Atherosclerosis, which underlies life-threatening cardiovascular disorders including myocardial infarction and stroke 1 , is initiated by low density lipoprotein cholesterol (LDL) passage into the artery wall and engulfment by macrophages, leading to foam cell formation and lesion development 2, 2, 3, 3 . How circulating LDL enters the artery wall to instigate atherosclerosis is unknown. Here we show in mice that scavenger receptor, class B type 1 (SR-B1) in endothelial Reprints and permissions information is available at www.nature.com/reprints.Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:
Programmed cell death (PCD) is a key element in normal plant growth and development which may also be induced by various abiotic and biotic stress factors including salt stress. In the present study, morphological, biochemical, and physiological responses of the theoretically immortal unicellular freshwater green alga Micrasterias denticulata were examined after salt (200 mM NaCl or 200 mM KCl) and osmotic stress induced by iso-osmotic sorbitol. KCl caused morphological changes such as cytoplasmic vacuolization, extreme deformation of mitochondria, and ultrastructural changes of Golgi and ER. However, prolonged salt stress (24 h) led to the degradation of organelles by autophagy, a special form of PCD, both in NaCl- and KCl-treated cells. This was indicated by the enclosure of organelles by ER-derived double membranes. DNA of NaCl- and KCl-stressed cells but not of sorbitol-treated cells showed a ladder-like pattern on agarose gel, which means that the ionic rather than the osmotic component of salt stress leads to the activation of the responsible endonuclease. DNA laddering during salt stress could be abrogated by addition of Zn2+. Neither cytochrome c release from mitochondria nor increase in caspase-3-like activity occurred after salt stress. Reactive oxygen species could be detected within 5 min after the onset of salt and osmotic stress. Respiration, photosynthetic activity, and pigment composition indicated an active metabolism which supports programmed rather than necrotic cell death in Micrasterias after salt stress.
BackgroundAltered lipid metabolism is an emerging hallmark of aggressive breast cancers. The N-myc downstream regulated gene (NDRG1) gene plays a critical role in peripheral nervous system myelination, as inactivating mutations cause severe demyelinating neuropathy. In breast cancer, elevated NDRG1 expression has been linked to clinical outcomes, but its functional role in breast cancer physiology has remained unclear.MethodsA meta-analysis of NDRG1 expression in multiple large publicly available genomic databases was conducted. Genome-wide expression correlation and Cox proportional hazards and Kaplan-Meier modeling of clinical outcomes associated with elevated expression were assessed. To study NDRG1 function, gene silencing and overexpression phenotypic studies were carried out in a panel of cell lines representing all major breast cancer molecular subtypes. Changes in cell proliferation, morphology, and neutral lipid accumulation due to altered NDRG1 expression were assessed by high throughput, quantitative microscopy. Comprehensive lipidomics mass spectrometry was applied to characterize global changes in lipid species due to NDRG1 silencing. Labeled fatty acids were used to monitor cellular fatty acid uptake and subcellular distribution under nutrient replete and starvation culture conditions.ResultsNDRG1 overexpression correlated with glycolytic and hypoxia-associated gene expression, and was associated with elevated rates of metastasis and patient mortality. Silencing NDRG1 reduced cell proliferation rates, causing lipid metabolism dysfunction including increased fatty acid incorporation into neutral lipids and lipid droplets. Conversely, NDRG1 expression minimized lipid droplet formation under nutrient replete and starvation conditions.ConclusionsHere we report that NDRG1 contributes to breast cancer aggressiveness by regulating the fate of lipids in cells that exhibit an altered lipid metabolic phenotype. In line with its role in promoting myelination and its association with altered metabolism in cancer, our findings show that NDRG1 is a critical regulator of lipid fate in breast cancer cells. The association between NDRG1 and poor prognosis in breast cancer suggests it should play a more prominent role in patient risk assessment. The function of NDRG1 in breast cancer lipid metabolism may represent a promising therapeutic approach in the future.Electronic supplementary materialThe online version of this article (10.1186/s13058-018-0980-4) contains supplementary material, which is available to authorized users.
Carbon export from leaf mesophyll to sugar-transporting phloem occurs via either an apoplastic (across the cell membrane) or symplastic (through plasmodesmatal cell wall openings) pathway. Herbaceous apoplastic loaders generally exhibit an up-regulation of photosynthetic capacity in response to growth at lower temperature. However, acclimation of photosynthesis to temperature by symplastically loading species, whose geographic distribution is particularly strong in tropical and subtropical areas, has not been characterized. Photosynthetic and leaf anatomical acclimation to lower temperature was explored in two symplastic (Verbascum phoeniceum, Cucurbita pepo) and two apoplastic (Helianthus annuus, Spinacia oleracea) loaders, representing summer- and winter-active life histories for each loading type. Regardless of phloem loading type, the two summer-active species, C. pepo and H. annuus, exhibited neither foliar anatomical nor photosynthetic acclimation when grown under low temperature compared to moderate temperature. In contrast, and again irrespective of phloem loading type, the two winter-active mesophytes, V. phoeniceum and S. oleracea, exhibited both a greater number of palisade cell layers (and thus thicker leaves) and significantly higher maximal capacities of photosynthetic electron transport, as well as, in the case of V. phoeniceum, a greater foliar vein density in response to cool temperatures compared to growth at moderate temperature. It is therefore noteworthy that symplastic phloem loading per se does not prevent acclimation of intrinsic photosynthetic capacity to cooler growth temperatures. Given the vagaries of weather and climate, understanding the basis of plant acclimation to, and tolerance of, low temperature is critical to maintaining and increasing plant productivity for food, fuel, and fiber to meet the growing demands of a burgeoning human population.
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