Sterculic Acid Antagonizes 7-ketocholesterol-mediated Inflammation and Inhibits Choroidal Neovascularization

Overview

Journal Biochim Biophys Acta

Specialties Biochemistry
Biophysics

Date 2012 Feb 21

PMID 22342272

Citations 18

Authors

Jiahn-Dar Huang

Juan Amaral

Jung Wha Lee

Ignacio M Larrayoz

Ignacio R Rodriguez

Affiliations

Soon will be listed here.

Abstract

Sterculic acid is a cyclopropene fatty acid with numerous biological activities. In this study we demonstrate that sterculic acid is a potent inhibitor of endoplasmic reticulum (ER) stress and related inflammation caused by 7-ketocholesterol (7KCh). 7KCh is a highly toxic oxysterol suspected in the pathogenesis of various age-related diseases such as atherosclerosis, Alzheimer's disease and age-related macular degeneration. Sterculic acid demonstrated to be 5-10 times more effective than other anti-inflammatory fatty acids at inhibiting 7KCh-mediated inflammatory responses in cultured cells. In vivo, sterculic acid was effective at inhibiting the formation of choroidal neovascularization (CNV) in the laser-injury rat model. Our data suggests that sterculic acid may be useful in treating CNV in certain forms of age-related macular degeneration.

Citing Articles

Phytol from prevents NF-κB-mediated inflammatory responses during macrophage polarization.

Duraisamy P, Angusamy A, Ravi S, Krishnan M, Martin L, Manikandan B 3 Biotech. 2024; 14(3):80.

PMID: 38375513 PMC: 10874368. DOI: 10.1007/s13205-024-03924-9.

Role of traditional Chinese medicine in age-related macular degeneration: exploring the gut microbiota's influence.

Yu Y, Liu Y, Meng Z Front Pharmacol. 2024; 15:1356324.

PMID: 38333011 PMC: 10850396. DOI: 10.3389/fphar.2024.1356324.

Oxysterols as Biomarkers of Aging and Disease.

Dias I, Shokr H Adv Exp Med Biol. 2023; 1440:307-336.

PMID: 38036887 DOI: 10.1007/978-3-031-43883-7_16.

Targeting 7KCh-Induced Cell Death Response Mediated by p38, P2X7 and GSDME in Retinal Pigment Epithelium Cells with Sterculic Acid.

Pariente A, Pelaez R, Ochoa R, Perez-Sala A, Villanueva-Martinez A, Bobadilla M Pharmaceutics. 2023; 15(11).

PMID: 38004569 PMC: 10675123. DOI: 10.3390/pharmaceutics15112590.

Identification of 7-Ketocholesterol-Modulated Pathways and Sterculic Acid Protective Effect in Retinal Pigmented Epithelium Cells by Using Genome-Wide Transcriptomic Analysis.

Pariente A, Perez-Sala A, Ochoa R, Bobadilla M, Villanueva-Martinez A, Pelaez R Int J Mol Sci. 2023; 24(8).

PMID: 37108627 PMC: 10144535. DOI: 10.3390/ijms24087459.

References

Nelson T, Alkon D . Oxidation of cholesterol by amyloid precursor protein and beta-amyloid peptide. J Biol Chem. 2004; 280(8):7377-87. DOI: 10.1074/jbc.M409071200. View

Poli G, Sottero B, Gargiulo S, Leonarduzzi G . Cholesterol oxidation products in the vascular remodeling due to atherosclerosis. Mol Aspects Med. 2009; 30(3):180-9. DOI: 10.1016/j.mam.2009.02.003. View

Busch T, King A . Stability of Cholesterol, 7-Ketocholesterol and β-Sitosterol during Saponification: Ramifications for Artifact Monitoring of Sterol Oxide Products. J Am Oil Chem Soc. 2010; 87(9):955-962. PMC: 2923713. DOI: 10.1007/s11746-010-1572-3. View

Tabas I, Ron D . Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat Cell Biol. 2011; 13(3):184-90. PMC: 3107571. DOI: 10.1038/ncb0311-184. View

Sasaki H, Watanabe F, Murano T, Miyashita Y, Shirai K . Vascular smooth muscle cell apoptosis induced by 7-ketocholesterol was mediated via Ca2+ and inhibited by the calcium channel blocker nifedipine. Metabolism. 2007; 56(3):357-62. DOI: 10.1016/j.metabol.2006.10.017. View

