The effect of ghrelin on antioxidant status in the rat's model of Alzheimer's disease induced by amyloid-beta.

Alzheimer's disease (AD) is a neurodegenerative disorder associated with amyloid-beta (Aß) plaque formation and oxidative stress in the brain. Ghrelin has been proven to exert antioxidant activity and neuroprotection in different neurological diseases. This study is going on to examine the effect of ghrelin on antioxidant status in the rat's model of AD induced by Aß. Cognitive impairment was induced by intra-hippocampal administration of Aß (10 µg) in Wistar rats and ghrelin (80 µg/kg) was administrated intraperitoneal for ten consecutive days. Behavior was assessed with Morris water maze and passive avoidance tests. Malondialdehyde (MDA) level as a marker of lipid peroxidation was assessed using the thiobarbituric acid. Catalase activity was assayed by the decomposition of H2O2. Antioxidant capacity was determined using the FRAP method. Treatment with ghrelin decreased the hippocampus and serum MDA levels in wild-type rodents and prevented an increase in hippocampal and serum MDA levels in animals receiving Aß. There was no significant change in the serum catalase activity between the studied groups. Hippocampus catalase activity was reduced in the Aß group and treatment with ghrelin increased it. The antioxidant capacity of the hippocampus and serum increased in the ghrelin-receiving control group. The hippocampus antioxidant capacity level decreased in the Aß group, and treatment with ghrelin increased it, but there were no significant changes in the serum antioxidant capacity of animals receiving Aß. These results provide evidence that the administration of ghrelin has antioxidant properties and protects against hippocampal lipid peroxidation in a rat model of AD.

Ameliorative effects of omega-lycotoxin-Gsp2671e purified from the spider venom of Lycosa praegrandis on memory deficits of glutamate-induced excitotoxicity rat model.

Memory impairment is one of the main complications of Alzheimer's disease (AD). This condition can be induced by hyper-stimulation of N-Methyl-D-aspartate receptors (NMDARs) of glutamate in the hippocampus, which ends up to pyramidal neurons determination. The release of neurotransmitters relies on voltage-gated calcium channels (VGCCs) such as P/Q-types. Omega-lycotoxin-Gsp2671e (OLG1e) is a P/Q-type VGCC modulator with high affinity and selectivity. This bio-active small protein was purified and identified from the Lycosa praegrandis venom. The effect of this state-dependent low molecular weight P/Q-type calcium modulator on rats was investigated via glutamate-induced excitotoxicity by N-Methyl-D-aspartate. Also, Electrophysiological amplitude of field excitatory postsynaptic potentials (fEPSPs) in the input-output and Long-term potentiation (LTP) curves were recorded in mossy fiber and the amount of synaptophysin (SYN), synaptosomal-associated protein, 25 kDa (SNAP-25), and synaptotagmin 1(SYT1) genes expression were measured using Real-time PCR technique for synaptic quantification. The outcomes of the current study suggest that OLG1e as a P/Q-type VGCC modulator has an ameliorative effect on excitotoxicity-induced memory defects and prevents the impairment of pyramidal neurons in the rat hippocampus.

Association Between Fat-soluble Vitamins and Lipid Profile in the Overweight Population.

BACKGROUND & AIMS: It is well-known that the coronary artery stenosis is related to lipid profile. This is a descriptive cross-sectional study to investigate the relationship between the serum fat-soluble vitamins (A, E and D), circulating proprotein convertase subtilisin/kexin type 9 (PCSK9), and lipid profile in the study population. METHODS: A total of 120 overweight subjects were participated in this study. The circulating PCSK9 and vitamin D were measured by ELISA technique. The serum vitamin A and vitamin E amounts were simultaneously measured by the HPLC method. The Serum Small Dense LDLCholesterol (sdLDL-C) values were evaluated using heparin-Mg2+ precipitation technique. The lipid profile was measured by routine laboratory techniques. RESULTS: The serum vitamin E values correlated significantly to vitamin A (r= 0.47, P= 0.0001), VLDL-C (r= 0.30, P= 0.002), total cholesterol (r= 0.309, P= 0.001), PCSK9 (r= 0.233, P= 0.01) and total triglyceride (r= 0.61, P= 0.0001) values. The circulating PCSK9 values correlated significantly to LDL-C (r= 0.17, P= 0.05) and total cholesterol (r= 0.23, P= 0.009) values. However, there were not correlations between the levels of serum D and A vitamins, the serum LDL-C, sdLDL-C and total cholesterol values. CONCLUSION: The data showed the correlations between serum vitamin E and PCSK9-related LDLC values lower than the normal range. Furthermore, the results suggested a nutritional need on the patents considering supplementation or fortification of vitamin E for the overweight subjects with higher LDL-C levels.

