Background: Mycobacterium tuberculosis ESAT-6 (MtbESAT-6) is required for phagosomal rupture and bacterial cytosolic translocation.Results: MtbESAT-6 underwent a pH-dependent conformational change and induced leakage of membrane vesicles, while its ortholog from non-pathogenic Mycobacterium smegmatis, MsESAT-6, did not. Conclusion: MtbESAT-6 possesses a unique membrane-interacting activity that is not found in MsESAT-6. Significance: This study links membrane-interacting activity of ESAT-6 to virulence of M. tuberculosis.
Sphingolipids are sphingosine-based phospholipids, which are present in the plasma and endomembranes of many eukaryotic cells. These lipids are involved in various cellular functions, including cell growth, differentiation, and apoptosis. In addition, sphingolipid and cholesterol-enriched membrane microdomains (also called “lipid rafts”) contain a set of proteins and lipids, which take part in the signaling process in response to intra- or extracellular stimuli. Recent findings suggest that sphingolipids, especially glucosylceramide, play a critical role in inducing encystation and maintaining the cyst viability in Giardia. Similarly, the assembly/disassembly of lipid rafts modulates the encystation and cyst production of this ubiquitous enteric parasite. In this review article, we discuss the overall progress in the field and examine whether sphingolipids and lipid rafts can be used as novel targets for designing therapies to control infection by Giardia, which is rampant in developing countries, where children are especially vulnerable.
Obesity is one of the leading public health problems that can result in life-threatening metabolic and chronic diseases such as cardiovascular diseases, diabetes, and cancer. Sorghum (Sorghum bicolor (L.) Moench) is the fifth most important cereal crop in the world and certain genotypes of sorghum have high polyphenol content. PI570481, SC84, and commercially available sumac sorghum are high-polyphenol genotypes that have demonstrated strong anti-cancer activities in previous studies. The objective of this study was to explore a potential anti-obesity use of extracts from sorghum bran in the differentiation of 3T3-L1 preadipocytes and to investigate cellular and molecular responses in differentiated adipocytes to elucidate related mechanisms. None of the four different sorghum bran extracts (PI570481, SC84, Sumac, and white sorghum as a low-polyphenol control) caused cytotoxicity in undifferentiated and differentiated 3T3-L1 cells at doses used in this study. Sorghum bran extracts (PI570481, SC84, and Sumac) reduced intracellular lipid accumulation and expression of adipogenic and lipogenic proteins in a dose-dependent manner in differentiated 3T3-L1 cells. The same polyphenol containing sorghum bran extracts also repressed production of reactive oxygen species (ROS) and MAPK signaling pathways and repressed insulin signaling and glucose uptake in differentiated 3T3-L1 cells. These data propose a potential use of high-phenolic sorghum bran for the prevention of obesity.
Objectives 1) To evaluate the changes in inflammatory response induced by sorghum polyphenols in activated macrophages and 2) to evaluate possible efficacy of sorghum polyphenols on an opportunistic intracellular pathogen, Legionella pneumophila (LP). Methods Raw 265.7 cells mouse macrophage cells were treated with sorghum phenolic extract (SPE) under control and activating conditions to evaluate the role of SPE in inflammatory and anti-inflammatory processes. Study measured: nitric oxide production in the supernatant, mRNA using qPCR array of 84 genes in activated macrophages. Morphological changes were observed, and LC3 protein expression was measured to test for autophagy using western blot. NF-kB and STAT3 nuclear translocation was measured using a fractionization kit, followed by western blot. The replication of LP was measured within RAW 264.7 cells and in vitro (in media without cell presence). Cytotoxicity assay and a western blot apoptosis marker caspase-3 were used to evaluate the cytotoxicity of SPE on RAW 264.7 cells. Because LP reproduction within cells is greatly attenuated in the presence of Tumor Necrosis Factor (TNF), LP replication was measured under the presence of TNF neutralizing antibodies. Results SPE decreased nitric oxide production in activated LPS/IFNΥ macrophages although not significantly. SPE attenuated Th2 cytokine response in LPS/IFNΥ activated macrophages by decreasing expression of IL-6 and IL-10 while not changing expression of other inflammatory cytokines. Quantitative PCR data confirmed that genes in the IL-10 and IL-6 pathway were downregulated by cotreatment of SPE and LPS/IFNΥ when compared to LPS/IFNΥ alone. Morphological changes observed exhibited formation of large vacuole like structures. Analysis of LC3 confirmed that autophagy was increased in activated cells treated with SPE. Nuclear fractionization confirmed that STAT3 signaling was attenuated by SPE in activated macrophages. SPE significantly reduced the replication of LP in macrophage cells but not in vitro. The attenuation of LP grown in RAW 264.7 cells was independent of TNF presence. Conclusions This data suggests that sorghum phenolic compounds may have potential pharmaceutical/nutritional uses to combat intracellular pathogens. Funding Sources All funding was provided by the United States Department of Agriculture.
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