scholarly journals The Evolutionary Pattern and the Regulation of Stearoyl-CoA Desaturase Genes

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Xiaoyun Wu ◽  
Xiaoju Zou ◽  
Qing Chang ◽  
Yuru Zhang ◽  
Yunhai Li ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Relative Rate ◽  
Saturated Fatty Acids ◽  
Purifying Selection ◽  
Similar Rate ◽  
Ratio Test ◽  
Evolutionary Patterns ◽  
Variable Binding ◽  
Evolutionary Pattern ◽  
Stearoyl Coa Desaturase

Stearoyl-CoA desaturase (SCD) is a key enzyme that converts saturated fatty acids (SFAs) to monounsaturated fatty acids (MUFAs) in the biosynthesis of fat. To date, two isoforms ofscdgene (scd1andscd5) have been found widely existent in most of the vertebrate animals. However, the evolutionary patterns of both isofoms and the function ofscd5are poorly understandable. Herein, we aim to characterize the evolutionary pattern ofscdgenes and further predict the function differentiation ofscdgenes. The sequences ofscdgenes were highly conserved among eukaryote. Phylogenetic analysis identified two duplications ofscdgene early in vertebrate evolution. The relative rate ratio test, branch-specificdN/dSratio tests, and branch-sitedN/dSratio tests all suggested that thescdgenes were evolved at a similar rate. The evolution ofscdgenes among eukaryote was under strictly purifying selection though several sites inscd1andscd5were undergone a relaxed selection pressure. The variable binding sites by transcriptional factors at the 5′-UTR and by miRNAs at 3′-UTR ofscdgenes suggested that the regulators ofscd5may be different from that ofscd1. This study promotes our understanding of the evolutionary patterns and function of SCD genes in eukaryote.

scholarly journals Analysis of substitution rates showed that TLR5 is evolving at different rates among mammalian groups

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Ana Pinheiro ◽  
Ana Águeda-Pinto ◽  
José Melo-Ferreira ◽  
Fabiana Neves ◽  
Joana Abrantes ◽  
...  
Keyword(s):  
Substitution Rate ◽  
Relative Rate ◽  
Purifying Selection ◽  
Genetic Distances ◽  
Major Protein ◽  
Substitution Rates ◽  
Evolutionary Pattern ◽  
Branch Model ◽  
Rate Test ◽  
Species Specific

Abstract Background Toll-like receptors (TLRs) are the most widely studied innate immunity receptors responsible for recognition of invading pathogens. Among the TLR family, TLR5 is the only that senses and recognizes flagellin, the major protein of bacterial flagella. TLR5 has been reported to be under overall purifying selection in mammals, with a small proportion of codons under positive selection. However, the variation of substitution rates among major mammalian groups has been neglected. Here, we studied the evolution of TLR5 in mammals, comparing the substitution rates among groups. Results In this study we analysed the TLR5 substitution rates in Euungulata, Carnivora, Chiroptera, Primata, Rodentia and Lagomorpha, groups. For that, Tajima’s relative rate test, Bayesian inference of evolutionary rates and genetic distances were estimated with CODEML’s branch model and RELAX. The combined results showed that in the Lagomorpha, Rodentia, Carnivora and Chiroptera lineages TLR5 is evolving at a higher substitution rate. The RELAX analysis further suggested a significant relaxation of selective pressures for the Lagomorpha (K = 0.22, p < 0.01), Rodentia (K = 0.58, p < 0.01) and Chiroptera (K = 0.65, p < 0.01) lineages and for the Carnivora ancestral branches (K = 0.13, p < 0.01). Conclusions Our results show that the TLR5 substitution rate is not uniform among mammals. In fact, among the different mammal groups studied, the Lagomorpha, Rodentia, Carnivora and Chiroptera are evolving faster. This evolutionary pattern could be explained by 1) the acquisition of new functions of TLR5 in the groups with higher substitution rate, i.e. TLR5 neofunctionalization, 2) by the beginning of a TLR5 pseudogenization in these groups due to some redundancy between the TLRs genes, or 3) an arms race between TLR5 and species-specific parasites.