Circulating PCSK9 affects serum LDL and cholesterol levels more than SREBP-2 expression.

BACKGROUND: Cholesterol homeostasis is dependent upon the sterol regulatory element binding protein 2 (SREBP-2) regulatory system and the functioning of plasma proprotein convertase subtilisin/kexin type 9 (PCSK9). Many studies have also reported that low density lipoprotein receptor (LDLR) levels in cellular membranes are related to the functioning of these proteins. OBJECTIVES: The aim of this study was to investigate the association of lipid profiles with circulating PCSK9 protein values and SREBP-2 expression levels in normal subjects. MATERIAL AND METHODS: The study involved 120 randomly chosen healthy subjects. Their lipid profiles were measured using routine laboratory techniques, and the plasma PCSK9 protein and SREBP-2 expression levels were determined by ELISA and real time quantitative PCR methods, respectively. A statistical analysis was carried out using a statistical software package. RESULTS: Linear regression analyses showed a significant correlation between total cholesterol and PCSK9 (3.54 ± 1.31 ng/mL), as well as between total cholesterol and SREBP-2 (0.1-35.38) (p = 0.002 and p = 0.02, respectively). Furthermore, multiple regression analyses showed strict correlations between PCSK9 and cholesterol-related parameters especially the total cholesterol/HDL-C ratio (ß = 3.53, p = 0.001). There was no significant correlation between circulating PCSK9 and SREBP-2 expression levels (r = 1.2, p = 0.3). CONCLUSIONS: The study results revealed that serum cholesterol-related parameters are strictly associated with plasma PCSK9 values, suggesting that PCSK9 function has a greater effect on serum total cholesterol levels than SREBP-2 expression does. Furthermore, the total cholesterol/HDL-C ratio was a better indicator for evaluating PCSK9 level than total cholesterol.

Serum sdLDL-C and Cellular SREBP2-dependent Cholesterol Levels; is there a Challenge on Targeting PCSK9?

BACKGROUND: Serum small dense LDL-cholesterol (sdLDL-C) value is suggested to bean important risk factor for atherosclerosis. Since sdLDL-C changes may be related to PCSK9 and SREBP-2 functions, the aim of this study was to investigate correlations between sdLDL-C, circulating PCSK9, SREBP-2 expression and some lipid parameters in serum and butty coat fraction of healthy subjects. METHODS: One hundred and twenty-four subjects were randomly included in the study. The lipid profile was measured using routine laboratory methods. The serum sdLDL-C level was calculated by a heparin-related precipitation technique. The cellular LDL-C/protein and cholesterol/protein values were measured after lysing of cells with methanol/chloroform binary solvent. The circulating PCSK9 level was measured using ELISA technique. The SREBP-2 expression level was estimated using theRT-qPCR technique. RESULTS: Data showed significant correlations between LDL-C, TG and sdLDL-C levels (r=0.34, p=0.001; r=0.2, p=0.04). The circulating PCSK9 level was correlated to LDL-C (r=0.29, p=0.04), but not to sdLDL-C (r=-0.08, p=0.57). Also, cellular LDL-C value was not related to serum LDL-C level (r=-0.12, p=0.39). Furthermore, there was an inverse correlation between cellular LDL-C/protein value and estimated de novo cholesterol/protein value (r= -0.5, p=0.001). Similar results were observed for cellular LDL-C/protein value and SREBP-2 expression level (r= -0.52, p=0.004). CONCLUSIONS: We concluded that the serum sdLDL-C value is not related to circulating PCSK9. Furthermore, SREBP-2 regulatory system was able to elevate the cellular cholesterol level after reducing LDL influx. We suggest to investigate the cellular sdLDL fate and lipid synthesis pathways in PCSK9-targeting studies.