Plasmalogens the neglected regulatory and scavenging lipid species

Plasmalogens are a class of phospholipids carrying a vinyl ether bond in sn-1 and an ester bond in sn-2 position of the glycerol backbone. Although they are widespread in all tissues and represent up to 18% of the total phospholipid mass in humans, their physiological function is still poorly understood. The aim of this review is to give an overview over the current knowledge in plasmalogen biology and pathology with an emphasis on neglected aspects of their involvement in neurological and metabolic diseases. Furthermore a better understanding of plasmalogen biology in health and disease could also lead to the development of better diagnostic and prognostic biomarkers for vascular and metabolic diseases such as obesity and diabetes mellitus, inflammation, neuro-degeneration and cancer.     

Docosahexaenoic acid synthesis from alpha-linolenic acid is inhibited by diets high in polyunsaturated fatty acids

The conversion of the plant-derived omega-3 (n-3) α-linolenic acid (ALA, 18:3n-3) to the long-chain eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) can be increased by ALA sufficient diets compared to ALA deficient diets. Diets containing ALA above an optimal level result in no further increase in DHA levels in animals and humans. The present study evaluates means of maximizing plasma DHA accumulation by systematically varying both linoleic acid (LA, 18:2n-6) and ALA dietary level. Weanling rats were fed one of 54 diets for three weeks. The diets varied in the percentage of energy (en%) of LA (0.07–17.1 en%) and ALA (0.02–12.1 en%) by manipulating both the fat content and the balance of vegetable oils. The peak of plasma phospholipid DHA (>8% total fatty acids) was attained as a result of feeding a narrow dietary range of 1–3 en% ALA and 1–2 en% LA but was suppressed to basal levels (～2% total fatty acids) at dietary intakes of total polyunsaturated fatty acids (PUFA) above 3 en%. We conclude it is possible to enhance the DHA status of rats fed diets containing ALA as the only source of n-3 fatty acids but only when the level of dietary PUFA is low (<3 en%).     

Docosapentaenoic acid (22:5n-3): A review of its biological effects

This article summarizes the current knowledge available on metabolism and the biological effects of n-3 docosapentaenoic acid (DPA). n-3 DPA has not been extensively studied because of the limited availability of the pure compound. n-3 DPA is an elongated metabolite of EPA and is an intermediary product between EPA and DHA. The literature on n-3 DPA is limited, however the available data suggests it has beneficial health effects. In vitro n-3 DPA is retro-converted back to EPA, however it does not appear to be readily metabolised to DHA. In vivo studies have shown limited conversion of n-3 DPA to DHA, mainly in liver, but in addition retro-conversion to EPA is evident in a number of tissues. n-3 DPA can be metabolised by lipoxygenase, in platelets, to form ll-hydroxy-7,9,13,16,19- and 14-hydroxy-7,10,12,16,19-DPA. It has also been reported that n-3 DPA is effective (more so than EPA and DHA) in inhibition of aggregation in platelets obtained from rabbit blood. In addition, there is evidence that n-3 DPA possesses 10-fold greater endothelial cell migration ability than EPA, which is important in wound-healing processes. An in vivo study has reported that n-3 DPA reduces the fatty acid synthase and malic enzyme activity levels in n-3 DPA-supplemented mice and these effects were stronger than the EPA-supplemented mice. Another recent in vivo study has reported that n-3 DPA may have a role in attenuating age-related decrease in spatial learning and long-term potentiation. However, more research remains to be done to further investigate the biological effects of this n-3 VLCPUFA.     

Essential role of ERK activation in neurite outgrowth induced by α-lipoic acid

Background

Neurite outgrowth is an important aspect of neuronal plasticity and regeneration after neuronal injury. Alpha-lipoic acid (LA) has been used as a therapeutic approach for a variety of neural disorders. We recently reported that LA prevents local anesthetics-induced neurite loss. In this study, we hypothesized that LA administration promotes neurite outgrowth.

Methods

To test our hypothesis, we treated mouse neuroblastoma N2a cells and primary neurons with LA. Neurite outgrowth was evaluated by examination of morphological changes and by immunocytochemistry for β-tubulin-3. ROS production was examined, as were the phosphorylation levels of ERK and Akt. In separate experiments, we determined the effects of the inhibition of ERK or PI3K/Akt as well as ROS production on LA-induced neurite outgrowth.

