Factors Influencing the Oxidation of Lipoproteins and Plasma Lipids

The hypothesis that antioxidant vitamins (ascorbate and tocopherols) along with urate protect blood plasma lipids from oxidation was tested. Dietary fat is also an important factor influencing plasma lipid peroxidation. The purpose of this study was to investigate the role of plasma antioxidants and dietary fat on low density lipoprotein (LDL) and plasma lipid oxidation. In the first part of this study, we compared the ability of urate and ascorbate to protect human LDL from in vitro oxidation. LDL oxidation was initiated by 15 mM of a water soluble azo-initiator in the presence or absence of ascorbate or urate. The rate of lipid hydroperoxide (LOOH) formation was increased after the LDL tocopherols were totally consumed, i.e., after the lag phase. Urate (50 $\mu$M) was more effective than ascorbate (50 $\mu$M) in extending the lag phase. Moreover, urate was consumed more slowly than ascorbate under identical oxidation conditions. The combination af 25 $\mu$M ascorbate and 25 $\mu$M urate was more effective in extending the lag phase than ascorbate alone but less effective than urate alone. An empirical mathematical model was developed to describe the oxidation kinetics of LDL tocopherols. In the second part of this study, we studied the role of dietary fat and dietary $\alpha$-tocopherol ($\alpha$-toc) levels on rat plasma oxidation. The fatty acid composition of plasma was found to be modulated by the type of dietary fat. Neither dietary fat nor $\alpha$-toc influenced the plasma levels of water soluble antioxidants (ascorbate, urate and sulfhydryl content). Rat plasma was oxidized either by a water soluble azo-initiator (25 mM) or a lipid soluble azo-initiator (10 mM). In both cases, the rate of LOOH formation in plasma from rats fed butter oil diets was markedly suppressed compared to the plasma from rats fed corn oil diets. When oxidation was initiated by a lipid soluble azo-initiator, plasma from rats fed $\alpha$-toc supplemented diets showed higher LOOH levels than plasma from rats fed $\alpha$-toc deficient diets. Surprisingly, when oxidation was initiated by water soluble azo-initiator, tocopherol appeared to act as a pro-oxidant. The results suggest that urate may be more significant than ascorbate in delaying the consumption of tocopherols in human LDL and that low dietary PUFAs levels are more important in preventing the in vitro oxidation of plasma lipids than high dietary levels of $\alpha$-tocopherol

IRE1α promotes cell apoptosis and an inflammatory response in endoplasmic reticulum stress-induced rheumatoid arthritis fibroblast-like synovial cells by enhancing autophagy

Endoplasmic reticulum (ER) stress can induce autophagy via the unfolded protein response (UPR), and autophagy can regulate the activation of inflammasomes. Inositol-requiring enzyme 1α (IRE1α) is a transducer of the UPR in cells with ER stress. Here, we investigated the role of IRE1α and its impact on ER stress in rheumatoid arthritis fibroblast-like synovial cells (RA-FLSs). RA-FLSs were isolated from rheumatoid arthritis (RA) patients and stimulated with thapsigargin (TG) to produce ER stress cells. ER stress-, autophagy and the expression of apoptosis-associated factors were investigated by western blotting and the qRT-PCR. Cellular ROS levels were assessed by flow cytometry. ELISAs were performed to determine the concentrations of inflammatory mediators. TG treatment promoted IRE1α, GRP78, CHOP, and ATP6 mRNA and protein expression. ROS generation was increased in TG-induced RA-FLSs; additionally, TG was found to induce cell inflammation by upregulating the expression of inflammasome markers and the concentrations of inflammatory mediators. The levels of autophagy markers, apoptosis-associated proteins, and mRNA were increased in TG-stimulated RA-FLSs. However, transfection with si-IRE1α suppressed TG-induced increases in ROS generation, inflammation levels, cell apoptosis, and autophagy in RA-FLSs. Treatment with the autophagy activator RAPA attenuated the protective effects of IRE1α silencing on TG-induced RA-FLS apoptosis and inflammatory damage. Our findings showed that in RA-FLSs, IRE1α silencing alleviated ER stress-induced inflammation and apoptosis caused by autophagy

Nicotinamide mononucleotide adenylyltransferase uses its NAD+ substrate-binding site to chaperone phosphorylated Tau.

Funder: Science and Technology Commission of Shanghai Municipality; FundRef: http://dx.doi.org/10.13039/501100003399Funder: Dr. John T. MacDonald Foundation; FundRef: http://dx.doi.org/10.13039/100010239Tau hyper-phosphorylation and deposition into neurofibrillary tangles have been found in brains of patients with Alzheimer's disease (AD) and other tauopathies. Molecular chaperones are involved in regulating the pathological aggregation of phosphorylated Tau (pTau) and modulating disease progression. Here, we report that nicotinamide mononucleotide adenylyltransferase (NMNAT), a well-known NAD+ synthase, serves as a chaperone of pTau to prevent its amyloid aggregation in vitro as well as mitigate its pathology in a fly tauopathy model. By combining NMR spectroscopy, crystallography, single-molecule and computational approaches, we revealed that NMNAT adopts its enzymatic pocket to specifically bind the phosphorylated sites of pTau, which can be competitively disrupted by the enzymatic substrates of NMNAT. Moreover, we found that NMNAT serves as a co-chaperone of Hsp90 for the specific recognition of pTau over Tau. Our work uncovers a dedicated chaperone of pTau and suggests NMNAT as a key node between NAD+ metabolism and Tau homeostasis in aging and neurodegeneration

An Image Fusion Method Based on Curvelet Transform and Guided Filter Enhancement

In order to improve the clarity of image fusion and solve the problem that the image fusion effect is affected by the illumination and weather of visible light, a fusion method of infrared and visible images for night-vision context enhancement is proposed. First, a guided filter is used to enhance the details of the visible image. Then, the enhanced visible and infrared images are decomposed by the curvelet transform. The improved sparse representation is used to fuse the low-frequency part, while the high-frequency part is fused with the parametric adaptation pulse-coupled neural networks. Finally, the fusion result is obtained by inverse transformation of the curvelet transform. The experimental results show that the proposed method has good performance in detail processing, edge protection, and source image information

Surface Plasmon Resonance Detection of Transgenic Cry1Ac Cotton (Gossypium spp.)