Stearoyl CoA Desaturase 1 (SCD1) Is Upregulated in Rapidly Growing Myeloma Cells and Is Required for Cell Proliferation,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3943-3943 ◽  
Author(s):  
Sathisha Upparahalli Venkateshaiah ◽  
Sharmin Khan ◽  
Wen Ling ◽  
Linda Saint John ◽  
Rakesh Bam ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Cell Proliferation ◽  
High Risk ◽  
Rapid Growth ◽  
Conflicts Of Interest ◽  
Saturated Fatty Acids ◽  
Molecular Signature ◽  
Myeloma Cells ◽  
Stearoyl Coa Desaturase

Abstract Abstract 3943 Myeloma plasma cell high labeling index and molecular signature of proliferation are strong adverse prognostic factors often characterize patients with high risk disease. The overall aim of the study was to identify cell proliferation associated genes implicating highly proliferating myeloma cells in the supportive bone marrow environment. To shed light on molecular factors associated with rapid growth of myeloma cells, primary myeloma cells from 10 patients, molecularly classified as high risk were engrafted in SCID-rab mice. Growth rate of myeloma varied between patients' cells but in all cases myeloma propagated within and surrounding the supportive implanted bone but not in any murine organs. We performed global gene expression profiling (GEP) on myeloma plasma cells recovered from mice and compared their GEP with the baseline, pre-injected myeloma cells. Based on stringent criteria (e.g. p<0.05, >2 folds) approximately 127 probe sets were commonly overexpressed and 36 probe sets underexpressed in myeloma cells from SCID-rab mice than baseline myeloma cells. Genes whose expression altered were mainly associated with proliferation, survival, metabolism, transcription and immunity. Among genes involved in cell proliferation we indentified stearoyl CoA desaturase 1 (SCD1), which was upregulated in 7 of 10 cases by overall 2.3±0.6 folds (p<0.01). In coculture of primary myeloma cells with the supportive osteoclasts (n=8), SCD1 was upregulated in 6 of 8 cocultures by 5.6±2.4 folds (p<0.02). SCD1 upregulation in vivo and in cocultures was consistently observed in 3 different GEP probe sets. SCD1 is a rate-limiting enzyme responsible for synthesis of monounsaturated fatty acids and is activated in highly proliferating tumor cells to sustain the increasing demand of new membrane phospholipids and energy storage, and reducing intracellular content of cytotoxic saturated fatty acids. Various SCD1 inhibitors are currently being evaluated for metabolic diseases. In vitro, small molecule SCD1 inhibitor (BioVision) dose dependently (0.1–10 μM, 96 hrs) inhibited growth of rapidly growing myeloma cell lines (n=5) but had moderate inhibitory effect on their survival. Compared to control vehicle-treated cultures, numbers of viable myeloma cells were reduced by 76±5% (p<0.008) and 51±3% (p<0.0001) following treatment with 0.1 μM and 5 μM of SCD1 inhibitor, respectively. Cell viability was reduced from 91±0.5% in control groups to 82±3% (p<0.05) and 73±5% (p<0.03) in cultures treated with 0.1 μM and 5 μM of SCD1 inhibitor, respectively. In vivo, luciferase-expressing H929 myeloma cells were engrafted in SCID-rab mice. Myeloma growth was monitored by live-animal bioluminescence imaging. Upon establishment of myeloma hosts were treated with SCD1 inhibitor using Alzet osmotic pump directly connected to the open side of the implanted bone and constantly released drug (1.25 μg/hour) or vehicle over a period of 2 weeks. At experiment's end myeloma burden was increased from pretreatment levels by 49±3 folds and 30±3 folds in control vehicle- and SCD1 inhibitor-treated hosts, respectively (p<0.01). We conclude that SCD1 is highly activated in proliferating myeloma cells and is essential for their rapid growth. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Stearoyl-CoA Desaturase 1 as a Therapeutic Target for the Treatment of Cancer

