N, Bretillon L, Lund EG, Diczfalusy U, Lannfelt L, Winblad B, et al. On the turnover of brain cholesterol in patients with Alzheimer's disease. Abnormal induction of the cholesterol-catabolic enzyme CYP46 in glial cells. Neurosci Lett 2001; 314(1-2): 45-8.
  20. Angelova PR, Abramov AY. Interaction of neurons and astrocytes underlies the mechanism of Abeta-induced neurotoxicity. Biochem Soc Trans 2014; 42(5): 1286-90.
  21. Noguchi N, Saito Y, Urano Y. Diverse functions of 24(S)-hydroxycholesterol in the brain. Biochem Biophys Res Commun 2014; 446(3): 692-6.
  22. Sato Y, Bernier F, Yamanaka Y, Aoshima K, Oda Y, Ingelsson M, et al. Reduced plasma desmosterol-to-cholesterol ratio and longitudinal cognitive decline in Alzheimer's disease. Alzheimers Dement (Amst ) 2015; 1(1): 67-74.
  23. Prasanthi JR, Huls A, Thomasson S, Thompson A, Schommer E, Ghribi O. Differential effects of 24-hydroxycholesterol and 27-hydroxycholesterol on beta-amyloid precursor protein levels and processing in human neuroblastoma SH-SY5Y cells. Mol Neurodegener 2009; 4: 1.
  24. Wang Y, Rogers PM, Su C, Varga G, Stayrook KR, Burris TP. Regulation of cholesterologenesis by the oxysterol receptor, LXRalpha. J Biol Chem 2008; 283(39): 26332-9.
  25. Wong J, Quinn CM, Brown AJ. SREBP-2 positively regulates transcription of the cholesterol efflux gene, ABCA1, by generating oxysterol ligands for LXR. Biochem J 2006; 400(3): 485-91.
Journal of Isfahan Medical School
Volume 36, Issue 482 - Serial Number 482
May and June 2018
Pages 607-613

  • Receive Date 22 April 2018
  • Accept Date 06 April 2022