scholarly journals Developmentally regulated H2Av buffering via dynamic sequestration to lipid droplets in Drosophila embryos

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Matthew Richard Johnson ◽  
Roxan Amanda Stephenson ◽  
Sina Ghaemmaghami ◽  
Michael Andreas Welte
Keyword(s):  
Lipid Droplets ◽  
Nuclear Accumulation ◽  
Developmentally Regulated ◽  
Midblastula Transition ◽  
Regulatory Strategies ◽  
Developmental Progression ◽  
Mechanistic Basis ◽  
Histone Exchange ◽  
Drosophila Embryos

Regulating nuclear histone balance is essential for survival, yet in early Drosophila melanogaster embryos many regulatory strategies employed in somatic cells are unavailable. Previous work had suggested that lipid droplets (LDs) buffer nuclear accumulation of the histone variant H2Av. Here, we elucidate the buffering mechanism and demonstrate that it is developmentally controlled. Using live imaging, we find that H2Av continuously exchanges between LDs. Our data suggest that the major driving force for H2Av accumulation in nuclei is H2Av abundance in the cytoplasm and that LD binding slows nuclear import kinetically, by limiting this cytoplasmic pool. Nuclear H2Av accumulation is indeed inversely regulated by overall buffering capacity. Histone exchange between LDs abruptly ceases during the midblastula transition, presumably to allow canonical regulatory mechanisms to take over. These findings provide a mechanistic basis for the emerging role of LDs as regulators of protein homeostasis and demonstrate that LDs can control developmental progression.

scholarly journals Author response: Developmentally regulated H2Av buffering via dynamic sequestration to lipid droplets in Drosophila embryos

2018 ◽  
Author(s):  
Matthew Richard Johnson ◽  
Roxan Amanda Stephenson ◽  
Sina Ghaemmaghami ◽  
Michael Andreas Welte
Keyword(s):  
Lipid Droplets ◽  
Author Response ◽  
Developmentally Regulated ◽  
Drosophila Embryos

scholarly journals The dynamic behavior of lipid droplets in the pre-metastatic niche

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Chunliang Shang ◽  
Jie Qiao ◽  
Hongyan Guo
Keyword(s):  
Tumor Cells ◽  
Immune Cells ◽  
Stromal Cells ◽  
Lipid Droplets ◽  
Metastatic Tumor ◽  
Current Evidence ◽  
Biological Functions ◽  
Metastatic Niche ◽  
Niche Formation

AbstractThe pre-metastatic niche is a favorable microenvironment for the colonization of metastatic tumor cells in specific distant organs. Lipid droplets (LDs, also known as lipid bodies or adiposomes) have increasingly been recognized as lipid-rich, functionally dynamic organelles within tumor cells, immune cells, and other stromal cells that are linked to diverse biological functions and human diseases. Moreover, in recent years, several studies have described the indispensable role of LDs in the development of pre-metastatic niches. This review discusses current evidence related to the biogenesis, composition, and functions of LDs related to the following characteristics of the pre-metastatic niche: immunosuppression, inflammation, angiogenesis/vascular permeability, lymphangiogenesis, organotropism, reprogramming. We also address the function of LDs in mediating pre-metastatic niche formation. The potential of LDs as markers and targets for novel antimetastatic therapies will be discussed.

scholarly journals Oncogenic UBE3C promotes breast cancer progression by activating Wnt/β-catenin signaling

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chen Hang ◽  
Shanojie Zhao ◽  
Tiejun Wang ◽  
Yan Zhang
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Nuclear Accumulation ◽  
Migration And Invasion ◽  
Ubiquitin Protein Ligase ◽  
Novel Target ◽  
First Time ◽  
Breast Tissues

Abstract Background Breast cancer (BrCa) is the most common female malignancy worldwide and has the highest morbidity among all cancers in females. Unfortunately, the mechanisms of BrCa growth and metastasis, which lead to a poor prognosis in BrCa patients, have not been well characterized. Methods Immunohistochemistry (IHC) was performed on a BrCa tissue microarray (TMA) containing 80 samples to evaluate ubiquitin protein ligase E3C (UBE3C) expression. In addition, a series of cellular experiments were conducted to reveal the role of UBE3C in BrCa. Results In this research, we identified UBE3C as an oncogenic factor in BrCa growth and metastasis for the first time. UBE3C expression was upregulated in BrCa tissues compared with adjacent breast tissues. BrCa patients with high nuclear UBE3C expression in tumors showed remarkably worse overall survival (OS) than those with low nuclear expression. Knockdown of UBE3C expression in MCF-7 and MDA-MB-453 BrCa cells inhibited cell proliferation, migration and invasion in vitro, while overexpression of UBE3C in these cells exerted the opposite effects. Moreover, UBE3C promoted β-catenin nuclear accumulation, leading to the activation of the Wnt/β-catenin signaling pathway in BrCa cells. Conclusion Collectively, these results imply that UBE3C plays crucial roles in BrCa development and progression and that UBE3C may be a novel target for the prevention and treatment of BrCa.

scholarly journals Identification and developmental regulation of a neuron-specific subunit of cytoplasmic dynein.

