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- Mattsson Hultén, Lillemor, 1951, et al.
(författare)
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Human macrophages limit oxidation products in low density lipoprotein
- 2005
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Ingår i: Lipids Health Dis. - : BioMed Central (BMC). - 1476-511X. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- This study tested the hypothesis that human macrophages have the ability to modify oxidation products in LDL and oxidized LDL (oxLDL) via a cellular antioxidant defence system. While many studies have focused on macrophage LDL oxidation in atherosclerosis development, less attention has been given to the cellular antioxidant capacity of these cells. Compared to cell-free controls (6.2 +/- 0.7 nmol/mg LDL), macrophages reduced TBARS to 4.42 +/- 0.4 nmol/mg LDL after 24 h incubation with LDL (P = 0.022). After 2 h incubation with oxLDL, TBARS were 3.69 +/- 0.5 nmol/mg LDL in cell-free media, and 2.48 +/- 0.9 nmol/mg LDL in the presence of macrophages (P = 0.034). A reduction of lipid peroxides in LDL (33.7 +/- 6.6 nmol/mg LDL) was found in the presence of cells after 24 h compared to cell-free incubation (105.0 +/- 14.1 nmol/mg LDL) (P = 0.005). The levels of lipid peroxides in oxLDL were 137.9 +/- 59.9 nmol/mg LDL and in cell-free media 242 +/- 60.0 nmol/mg LDL (P = 0.012). Similar results were obtained for hydrogen peroxide. Reactive oxygen species were detected in LDL, acetylated LDL, and oxLDL by isoluminol-enhanced chemiluminescence (CL). Interestingly, oxLDL alone gives a high CL signal. Macrophages reduced the CL response in oxLDL by 45% (P = 0.0016). The increased levels of glutathione in oxLDL-treated macrophages were accompanied by enhanced catalase and glutathione peroxidase activities. Our results suggest that macrophages respond to oxidative stress by endogenous antioxidant activity, which is sufficient to decrease reactive oxygen species both in LDL and oxLDL. This may suggest that the antioxidant activity is insufficient during atherosclerosis development. Thus, macrophages may play a dual role in atherogenesis, i.e. both by promoting and limiting LDL-oxidation.
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| 2. |
- van Reyk, D. M., et al.
(författare)
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Oxysterols in biological systems: sources, metabolism and pathophysiological relevance
- 2006
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Ingår i: Redox Rep. - 1743-2928. ; 11:6, s. 255-62
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Tidskriftsartikel (refereegranskat)abstract
- Oxysterols are the 27-carbon products of cholesterol oxidation by both enzymic and non-enzymic mechanisms. Their roles in cholesterol homeostasis, as well as in diseases in which oxidative damage and lipid peroxidation are implicated (e.g. atherosclerosis), have been investigated extensively. However, there are a number of important considerations regarding the physiological/pathophysiological functions and activities of the different oxysterols. First, in both normal and diseased tissues, the levels of oxysterols are very low when compared to the native sterol. Also, when assessing studies that have measured the levels of oxysterols in biological samples, there must be careful consideration as to the method of sample isolation, storage and sampling. This is because of the potential generation or loss of oxysterols during these procedures. Additionally, the relevance of in vitro studies which examine the effects of oxysterols upon cell function should be judged as to cellular oxysterol content (both in terms of the levels of oxysterol and the degree of esterification) resulting from the oxysterol treatment. We present evidence that the means by which oxysterol is delivered in vitro determines whether the oxysterol content reflects what has been found in vivo. Studies identifying the specific cellular targets of oxysterol indicate that several oxysterols may be regulators of cellular lipid metabolism via control of gene transcription.
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