A proper regulation of membrane fluidity is critical for cellular activities such as communication between cells, mitosis, and endocytosis. Unsaturated lipids, a main component of biological membranes, are particularly susceptible to oxidative attack of reactive oxygen species. The oxidation of lipids can produce structural derangement of membranes and eventually alter the membrane fluidity. We have applied fluorescence correlation spectroscopy (FCS) and Raman spectroscopy to investigate the fluidity and structure of model membranes subject to oxidative attack. Hydrogen peroxide has little effect on the lateral fluidity of membranes, whereas hydroxyl radical causes a significantly increased fluidity. The latter is rationalized with the cleavage of the acyl chains of lipids caused by hydroxyl radical; this interpretation is founded on the diminished intensities of lines in Raman spectra associated with -CH(2) and C═C moieties in lipids and supported by mass-spectral measurements. The same approach provides a mechanistic account of the inhibitory capability of vitamins C and E against the increased membrane fluidity resulting from an oxidative attack. Membranes with much cholesterol exhibit a novel resistance against altered membrane fluidity induced with oxidative attack; this finding has biological implications. Our approach combining FCS and Raman measurements reveals the interplay between the structure and fluidity of membranes and provides insight into the pathophysiology of cellular oxidative injury.
and lipid oxidation. In the present study, we aimed to investigate the effects of probucol on high fat-high cholesterol (HFHC) diet-induced hyperlipidemia and atherosclerotic lesions, and the effects of oxidative stress in mice. Thirty male C57BL/6 J mice and thirty male apo E knockout (apoE -/-) mice were randomly divided into three groups (control group, HFHC group and HFHC-probucol group; n ¼ 10, each group). The animals in control group were fed normal diet. HFHC mice were fed a high fat/high cholesterol diet (15% lard and 0.25% cholesterol). HFHC-probucol group was supplemented with 0.5% probucol in HFHC diet. We examined the correlative index at the end of 12 weeks. The levels of serum lipid were increased in HFHC groups compared with the control group (P < 0.05), and were significantly lowered in probucol treatment group compared with respective HFHC group (P < 0.05). Serious lesions of the aorta in C57BL/6 J mice were not observed. HFHC and probucol treatment resulted in a significant reduction of aorta lesion area in apoE -/mice compared with HFHC group. Probucol contributed to a significant decrease of lipid content of the liver tissue in both C57BL/6 J and apoE -/mice as showed by hematoxylin-eosin staining. Furthermore, compared with respective control groups, the serum (MDA) contents, oxidized low density lipioprotein (ox-LDL) contents, C-reactive protein (CRP) activity, and glutathione S-transferase (GST) activity were increased, and the levels of total antioxidative capacity (T-AOC), total superoxide dismutase (T-SOD) activity, and paraoxonase 1 (PON1) activity were decreased in HFHC-treatment mice (P < 0.05), and these changes were attenuated or reversed by probucol treatment (P < 0.05). Probucol improved PON1 activities and upregulated PON1, CRP mRNA expression in liver (P < 0.05). These results show that probucol contributed significantly to prevent the oxidative stress, upregulate the PON1 expressions in the livers and increase the serum PON1 activity in the high fat-high cholesterol diet-induced hyperlipidemic mice, suggesting the potential therapeutic effects of probucol in atherosclerosis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.