1996 ◽  
Vol 7 (2) ◽  
pp. 331-343 ◽  
Author(s):  
K K Pfister ◽  
M W Salata ◽  
J F Dillman ◽  
E Torre ◽  
R J Lye
Keyword(s):  
Axonal Transport ◽  
Developmental Regulation ◽  
Cytoplasmic Dynein ◽  
Retrograde Axonal Transport ◽  
Protein Isoforms ◽  
Cultured Neurons ◽  
Developmentally Regulated ◽  
Time Period ◽  
Intermediate Chains

Cytoplasmic dynein is the microtubule minus-end-directed motor for the retrograde axonal transport of membranous organelles. Because of its similarity to the intermediate chains of flagellar dynein, the 74-kDa intermediate chain (IC74) subunit of dynein is thought to be involved in binding dynein to its membranous organelle cargo. Previously, we identified six isoforms of the IC74 cytoplasmic dynein subunit in the brain. We further demonstrated that cultured glia and neurons expressed different dynein IC74 isoforms and phospho-isoforms. Two isoforms were observed when dynein from glia was analyzed. When dynein from cultured neurons was analyzed, six IC74 isoforms were observed, although the relative amounts of the dynein isoforms from cultured neurons differed from those found in dynein from brain. To better understand the role of the neuronal IC74 isoforms and identify neuron-specific IC74 dynein subunits, the expression of the IC74 protein isoforms and mRNAs of various tissues were compared. As a result of this comparison, the identity of each of the isoform spots observed on two-dimensional gels was correlated with the products of each of the IC74 mRNAs. We also found that between the fifteenth day of gestation (E15) and the fifth day after birth (P5), the relative expression of the IC74 protein isoforms changes, demonstrating that the expression of IC74 isoforms is developmentally regulated in brain. During this time period, there is relatively little change in the abundance of the various IC74 mRNAs. The E15 to P5 time period is one of rapid process extension and initial pattern formation in the rat brain. This result indicates that the changes in neuronal IC74 isoforms coincide with neuronal differentiation, in particular the extension of processes. This suggests a role for the neuronal IC74 isoforms in the establishment or regulation of retrograde axonal transport.

Oxidative Stress and Cancer: The Role of Nrf2

2018 ◽  
Vol 18 (6) ◽  
pp. 538-557 ◽  
Author(s):  
Soraya Sajadimajd ◽  
Mozafar Khazaei
Keyword(s):  
Oxidative Stress ◽  
Cell Fate ◽  
Nuclear Import ◽  
Tyrosine Kinases ◽  
Oxidative Enzymes ◽  
Nuclear Accumulation ◽  
Constitutive Activation ◽  
Number Of Genes ◽  
Electrophilic Stress

Oxidative stress due to imbalance between ROS production and detoxification plays a pivotal role in determining cell fate. In response to the excessive ROS, apoptotic signaling pathway is activated to promote normal cell death. However, through deregulation of biomolecules, high amount of ROS promotes carcinogenesis in cells with defective signaling factors. In this line, NRF2 appears to be as a master regulator, which protects cells from oxidative and electrophilic stress. Nrf2 is an intracellular transcription factor that regulates the expression of a number of genes to encode anti-oxidative enzymes, detoxifying factors, anti-apoptotic proteins and drug transporters. Under normal condition, Nrf2 is commonly degraded in cytoplasm by interaction with Keap1 inhibitor as an adaptor for ubiquitination factors. However, high amount of ROS activates tyrosine kinases to dissociate Nrf2: Keap1 complex, nuclear import of Nrf2 and coordinated activation of cytoprotective gene expression. Nevertheless, deregulation of Nrf2 and/or Keap1 due to mutation and activated upstream oncogenes is associated with nuclear accumulation and constitutive activation of Nrf2 to protect cells from apoptosis and induce proliferation, metastasis and chemoresistance. Owning to the interplay of ROS and Nrf2 signaling pathways with carcinogenesis, Nrf2 modulation seems to be important in the personalization of cancer therapy.

193 Single Cell RNA-sequencing Reveals a Role of Lipid Metabolism in Muscle Satellite Cells

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 104-105
Author(s):  
Shihuan Kuang ◽  
Feng Yue ◽  
Stephanie Oprescu
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Cell Fate ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Lipid Droplets ◽  
Self Renewal ◽  
Droplet Dynamics ◽  
Single Cell Rna Sequencing