Salminen A, Kauppinen A, Hyttinen J, Toropainen E, Kaarniranta K . Endoplasmic reticulum stress in age-related macular degeneration: trigger for neovascularization. Mol Med. 2010; 16(11-12):535-42. PMC: 2972399. DOI: 10.2119/molmed.2010.00070. View

Lordan S, Mackrill J, OBrien N . Oxysterols and mechanisms of apoptotic signaling: implications in the pathology of degenerative diseases. J Nutr Biochem. 2009; 20(5):321-36. DOI: 10.1016/j.jnutbio.2009.01.001. View

Rodriguez I, Larrayoz I . Cholesterol oxidation in the retina: implications of 7KCh formation in chronic inflammation and age-related macular degeneration. J Lipid Res. 2010; 51(10):2847-62. PMC: 2936760. DOI: 10.1194/jlr.R004820. View

Bao X, Katz S, Pollard M, Ohlrogge J . Carbocyclic fatty acids in plants: biochemical and molecular genetic characterization of cyclopropane fatty acid synthesis of Sterculiafoetida. Proc Natl Acad Sci U S A. 2002; 99(10):7172-7. PMC: 124547. DOI: 10.1073/pnas.092152999. View

10.

Psota T, Gebauer S, Kris-Etherton P . Dietary omega-3 fatty acid intake and cardiovascular risk. Am J Cardiol. 2006; 98(4A):3i-18i. DOI: 10.1016/j.amjcard.2005.12.022. View

11.

Carpenter K, Guardiola F, Stein B, Mitchinson M . Oxysterol profiles of normal human arteries, fatty streaks and advanced lesions. Free Radic Res. 2001; 35(1):31-41. DOI: 10.1080/10715760100300571. View

12.

Ong W, Goh E, Lu X, Farooqui A, Patel S, Halliwell B . Increase in cholesterol and cholesterol oxidation products, and role of cholesterol oxidation products in kainate-induced neuronal injury. Brain Pathol. 2003; 13(3):250-62. PMC: 8095968. DOI: 10.1111/j.1750-3639.2003.tb00026.x. View

13.

Stahl A, Connor K, Sapieha P, Chen J, Dennison R, Krah N . The mouse retina as an angiogenesis model. Invest Ophthalmol Vis Sci. 2010; 51(6):2813-26. PMC: 2891451. DOI: 10.1167/iovs.10-5176. View

14.

Sottero B, Gamba P, Gargiulo S, Leonarduzzi G, Poli G . Cholesterol oxidation products and disease: an emerging topic of interest in medicinal chemistry. Curr Med Chem. 2009; 16(6):685-705. DOI: 10.2174/092986709787458353. View

15.

BLIGH E, Dyer W . A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959; 37(8):911-7. DOI: 10.1139/o59-099. View

16.

Wajant H, Pfizenmaier K, Scheurich P . Tumor necrosis factor signaling. Cell Death Differ. 2003; 10(1):45-65. DOI: 10.1038/sj.cdd.4401189. View

17.

Vejux A, Lizard G . Cytotoxic effects of oxysterols associated with human diseases: Induction of cell death (apoptosis and/or oncosis), oxidative and inflammatory activities, and phospholipidosis. Mol Aspects Med. 2009; 30(3):153-70. DOI: 10.1016/j.mam.2009.02.006. View

18.

Saito E, Wachi H, Sato F, Seyama Y . 7-ketocholesterol, a major oxysterol, promotes pi-induced vascular calcification in cultured smooth muscle cells. J Atheroscler Thromb. 2008; 15(3):130-7. DOI: 10.5551/jat.e556. View

19.

Rodriguez I, Alam S, Lee J . Cytotoxicity of oxidized low-density lipoprotein in cultured RPE cells is dependent on the formation of 7-ketocholesterol. Invest Ophthalmol Vis Sci. 2004; 45(8):2830-7. DOI: 10.1167/iovs.04-0075. View

20.

Brown A, Leong S, Dean R, Jessup W . 7-Hydroperoxycholesterol and its products in oxidized low density lipoprotein and human atherosclerotic plaque. J Lipid Res. 1997; 38(9):1730-45. View