scholarly journals Autophagy Induction Protects against 7-Oxysterol-induced Cell Death via Lysosomal Pathway and Oxidative Stress

2016 ◽  
Vol 9 ◽  
pp. JCD.S37841 ◽  
Author(s):  
Xi-Ming Yuan ◽  
Nargis Sultana ◽  
Nabeel Siraj ◽  
Liam J. Ward ◽  
Bijar Ghafouri ◽  
...  

7-Oxysterols are major toxic components in oxidized low-density lipoprotein and human atheroma lesions, which cause lysosomal membrane permeabilization (LMP) and cell death. Autophagy may function as a survival mechanism in this process. Here, we investigated whether 7-oxysterols mixed in an atheroma-relevant proportion induce autophagy, whether autophagy induction influences 7-oxysterol-mediated cell death, and the underlying mechanisms, by focusing on cellular lipid levels, oxidative stress, and LMP in 7-oxysterol-treated macrophages. We found that 7-oxysterols induced cellular lipid accumulation, autophagy dysfunction, and cell death in the form of both apoptosis and necrosis. Exposure to 7-oxysterols induced autophagic vacuole synthesis in the form of increased autophagy marker microtubule-associated protein 1A/1B-light chain 3 (LC3) and LC3-phosphatidylethanolamine conjugate (LC3-II) and autophagic vacuole formation. This led to an accumulation of p62, indicating a reduction in autophagic vacuole degradation. Importantly, autophagy induction significantly reduced 7-oxysterol-mediated cell death by diminishing LMP and oxidative stress. Moreover, autophagy induction minimized cellular lipid accumulation induced by 7-oxysterols. These findings highlight the importance of autophagy in combating cellular stress, LMP, and cell death in atherosclerosis. Therefore, activation of the autophagy pathway may be a potential therapeutic strategy for prevention of necrotic core formation in atherosclerotic lesions.

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Zoe Irwin ◽  
Emeir M. McSorley ◽  
Mary M. Slevin ◽  
Lisa Rowan ◽  
Paul McMillen ◽  
...  

AbstractEvidence from observational studies indicates that seaweed consumption may reduce the risk of non-communicable diseases such as cardiovascular disease, type two diabetes, and obesity. Accumulating evidence from in vitro and animal studies suggest seaweed have antihyperlipidemic, anti-inflammatory and antioxidant properties which may in part be attributed to the high content of soluble dietary fibre in seaweeds. The viscosity of seaweed fibres is suggested to mediate antihyperlipdiemic effects via the alteration of lipid/bile acid absorption kinetics to decrease low-density lipoprotein cholesterol (LDL). Thus, there is a need to evaluate the efficacy of seaweed derived dietary fibre in the management of dyslipidemia. Therefore, the aim of this study was to determine the effect of a fibre rich extract from Palmaria palmata on the lipid profile as well as markers of inflammation and oxidative stress in healthy adults. A total of 60 healthy participants (30 male and 30 female) aged 20 to 58 years, were assigned to consume the Palmaria palmata fibre extract (5g/day), Synergy-1 and the placebo (maltodextrin) for a duration of 4 weeks with a minimum 4 week washout between each treatment in a double blind, randomised crossover study conducted over 5 months. Fasting concentrations of cholesterol, triglycerides and high-density lipoprotein cholesterol (HDL) were analysed and low-density lipoprotein cholesterol (LDL) and LDL: HDL ratio was calculated. C-reactive protein (CRP) and Ferric Reducing Ability of Plasma (FRAP) were analysed as markers of inflammation and oxidative stress, respectively. Supplementation for 4 weeks with Palmaria palmata resulted in favourable changes to lipid profiles with a reduced LDL:HDL ratio; however intention-to-treat univariate ANCOVA identified no significant difference between the treatment groups over time on any of the lipid profile markers. A non-significant increase in CRP and triglyceride concentration along with lower FRAP was also observed with Palmaria palmata supplementation. Evidence from this study suggests that Palmaria palmata may have effects on lipid metabolism and appears to mobilise triglycerides. More research is needed in individuals with dyslipidaemia to fully elucidate these effects.


1984 ◽  
Vol 99 (4) ◽  
pp. 1266-1274 ◽  
Author(s):  
D J Falcone ◽  
N Mated ◽  
H Shio ◽  
C R Minick ◽  
S D Fowler

The sequestration of low-density lipoprotein (LDL) by components of the vascular extracellular matrix has long been recognized as a contributing factor to lipid accumulation during atherogenesis. The effects, however, that components of the extracellular matrix might have on LDL catabolism by scavenger cells have been little investigated. For these purposes we have prepared insoluble complexes of LDL, heparin, fibronectin, and denatured collagen (gelatin) and examined their effects on lipid accumulation, LDL uptake and degradation, and cholesteryl ester synthesis in mouse peritoneal macrophages. The results of these experiments have demonstrated that the cholesteryl ester content of macrophages incubated with a particular suspension of LDL, heparin, fibronectin, and collagen complexes is four- to fivefold that of cells incubated with LDL alone. The uptake of complexes containing 125I-LDL is rapid; however, in contrast to either endocytosed 125I-LDL or 125I-acetyl LDL, the degradation of complex-derived LDL is impaired. In addition, the uptake of complex-derived LDL stimulates the incorporation of [14C]oleic acid into cholesteryl oleate, however, the stimulation was a small fraction of that observed in cells incubated with acetyl LDL. Ultrastructurally, macrophages incubated with LDL, heparin, fibronectin, and collagen complexes did not contain many lipid droplets, but rather their cytoplasm is filled with phagosomes containing material similar in appearance to LDL-matrix complexes. These results indicate that components of the extracellular matrix can alter the catabolism of LDL by scavenger cells, suggesting that they may play a role in cellular lipid accumulation in the atherosclerotic lesion.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Hui-Yu Huang ◽  
Mallikarjuna Korivi ◽  
Ying-Ying Chaing ◽  
Ting-Yi Chien ◽  
Ying-Chieh Tsai

