Loss of alkaline ceramidase inhibits autophagy in Arabidopsis and plays an important role during environmental stress response

Sphingolipids, a class of bioactive lipids found in cell membranes, can modulate the biophysical properties of the membranes and play a critical role in signal transduction. Sphingolipids are involved in autophagy in humans and yeast, but their role in autophagy in plants is not well understood. In this study, we reported that the AtACER, an alkaline ceramidase that hydrolyses ceramide to long‐chain base (LCB), functions in autophagy process in Arabidopsis. Our empirical data showed that the loss of AtACER inhibited autophagy, and its overexpression promoted autophagy under nutrient, salinity, and oxidative stresses. Interestingly, nitrogen deprivation significantly affected the sphingolipid's profile in Arabidopsis thaliana, especially the LCBs. Furthermore, the exogenous application of LCBs also induced autophagy. Our findings revealed a novel function of AtACER, where it was found to involve in the autophagy process, thus, playing a crucial role in the maintenance of a dynamic loop between sphingolipids and autophagy for cellular homeostasis under various environmental stresses.     

Highly efficient preparation of sphingoid bases from glucosylceramides by chemoenzymatic method

Sphingoid base derivatives have attracted increasing attention as promising chemotherapeutic candidates against lifestyle diseases such as diabetes and cancer. Natural sphingoid bases can be a potential resource instead of those derived by time-consuming total organic synthesis. In particular, glucosylceramides (GlcCers) in food plants are enriched sources of sphingoid bases, differing from those of animals. Several chemical methodologies to transform GlcCers to sphingoid bases have already investigated; however, these conventional methods using acid or alkaline hydrolysis are not efficient due to poor reaction yield, producing complex by-products and resulting in separation problems. In this study, an extremely efficient and practical chemoenzymatic transformation method has been developed using microwave-enhanced butanolysis of GlcCers and a large amount of readily available almond β-glucosidase for its deglycosylation reaction of lysoGlcCers. The method is superior to conventional acid/base hydrolysis methods in its rapidity and its reaction cleanness (no isomerization, no rearrangement) with excellent overall yield.     

Human gut endogenous proteins as a potential source of angiotensin-I-converting enzyme (ACE-I)-, renin inhibitory and antioxidant peptides

It is well known that endogenous bioactive proteins and peptides play a substantial role in the body's first line of immunological defence, immune-regulation and normal body functioning. Further, the peptides derived from the luminal digestion of proteins are also important for body function. For example, within the peptide database BIOPEP (http://www.uwm.edu.pl/biochemia/index.php/en/biopep) 12 endogenous antimicrobial and 64 angiotensin-I-converting enzyme (ACE-I) inhibitory peptides derived from human milk and plasma proteins are listed. The antimicrobial peptide database (http://aps.unmc.edu/AP/main.php) lists over 111 human host-defence peptides. Several endogenous proteins are secreted in the gut and are subject to the same gastrointestinal digestion processes as food proteins derived from the diet. The human gut endogenous proteins (GEP) include mucins, serum albumin, digestive enzymes, hormones, and proteins from sloughed off epithelial cells and gut microbiota, and numerous other secreted proteins. To date, much work has been carried out regarding the health altering effects of food-derived bioactive peptides but little attention has been paid to the possibility that GEP may also be a source of bioactive peptides. In this review, we discuss the potential of GEP to constitute a gut cryptome from which bioactive peptides such as ACE-I inhibitory, renin inhibitory and antioxidant peptides may be derived.     

Molecular mechanisms of drug resistance and its reversal in cancer

Chemotherapy is the main strategy for the treatment of cancer. However, the main problem limiting the success of chemotherapy is the development of multidrug resistance. The resistance can be intrinsic or acquired. The resistance phenotype is associated with the tumor cells that gain a cross-resistance to a large range of drugs that are structurally and functionally different. Multidrug resistance arises via many unrelated mechanisms, such as overexpression of energy-dependent efflux proteins, decrease in uptake of the agents, increase or alteration in drug targets, modification of cell cycle checkpoints, inactivation of the agents, compartmentalization of the agents, inhibition of apoptosis and aberrant bioactive sphingolipid metabolism. Exact elucidation of resistance mechanisms and molecular and biochemical approaches to overcome multidrug resistance have been a major goal in cancer research. This review comprises the mechanisms guiding multidrug resistance in cancer chemotherapy and also touches on approaches for reversing the resistance.     