The detection and identification of genetically modified (GM) plants are challenging issues that have arisen from the potential negative impacts of extensive cultivation of transgenic plants. The screening process is a long-term focus and needs specific detection strategies. Surface plasmon resonance (SPR) has been used to detect a variety of biomolecules including proteins and nucleic acids due to its ability to monitor specific intermolecular interactions. In the present study, two high-throughput, label-free, and specific methods based on SPR technology were developed to detect transgenic CrylAc cotton (Gossypium spp.) by separately targeting protein and DNA. In the protein-based detection system, monoclonal anti-Cry1Ac antibodies were immobilized on the surface of a CMS sensor chip. Conventional cotton samples were used to define the detection threshold. Transgenic cotton was easily identified within 5 min per sample. For the DNA-based model, a 25-mer biotinylated oligonucleotide probe was immobilized on an SA sensor chip. PCR products of CrylAc (230 bp) were used to investigate the reaction conditions. The sensitivity of the constructed sensor chip was identified at concentrations as low as 0.1 nM based on its complementary base pairing

The Effects of Dietary α-Tocopherol and Polyunsaturated Fat on Modulating Ischemia-Reperfusion Injury

We investigated the effects of dietary α-tocopherol and polyunsaturated fatty acids (PUFA) on ischemia-reperfusion injury and cardiac lipid composition. Rats were fed corn oil (CO) diets either deficient (CO - E) or supplemented (CO + E) with RRR-α-tocopherol (100 IU kg-1 diet), or butter oil (BO) diets either deficient (BO - E) or supplemented (BO + E) with RRR-α-tocopherol (100 IU kg-1 diet). Intact rat hearts were subjected to ischemia before reperfusion. Dietary RRR-α-tocopherol supplementation contributed to recovery of aortic output, cardiac output and diastolic pressure after ischemia-reperfusion. In contrast, the type of dietary fat did not influence most measures of cardiac recovery. RRR-α-tocopherol levels in cardiac tissues and plasma were significantly higher for rats fed the BO + E diet than for rats fed the CO + E diet. In contrast to plasma, PUFA in cardiac tissues were maintained at a high level even when rats were fed BO containing diets. Our results suggest that dietary RRR-α-tocopherol, but not dietary PUFA levels, modulate oxidative damage to intact rat hearts during ischemia-reperfusion

Pioglitazone Ameliorates Atorvastatin-Induced Islet Cell Dysfunction through Activation of FFA1 in INS-1 Cells

Increasing evidence shows that statins increase the risk of new-onset diabetes mellitus, but the exact mechanism is not clearly known. Free fatty acid receptor 1 (FFA1) has been recognized to mediate insulin secretion, and pioglitazone has direct effects on glucose-stimulated insulin secretion in addition to the reversion of insulin resistance. In this study, we found that atorvastatin decreased potassium-stimulated insulin secretion and inhibited the expression of FFA1, PDX-1, and BETA2/NeuroD in INS-1 cells. Further study demonstrated that pioglitazone prevented the impairment of insulin secretion induced by atorvastatin and enhanced the expression of FFA1, PDX-1, and BETA2/NeuroD reduced by atorvastatin in INS-1 cells. In addition, the preventive effect of pioglitazone on atorvastatin-induced impairment of insulin secretion and the enhancement of the expression of PDX-1 and BETA2/NeuroD was abolished by knockdown of FFA1 using siRNA or the PLC inhibitor, U-73122, respectively. Ultimately, FFA1 may mediate the atorvastatin-induced pancreatic β-cell dysfunction and pioglitazone may ameliorate this deleterious effect through the upregulation of FFA1 expression

Engineering Arsenic Tolerance and Hyperaccumulation in Plants for Phytoremediation by a PvACR3 Transgenic Approach.

Arsenic (As) pollution is a global problem, and the plant-based cleanup of contaminated soils, called phytoremediation, is therefore of great interest. Recently, transgenic approaches have been designed to develop As phytoremediation technologies. Here, we used a one-gene transgenic approach for As tolerance and accumulation in Arabidopsis thaliana. PvACR3, a key arsenite [As(III)] antiporter in the As hyperaccumulator fern Pteris vittata, was expressed in Arabidopsis, driven by the CaMV 35S promoter. In response to As treatment, PvACR3 transgenic plants showed greatly enhanced tolerance. PvACR3 transgenic seeds could even germinate and grow in the presence of 80 mu M As(III) or 1200 mu M arsenate [As(V)] treatments that were lethal to wildtype seeds. PvACR3 localizes to the plasma membrane in Arabidopsis and increases arsenite efflux into external medium in short-term experiments. Arsenic determination showed that PvACR3 substantially reduced As concentrations in roots and simultaneously increased shoot As under 150 mu M As(V). When cultivated in As(V)-containing soil (10 ppm As), transgenic plants accumulated approximately 7.5-fold more As in above-ground tissues than wild-type plants. This study provides important insights into the behavior of PvACR3 and the physiology of As metabolism in plants. Our work also provides a simple and practical PvACR3 transgenic approach for engineering As-tolerant and -hyperaccumulating plants for phytoremediation