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 948 ◽  
Author(s):  
Zuzanna Tracz-Gaszewska ◽  
Pawel Dobrzyn
Keyword(s):  
Fatty Acids ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Current Knowledge ◽  
Saturated Fatty Acids ◽  
Monounsaturated Fatty Acids ◽  
Cancer Aggressiveness ◽  
Wide Range ◽  
Stearoyl Coa Desaturase ◽  
Poor Outcomes

A distinctive feature of cancer cells of various origins involves alterations of the composition of lipids, with significant enrichment in monounsaturated fatty acids. These molecules, in addition to being structural components of newly formed cell membranes of intensely proliferating cancer cells, support tumorigenic signaling. An increase in the expression of stearoyl-CoA desaturase 1 (SCD1), the enzyme that converts saturated fatty acids to ∆9-monounsaturated fatty acids, has been observed in a wide range of cancer cells, and this increase is correlated with cancer aggressiveness and poor outcomes for patients. Studies have demonstrated the involvement of SCD1 in the promotion of cancer cell proliferation, migration, metastasis, and tumor growth. Many studies have reported a role for this lipogenic factor in maintaining the characteristics of cancer stem cells (i.e., the population of cells that contributes to cancer progression and resistance to chemotherapy). Importantly, both the products of SCD1 activity and its direct impact on tumorigenic pathways have been demonstrated. Based on these findings, SCD1 appears to be a significant player in the development of malignant disease and may be a promising target for anticancer therapy. Numerous chemical compounds that exert inhibitory effects on SCD1 have been developed and preclinically tested. The present review summarizes our current knowledge of the ways in which SCD1 contributes to the progression of cancer and discusses opportunities and challenges of using SCD1 inhibitors for the treatment of cancer.

Role of stearoyl-CoA desaturase-1 in skeletal muscle function and metabolism

2013 ◽  
Vol 305 (7) ◽  
pp. E767-E775 ◽  
Author(s):  
Alexis D. Stamatikos ◽  
Chad M. Paton
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Lipid Metabolism ◽  
Saturated Fatty Acids ◽  
Monounsaturated Fatty Acids ◽  
Skeletal Muscle Function ◽  
Skeletal Muscle Lipid ◽  
Stearoyl Coa Desaturase ◽  
Scd1 Expression

Stearoyl-CoA desaturase-1 (SCD1) converts saturated fatty acids (SFA) into monounsaturated fatty acids and is necessary for proper liver, adipose tissue, and skeletal muscle lipid metabolism. While there is a wealth of information regarding SCD1 expression in the liver, research on its effect in skeletal muscle is scarce. Furthermore, the majority of information about its role is derived from global knockout mice, which are known to be hypermetabolic and fail to accumulate SCD1's substrate, SFA. We now know that SCD1 expression is important in regulating lipid bilayer fluidity, increasing triglyceride formation, and enabling lipogenesis and may protect against SFA-induced lipotoxicity. Exercise has been shown to increase SCD1 expression, which may contribute to an increase in intramyocellular triglyceride at the expense of free fatty acids and diacylglycerol. This review is intended to define the role of SCD1 in skeletal muscle and discuss the potential benefits of its activity in the context of lipid metabolism, insulin sensitivity, exercise training, and obesity.

scholarly journals Anopheles coluzzii stearoyl-CoA desaturase is essential for adult female survival and reproduction upon blood feeding

2020 ◽  
Author(s):  
Zannatul Ferdous ◽  
Silke Fuchs ◽  
Volker Behrends ◽  
Nikolaos Trasanidis ◽  
Dina Vlachou ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Epithelial Cells ◽  
Sterculic Acid ◽  
Transcriptional Profiling ◽  
Saturated Fatty Acids ◽  
Blood Feeding ◽  
Phenotypic Characterization ◽  
Anopheles Coluzzii ◽  
Survival And Reproduction ◽  
Stearoyl Coa Desaturase