Results

LA promoted significantly neurite outgrowth in a time- and concentration-dependent manner. LA stimulation significantly increased the phosphorylation levels of both Akt and ERK and transiently induced ROS production. PI3K/Akt inhibition did not affect LA-induced neurite outgrowth. However, the inhibition of ERK activation completely abolished LA-induced neurite outgrowth. Importantly, the prevention of ROS production by antioxidants attenuated LA-stimulated ERK activation and completely abolished LA-promoted neurite outgrowth.

Conclusion

Our data suggest that LA stimulates neurite outgrowth through the activation of ERK signaling, an effect mediated through a ROS-dependent mechanism.     

Ascorbate-glutathione cycle of mitochondria in osmoprimed soybean cotyledons in response to imbibitional chilling injury

Osmopriming treatment of chilling-sensitive soybean (Glycine max L. cv. Zhonghuang-22) seeds for 72 h at 25 °C with polyethylene glycol (PEG8000) solution at −1.5 MPa strongly improves chilling resistance. The aim of the present work was to investigate whether the beneficial effect of osmopriming is associated with restoration of the ascorbate-glutathione (ASC-GSH) cycle of mitochondria in soybean seeds. Compared with the control, both H₂O₂ and malondialdehyde (MDA) contents in mitochondria of osmoprimed seeds decreased after chilling treatment, and these changes were associated with increased activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), glutathione reductase (GR), monodehydroascorbate reductase (MDHAR) and l-galactono-γ-lactone dehydrogenase (GLDH). However, the activity of dehydroascorbate reductase (DHAR) showed no obvious change during osmopriming treatment. Increased ASC and GSH contents accompanied prolonged osmopriming, and the reduced/oxidized ratios of ASC and GSH increased differently during osmopriming. These results indicate that osmopriming treatment enhances activity of the ASC-GSH cycle of mitochondria, which raises the chilling tolerance in soybean seeds and protects against H₂O₂ that is generated in mitochondria during imbibition at low temperature.     

Beneficial effects of omega-3 long-chain fatty acids in breast cancer and cardiovascular diseases: voltage-gated sodium channels as a common feature?

Cancers are among the leading causes of death worldwide. Voltage-gated sodium channels, among other ion channels, appear as new molecular players in epithelial cancers. Highly metastatic breast cancer cells express Na_V1.5, the main isoform expressed in cardiac cells, where the current generated by the flux of sodium ions is responsible for the excitability. Breast cancer cells are not excitable and the protein activity regulates cell invasiveness, through the modulation of activity of acidic cathepsins, a characteristic involved in the metastatic phenotype. Interestingly, it is known that ω-3 LC-PUFA can exert beneficial effects by preventing post-myocardial infarction arrhythmias and by reducing the incidence of metastatic breast cancer.In this review, we compare the effects of some ω-3 LC-PUFA on Na_V1.5 expressed in both cardiac and MDA-MB-231 breast cancer cells. We propose that some of the effects of ω-3 LC-PUFA act through common mechanisms involved in both diseases.     

Heart arachidonic acid is uniquely sensitive to dietary arachidonic acid and docosahexaenoic acid content in domestic piglets

This study determined the sensitivity of heart and brain arachidonic acid (ARA) and docosahexaenoic acid (DHA) to the dietary ARA level in a dose–response design with constant, high DHA in neonatal piglets. On day 3 of age, pigs were assigned to 1 of 6 dietary formulas varying in ARA/DHA as follows (% fatty acid, FA/FA): (A1) 0.1/1.0; (A2) 0.53/1.0; (A3–D3) 0.69/1.0; (A4) 1.1/1.0; (D2) 0.67/0.62; and (D1) 0.66/0.33. At necropsy (day 28) higher levels of dietary ARA were associated with increased heart and liver ARA, while brain ARA remained unaffected. Dietary ARA had no effect on tissue DHA accretion. Heart was particularly sensitive, with pigs in the intermediate groups having different ARA (A2, 18.6±0.7%; A3, 19.4±1.0%) and a 0.17% increase in dietary ARA resulted in a 0.84% increase in heart ARA. Further investigations are warranted to determine the clinical significance of heart ARA status in developing neonates.