Glucose oxidation and low-density lipoprotein-induced macrophage ceroid accumulation: possible implications for diabetic atherosclerosis - PubMed (original) (raw)

Glucose oxidation and low-density lipoprotein-induced macrophage ceroid accumulation: possible implications for diabetic atherosclerosis

J V Hunt et al. Biochem J. 1994.

Abstract

The exposure of proteins to high concentrations of glucose in vitro is widely considered a relevant model of the functional degeneration of tissue occurring in diabetes mellitus. In particular, the enhanced atherosclerosis in diabetes is often discussed in terms of glycation of low-density lipoprotein (LDL), the non-enzymic attachment of glucose to apolipoprotein amino groups. However, glucose can undergo transition-metal-catalysed oxidation under near-physiological conditions in vitro, producing oxidants that possess a reactivity similar to the hydroxyl radical. These oxidants can fragment protein, hydroxylate benzoic acid and induce lipid peroxidation in human LDL. In this study, glycation of LDL in vitro is accompanied by such oxidative processes. However, the oxidation of LDL varies with glucose concentration in a manner which does not parallel changes in protein glycation. Glycation increases in proportion to glucose concentration, whereas in our studies maximal oxidation occurs at a glucose concentration of approx. 25 mM. The modification of LDL resulting from exposure to glucose alters macrophage ceroid accumulation, a process which occurs in the human atherosclerotic plaque. The accumulation of ceroid in macrophages is shown to be related to LDL oxidation rather than LDL glycation, per se, as it too occurs at a maximum of approx. 25 mM. Oxidative sequelae of protein glycation appear to be a major factor in LDL-macrophage interactions, at least with respect to ceroid accumulation. Our observations are discussed in the context of the observed increase in the severity of atherosclerosis in diabetes.

PubMed Disclaimer

Cited by

Proatherogenic Sialidases and Desialylated Lipoproteins: 35 Years of Research and Current State from Bench to Bedside.
Mezentsev A, Bezsonov E, Kashirskikh D, Baig MS, Eid AH, Orekhov A. Mezentsev A, et al. Biomedicines. 2021 May 25;9(6):600. doi: 10.3390/biomedicines9060600. Biomedicines. 2021. PMID: 34070542 Free PMC article. Review.
In vitro antioxidant and antidiabetic activity of essential oils encapsulated in gelatin-pectin particles against sugar, lipid and protein oxidation and amylase and glucosidase activity.
Siahbalaei R, Kavoosi G, Shakeri R. Siahbalaei R, et al. Food Sci Nutr. 2020 Oct 7;8(12):6457-6466. doi: 10.1002/fsn3.1935. eCollection 2020 Dec. Food Sci Nutr. 2020. PMID: 33312531 Free PMC article.
Protective action on human LDL against oxidation and glycation by four organosulfur compounds derived from garlic.
Ou CC, Tsao SM, Lin MC, Yin MC. Ou CC, et al. Lipids. 2003 Mar;38(3):219-24. doi: 10.1007/s11745-003-1054-4. Lipids. 2003. PMID: 12784861
The pathomorphological alterations of endocardial endothelium in experimental diabetes and diabetes associated with hyperlipidemia.
Popov D, Sima A, Stern D, Simionescu M. Popov D, et al. Acta Diabetol. 1996 Mar;33(1):41-7. doi: 10.1007/BF00571939. Acta Diabetol. 1996. PMID: 8777284
Increased atherosclerosis in streptozotocin-induced diabetic mice.
Kunjathoor VV, Wilson DL, LeBoeuf RC. Kunjathoor VV, et al. J Clin Invest. 1996 Apr 1;97(7):1767-73. doi: 10.1172/JCI118604. J Clin Invest. 1996. PMID: 8601643 Free PMC article.

References

1. Metabolism. 1981 Jun;30(6):572-7 - PubMed
1. Diabetes. 1980 Nov;29(11):882-8 - PubMed
1. Diabetes. 1982 Apr;31(4 Pt 1):283-91 - PubMed
1. Atherosclerosis. 1982 Oct;45(1):11-5 - PubMed
1. Eur J Biochem. 1983 Apr 5;131(3):535-8 - PubMed

Glucose oxidation and low-density lipoprotein-induced macrophage ceroid accumulation: possible implications for diabetic atherosclerosis - PubMed (original) (raw)