Pleurotus tuber-regiumcontains polysaccharides that are responsible for pharmacological actions, and medicinal effects of these polysaccharides have not yet been studied in diabetic rats. We examined the antidiabetic, antihyperlipidemic, and antioxidant properties ofP. tuber-regiumpolysaccharides in experimental diabetic rats. Forty rats were equally assigned as diabetic high-fat (DHF) diet and polysaccharides treated DHF groups (DHF+1P, DHF+2P, and DHF+3P, 20 mg/kg bodyweight/8-week). Diabetes was induced by chronic low-dose streptozotocin injections and a high-fat diet to mimic type 2 diabetes. Polysaccharides (1P, 2P, and 3P) were extracted from three different strains ofP. tuber-regium. Fasting blood glucose and glycosylated hemoglobin (HbA1c) levels substantially decreased, while serum insulin levels were restored by polysaccharides treatment compared to DHF. Furthermore, plasma total cholesterol, triglycerides, and low-density lipoprotein levels were significantly(P<0.01)lower in polysaccharide groups. High-density lipoprotein levels were attenuated with polysaccharides against diabetes condition. Polysaccharides inhibited(P<0.01)the lipid peroxidation index (malondialdehyde), and restored superoxide dismutase and glutathione peroxidase activities in the liver of diabetic rats. The antihyperglycemic property of polysaccharides perhaps boosts the antioxidant system that attenuates oxidative stress. We emphasize thatP. tuber-regiumpolysaccharides can be considered as an alternative medicine to treat hyperglycemia and oxidative stress in diabetic rats.


2020 ◽  
pp. 1-3
Author(s):  
Deepthy C Sahadevan* ◽  
Archna Sing ◽  
Busi Karunanand ◽  
Himani Thakkar ◽  
Ajay Kumar Gautam

Objective: This study was designed to assess the apolipoprotein B (Apo-B), apolipoprotein A (Apo A) and Apo B/Apo A-I ratio in subjects with and withoutmetabolic syndrome andtoevaluate the correlationofApoB/ApoA-Iratiowithoxidative stressmarker andcardiovasculardisease risk. Methods:Atotal of 308 subjects including one hundred and fty- ve cases and one hundred and fty- three controls were recruited for this study. All the subjects were classied according to the NCEPATP III (National cholesterol education program – Adult treatment panel III) criteria for MetS. Anthropometric and clinical characteristics were recorded using clinical Proforma. Blood samples were collected for doing plasma glucose, Lipid prole analysis [Total Cholesterol (TC), Triglyceride (TG), high-density lipoprotein (HDL)], ApoA1, Apo B and oxidative stress marker - Malondialdehyde (MDA). Serum low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL) and Apo B/Apo A-I ratio were calculated. Comparison of data between the two groups was done by t test. Correlation coefcient of Apo B/ Apo A1 ratio with cadiometabolic risk factors were calculated. Result: We found that cardiometabolic risk factors like abdominal obesity, systolic and diastolic blood pressure, fasting plasma glucose, TG, atherogenic lipoproteins LDL, Apo B, Apo B/Apo A-I ratio and MDA were signicantly high in subjects with MetS whereas anti-atherogenic factor Apo A1 was signicantly low. We also observed that Apo B/AI ratio was positively related to cardiometabolic risk factors and with oxidative stress marker. Conclusion:Apo B/AI ratio was related to metabolic syndrome and was found to be a reliable indicator of cardiovascular risk in MetS.


2010 ◽  
Vol 80 (2) ◽  
pp. 97-106 ◽  
Author(s):  
Jae Soon Byun ◽  
Young Sun Han ◽  
Sang Sun Lee

Soy isoflavones have been reported to decrease the risk of atherosclerosis in postmenopausal women. However, the effects of dietary consumption of soybean have not been explored. In this study, we evaluated the effects of consuming yellow soybeans, black soybeans (Glycine max), or sword beans (Canavalia gladiate) on lipid and oxidative stress levels in an ovariectomized rat model. Forty-seven nine-week-old female rats were ovariectomized, randomly divided into four groups, and fed one of the following diets for 10 weeks: a diet supplemented with casein (NC, n = 12), a diet supplemented with yellow soybean (YS, n = 12), a diet supplemented with black soybean (BS, n = 12), or a diet supplemented with sword bean (SB, n = 11). Plasma triglyceride (TG) levels in the BS and SB groups were significantly lower than that in the NC group. Notably, the BS group had significantly lower plasma total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels than the other groups. Hepatic total lipid levels were significantly lower in the YS and SB groups, and cholesterol levels were significantly lower in the SB group than in the NC group. Superoxide dismutase (SOD) and catalase (CAT) activities were significantly higher in the groups fed beans compared to the NC group. Hepatic thiobarbituric acid reactive substances (TBARS) levels were also significantly lower in the BS and SB groups than the NC group. In conclusion, our results suggest that consumption of various types of beans may inhibit oxidative stress in postmenopausal women by increasing antioxidant activity and improving lipid profiles. Notably, intake of black soybean resulted in the greatest improvement in risk factors associated with cardiovascular disease.


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