Nanomaterials (NMs) are particles with at least one dimension between 1 and 100 nm and a large surface area to volume ratio, providing them with exceptional qualities that are exploited in a variety of industrial fields. Deposition of NMs into environmental waters during or after use leads to the adsorption of an ecological (eco-) corona, whereby a layer of natural biomolecules coats the NM changing its stability, identity and ultimately toxicity. The eco-corona is not currently incorporated into ecotoxicity tests, although it has been shown to alter the interactions of NMs with organisms such as Daphnia magna (D. magna). Here, the literature on environmental biomolecule interactions with NMs is synthesized and a framework for understanding the eco-corona composition and its role in modulating NMs ecotoxicity is presented, utilizing D. magna as a model. The importance of including biomolecules as part of the current international efforts to update the standard testing protocols for NMs, is highlighted. Facilitating the formation of an eco-corona prior to NMs ecotoxicity testing will ensure that signaling pathways perturbed by the NMs are real rather than being associated with the damage arising from reactive NM surfaces "acquiring" a corona by pulling biomolecules from the organism's surface.novel and unique qualities that are not traditionally exhibited by bulk material of the same composition. NMs have been at the core of novel research for two decades and are incorporated into products spanning a range of industrial fields. For example, NMs properties are exploited in cancer research, such as the utilization of surface plasmon resonance properties of gold (Au) NMs; here the NMs are conjugated to antibodies complementary to antigens on cancer cells and are thereby internalized, following which oscillation of the Au electron cloud at a specific wavelength of light converts the absorbed light into localized heat to specifically destroy cancer cells. [1] Another example is exploitation of the antimicrobial properties of silver (Ag) NMs which undergo high dissolution to release Ag + ions [2] and where the dissolution site, rate (and thus toxicity) can be adjusted depending on the surface coating. [3] Considering that NMs are becoming so widely used, their release into the environment is inevitable. Despite this, considerably less research has focused on the implications of NMs on environmental organisms, especially under realistic conditions, than on development of their applications. NMs may enter freshwater systems from industrial effluent, where, for example, the concentrations of zinc oxide (ZnO) NMs, widely used in sunscreens and paints, in river waters has been found to be as high as 150 ng L −1 , [4] while gold (Au) NMs excreted following use in medical applications into surface waters have been predicted to be 470 pg L −1 [5] With deposition of NMs into environmental waters increasing, concerns regarding the potential for toxicity posed by NMs have demanded action, although the standard testing approaches h...
The redeployed drug combination of bezafibrate and medroxyprogesterone acetate (designated BaP) has potent in vivo anticancer activity in acute myelogenous leukemia (AML) and endemic Burkitt lymphoma (eBL) patients; however, its mechanism-of-action is unclear. Given that elevated fatty acid biosynthesis is a hallmark of many cancers and that these drugs can affect lipid metabolism, we hypothesized that BaP exerts anticancer effects by disrupting lipogenesis. We applied mass spectrometry-based lipidomics and gene and protein expression measurements of key lipogenic enzymes [acetyl CoA carboxylase 1 (ACC1), fatty acid synthase (FASN), and stearoyl CoA desaturase 1 (SCD1)] to AML and eBL cell lines treated with BaP. BaP treatment decreased fatty acid and phospholipid biosynthesis from 13 C D-glucose. The proportion of phospholipid species with saturated and monounsaturated acyl chains was also decreased after treatment, whereas those with polyunsaturated chains increased. BaP decreased SCD1 protein levels in each cell line (0.46-to 0.62-fold; P < 0.023) and decreased FASN protein levels across all cell lines (0.87-fold decrease; P ¼ 1.7 Â 10 À4 ). Changes to ACC1 protein levels were mostly insignificant. Supplementation with the SCD1 enzymatic product, oleate, rescued AML and e-BL cells from BaP cell killing and decreased levels of BaP-induced reactive oxygen species, whereas supplementation with the SCD1 substrate (and FASN product), palmitate, did not rescue cells. In conclusion, these data suggest that the critical anticancer actions of BaP are decreases in SCD1 levels and monounsaturated fatty acid synthesis. To our knowledge, this is the first time that clinically available antileukemic and antilymphoma drugs targeting SCD1 have been reported. Cancer Res; 75(12); 2530-40. Ó2015 AACR.
Lipids play a significant role in regulation of health and disease. To enhance our understanding of the role of lipids in regulation of lifespan and healthspan additional studies are required. Here, UHpLc-MS/ MS lipidomics was used to measure dynamic changes in lipid composition as a function of age and gender in genetically identical male and female Daphnia magna with different average lifespans. We demonstrate statistically significant age-related changes in triglycerides (TG), diglycerides (DG), phosphatidylcholine, phosphatidylethanolamine, ceramide and sphingomyelin lipid groups, for example, in males, 17.04% of TG lipid species decline with age whilst 37.86% increase in relative intensity with age. In females, 23.16% decrease and 25.31% increase in relative intensity with age. Most interestingly, the rate and direction of change can differ between genetically identical female and male Daphnia magna, which could be the cause and/or the consequence of the different average lifespans between the two genetically identical genders. this study provides a benchmark dataset to understand how lipids alter as a function of age in genetically identical female and male species with different average lifespan and ageing rate.
<p>Mass spectrometry data: glycerol 3-phosphate and glycerolipids</p>
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