Cell regulation by sphingosine and more complex sphingolipids

Sphingolipids have the potential to regulate cell behavior at essentially all levels of signal transduction. They serve as cell surface receptors for cytoskeletal proteins, immunoglobulins, and some bacteria; as modifiers of the properties of cell receptors for growth factors (and perhaps other agents); and as activators and inhibitors of protein kinases, ion transporters, and other proteins. Furthermore, the biological activity of these compounds resides not only in the more complex species (e.g., sphingomyelin, cerebrosides, gangliosides, and sulfatides), but also in their turnover products, such as the sphingosine backbone which inhibits protein kinase C and activates the EGF-receptor kinase,inter alia. Since sphingolipids change with cell growth, differentiation, and neoplastic transformation, they could be vital participants in the regulation of these processes.This review is dedicated to Professor Herbert E. Carter on the occasion of his 80th birthday.     

Algae as production systems of bioactive compounds

Algal extracts are gaining increasing interest due to their unique composition and possibilities of wide industrial applications. Various extraction techniques are used for conversion of algal biomass into extracts. Recently, attention of scientists has been paid to novel methods, such as enzyme‐assisted extraction, microwave‐assisted extraction, pressurized liquid extraction, supercritical fluid extraction, and ultrasound‐assisted extraction, which enable the extraction of biologically active compounds without their degradation. In this review, the properties of biologically active compounds extracted from the biomass of algae reported in the literature are presented in a structured way. Algal extracts contain compounds such as carbohydrates, proteins, minerals, oil, fats, polyunsaturated fatty acids as well as bioactive compounds such as antioxidants (polyphenols, tocopherols [vitamin E], vitamin C, mycosporine‐like amino acids), and pigments, such as carotenoids (carotene xanthophyll), chlorophylls, and phycobilins (phycocyanin, phycoerythrin), which possess antibacterial, antiviral, antifungal, antioxidative, anti‐inflammatory, and antitumor properties. Finally, we assemble a list of applications of algal extracts in different developing branches of agriculture (biostimulants, bioregulators, feed additives) and in pharmaceutical industry.     

Dihydroceramide accumulation mediates cytotoxic autophagy of cancer cells via autolysosome destabilization

Autophagy is considered primarily a cell survival process, although it can also lead to cell death. However, the factors that dictate the shift between these 2 opposite outcomes remain largely unknown. In this work, we used Δ⁹-tetrahydrocannabinol (THC, the main active component of marijuana, a compound that triggers autophagy-mediated cancer cell death) and nutrient deprivation (an autophagic stimulus that triggers cytoprotective autophagy) to investigate the precise molecular mechanisms responsible for the activation of cytotoxic autophagy in cancer cells. By using a wide array of experimental approaches we show that THC (but not nutrient deprivation) increases the dihydroceramide:ceramide ratio in the endoplasmic reticulum of glioma cells, and this alteration is directed to autophagosomes and autolysosomes to promote lysosomal membrane permeabilization, cathepsin release and the subsequent activation of apoptotic cell death. These findings pave the way to clarify the regulatory mechanisms that determine the selective activation of autophagy-mediated cancer cell death.     

肠道菌群代谢产物及酶对骨代谢的影响机制初探

骨质疏松症是一种常见的代谢性骨病,其发病并非是由单一因素引起,而是由多种因素所致。人们生活水平和医疗条件的提高使人们寿命延长导致老龄化现象,对应的骨质疏松症的发病率也处于上升趋势。骨质疏松在全球范围都是一个值得关注的健康问题。骨质疏松的治疗一直以基础治疗为主,包括生活方式干预和基础营养素补充,药物治疗,还有治疗后期的康复训练。但近年来愈来愈多的研究表明骨质疏松症和肠道菌群之间密切相关,因而肠道菌群已成为抗骨质疏松的一个新靶点。本文结合国内外相关文献就骨质疏松是如何受肠道菌群代谢产物及酶的影响作一综述。