AbstractVitellogenesis and oocyte maturation require anautogenous female Anopheles mosquitoes to obtain a bloodmeal from a vertebrate host. The bloodmeal is rich in proteins that are readily broken down into amino acids in the midgut lumen and absorbed by the midgut epithelial cells where they are converted into lipids and then transported to other tissues including ovaries. The stearoyl-CoA desaturase (SCD) plays a pivotal role in this process by converting saturated (SFAs) to unsaturated (UFAs) fatty acids; the latter being essential for maintaining cell membrane fluidity amongst other housekeeping functions. Here, we report the functional and phenotypic characterization of SCD1 in the malaria vector mosquito Anopheles coluzzii. We show that RNA interference (RNAi) silencing of SCD1 and administration of sterculic acid (SA), a small molecule inhibitor of SCD1, significantly impact on the survival and reproduction of female mosquitoes following blood feeding. Microscopic observations reveal that the mosquito thorax is quickly filled with blood, a phenomenon likely caused by the collapse of midgut epithelial cell membranes, and that epithelial cells are depleted of lipid droplets and oocytes fail to mature. Transcriptional profiling shows that genes involved in protein, lipid and carbohydrate metabolism and immunity-related genes are the most affected by SCD1 knock down (KD) in blood-fed mosquitoes. Metabolic profiling reveals that these mosquitoes exhibit increased amounts of saturated fatty acids and TCA cycle intermediates, highlighting the biochemical framework by which the SCD1 KD phenotype manifests as a result of a detrimental metabolic syndrome. Accumulation of SFAs is also the likely cause of the potent immune response observed in the absence of infection, which resembles an auto-inflammatory condition. These data provide insights into mosquito bloodmeal metabolism and lipid homeostasis and could inform efforts to develop novel interventions against mosquito-borne diseases.

scholarly journals Sequential dynamics of Stearoyl-CoA Desaturase-1(SCD1) /ligand binding and unbinding mechanism: A computational study

2020 ◽  
Author(s):  
Anna B. Petroff ◽  
Rebecca L. Weir ◽  
Charles R. Yates ◽  
Joseph D. Ng ◽  
Jerome Baudry
Keyword(s):  
Molecular Dynamics ◽  
Fatty Acids ◽  
Computational Study ◽  
Saturated Fatty Acids ◽  
Monounsaturated Fatty Acids ◽  
Membrane Composition ◽  
Endoplasmic Reticulum Protein ◽  
Metabolic Protein ◽  
Stearoyl Coa Desaturase ◽  
Dynamic Series

AbstractStearoyl-CoA desaturase-1 (SCD1 or delta-9 desaturase, D9D) is a key metabolic protein that modulates cellular inflammation and stress, but overactivity of SCD1 is associated with diseases including cancer and metabolic syndrome. This transmembrane endoplasmic reticulum protein converts saturated fatty acids into monounsaturated fatty acids, primarily stearoyl-CoA into oleoyl-CoA, which are critical products for energy metabolism and membrane composition. The present computational molecular dynamics study characterizes the molecular dynamics of SCD1 with substrate, product, and as apoprotein. The modeling of SCD1:fatty acid interactions suggests that 1) SCD1:CoA moiety interactions open the substrate binding tunnel, 2) SCD1 stabilizes a substrate conformation favorable for desaturation, and 3) SCD1:product interactions result in an opening of the tunnel, possibly allowing product exit into the surrounding membrane. Together, these results describe a highly dynamic series of SCD1 conformations resulting from the enzyme:cofactor:substrate interplay that inform drug-discovery efforts.