Abstract Single Cell RNA-sequencing (scRNA-seq) is a powerful technique to deconvolute gene expression of various subset of cells intermingled within a complex tissue, such as the skeletal muscle. We first used scRNA-seq to understand dynamics of cell populations and their gene expression during muscle regeneration in murine limb muscles. This leads to the identification of a subset of satellite cells (the resident stem cells of skeletal muscles) with immune gene signatures in regenerating muscles. Next, we used scRNA-seq to examine gene expression dynamics of satellite cells at various status: quiescence, activation, proliferation, differentiation and self-renewal. This analysis uncovers stage-dependent changes in expression of genes related to lipid metabolism. Further analyses lead to the discovery of previously unappreciated dynamics of lipid droplets in satellite cells; and demonstrate that the abundance of the lipid droplets in newly divided satellite daughter cells is linked to cell fate segregation into differentiation versus self-renewal. Perturbation of lipid droplet dynamics through blocking lipolysis disrupts cell fate homeostasis and impairs muscle regeneration. Finally, we show that lipid metabolism regulates the function of satellite cells through two mechanisms. On one hand, lipid metabolism functions as an energy source through fatty acid oxidation (FAO), and blockage of FAO reduces energy production that is critical for satellite cell function. On the other hand, lipid metabolism generates bioactive molecules that influence signaling transduction and gene expression. In this scenario, lipid metabolism and FAO regulate the intracellular levels of acetyl-coA and selective acetylation of PAX7, a pivotal transcriptional factor underlying function of satellite cells. These results together reveal for the first time a critical role of lipid metabolism and lipid droplet dynamics in muscle satellite cell fate determination and regenerative function; and underscore a potential role of dietary fatty acids in satellite cell-dependent muscle development, growth and regeneration.

scholarly journals Alleviation of carbon tetrachloride-induced hepatocellular damage and oxidative stress with a leaf extract of Glyphae brevis (Tiliaceae)

2018 ◽  
Vol 29 (6) ◽  
pp. 609-619 ◽  
Author(s):  
Lucky Legbosi Nwidu ◽  
Yibala I. Oboma ◽  
Ekramy Elmorsy ◽  
Wayne Grant Carter
Keyword(s):  
Carbon Tetrachloride ◽  
Leaf Extract ◽  
Protective Role ◽  
Lipid Peroxidation Product ◽  
Hematological Indices ◽  
Hepatocellular Damage ◽  
Antioxidant Parameters ◽  
Mechanistic Basis ◽  
Histopathological Studies

Abstract Background Glyphae brevis leaf is reported in ethnomedicine as a treatment for hepatitis and jaundice; however, no studies have hitherto investigated the mechanistic basis of these claims. Methods A hepato-protective role of G. brevis hydromethanolic (GBH) leaf extract was established against carbon tetrachloride (CCl4)-induced hepatotoxicity. Twenty-four hours after a CCl4 challenge, rats were sacrificed and serum hematological indices, lipid profile, and biochemical parameters were determined. The antioxidant enzymes parameters (glutathione, catalase, and superoxide dismutase) and lipid peroxidation product (thiobarbituric reactive substances) levels in liver homogenates were evaluated. Changes in the liver cyto-architecture of different treatment groups were also investigated. Results The GBH extract produced no significant impact on weight and hematological indices. Intoxication with CCl4 significantly (p<0.001–0.05) increased total cholesterol (TC) and low-density lipoproteins (LDL) compared with control rats. Pretreatment with GBH leaf extract significantly reduced triglycerides, TC, and LDL to approaching control levels (p<0.001–0.05). The GBH leaf extract significantly alleviated CCl4-induced elevation of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and the CCl4-induced depression of total protein, and albumin. Liver antioxidant parameters were significantly increased in plant extract-treated rats, and this antagonized the pro-oxidant effect of CCl4. Histopathological studies also supported a hepato-protective effect of GBH. Collectively, the GBH leaf extract alleviated the CCl4-induced hepatotoxicity through improvement of innate antioxidant enzyme levels and lipid metabolism and stabilized the hepatocyte cyto-architecture of intoxicated rats. Conclusions This study establishes the ethnomedicinal role of G. brevis leaf in hepatitis and the mechanistic basis of hepato-protection against CCl4-induced hepatotoxicity.

scholarly journals Why developmental niche construction is not selective niche construction: and why it matters

2017 ◽  
Vol 7 (5) ◽  
pp. 20160157 ◽  
Author(s):  
Karola Stotz
Keyword(s):  
Niche Construction ◽  
Active Role ◽  
Evolutionary Significance ◽  
Heritable Variation ◽  
Developmentally Regulated ◽  
Diverse Range ◽  
Developmental Niche ◽  
Constructed Environment ◽  
Selective Environment

In the last decade, niche construction has been heralded as the neglected process in evolution. But niche construction is just one way in which the organism's interaction with and construction of the environment can have potential evolutionary significance. The constructed environment does not just select for , it also produces new variation. Nearly 3 decades ago, and in parallel with Odling-Smee's article ‘Niche-constructing phenotypes', West and King introduced the ‘ontogenetic niche’ to give the phenomena of exo genetic inheritance a formal name. Since then, a range of fields in the life sciences and medicine has amassed evidence that parents influence their offspring by means other than DNA (parental effects), and proposed mechanisms for how heritable variation can be environmentally induced and developmentally regulated. The concept of ‘developmental niche construction’ (DNC) elucidates how a diverse range of mechanisms contributes to the transgenerational transfer of developmental resources. My most central of claims is that whereas the selective niche of niche construction theory is primarily used to explain the active role of the organism in its selective environment, DNC is meant to indicate the active role of the organism in its developmental environment. The paper highlights the differences between the construction of the selective and the developmental niche, and explores the overall significance of DNC for evolutionary theory.

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