Induction of stearoyl-CoA desaturase protects human arterial endothelial cells against lipotoxicity

2008 ◽  
Vol 295 (2) ◽  
pp. E339-E349 ◽  
Author(s):  
Andreas Peter ◽  
Cora Weigert ◽  
Harald Staiger ◽  
Kilian Rittig ◽  
Alexander Cegan ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Fatty Acids ◽  
Endothelial Cells ◽  
Inflammatory Cytokines ◽  
Cell Apoptosis ◽  
Saturated Fatty Acids ◽  
Monounsaturated Fatty Acids ◽  
Hek 293 ◽  
Stearoyl Coa Desaturase ◽  
Arterial Endothelial Cells

Endothelial lipotoxicity has been implicated in the pathogenesis of multiple stages of cardiovascular disease from early endothelial dysfunction to manifest atherosclerosis and its complications. Saturated free fatty acids are the major inducers of endothelial cell apoptosis and inflammatory cytokines. In humans, the enzyme human stearoyl-CoA desaturase-1 (hSCD-1) is the limiting step of the desaturation of saturated to monounsaturated fatty acids. Since we could demonstrate the expression of SCD-1 in primary human arterial endothelial cells (HAECs), we aimed to prove a beneficial role of upregulated hSCD-1 expression. In contrast to other cells that are less susceptible to lipotoxicity, hSCD-1 was not upregulated in HAECs upon palmitate treatment. Following that, we could show that upregulation of hSCD-1 using the LXR activator TO-901317 in HAECs protects the cells against palmitate-induced lipotoxicity, cell apoptosis, and expression of inflammatory cytokines IL-6 and IL-8. Increased hSCD-1 activity was determined as increased C16:1/16:0 ratio and enhanced triglyceride storage in palmitate treated cells. The beneficial effect was clearly attributed to enhanced hSCD-1 activity. Overexpression of hSCD-1 blocked palmitate-induced cytotoxicity, and knockdown of hSCD-1 using siRNA abolished the protective effect of TO-901317 in HEK-293 cells. Additionally, inhibition of hSCD-1 with 10/12 CLA blocked the effect of TO-901317 on palmitate-induced lipotoxicity, cell apoptosis, and inflammatory cytokine induction in HAECs. We conclude that upregulation of hSCD-1 leads to a desaturation of saturated fatty acids and facilitates their esterification and storage, thereby preventing downstream effects of lipotoxicity in HAECs. These findings add a novel aspect to the atheroprotective actions of LXR activators in cardiovascular disease.

scholarly journals Influence of Feeding Linseed on SCD Activity in Grazing Goat Mammary Glands

Animals ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 786 ◽  
Author(s):  
Raffaella Tudisco ◽  
Biagina Chiofalo ◽  
Vittorio Lo Presti ◽  
Valeria Maria Morittu ◽  
Giuseppe Moniello ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Treatment Group ◽  
Milk Fat ◽  
Saturated Fatty Acids ◽  
Mammary Glands ◽  
Control Group ◽  
Dairy Goats ◽  
Milk Fatty Acids ◽  
Homogeneous Groups ◽  
Stearoyl Coa Desaturase

The effects of linseed feeding on the stearoyl-CoA desaturase (SCD) activity were evaluated on grazing dairy goats divided into two homogeneous groups (C, control, and L, treated) fed the same amount of concentrate which, for group L was supplemented with linseed. Milk yield was unaffected by the treatment. Group L showed significantly higher milk fat (4.10% vs 2.94%, p < 0.01) than group S. Within milk fatty acids, group C showed significantly higher levels of saturated fatty acids and lower values of mono-unsaturated and polyunsaturated fatty acids. In group L, total CLAs were higher than in group S (0.646% vs 0.311%; p < 0.01) mainly because of the differences in CLA cis9 trans 11 (0.623% vs 0.304%; p < 0.01). In treated animals, SCD activity, measured as cis9 C14:1/C14:0, was lower than in the control group, mainly in July and August.

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