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

2021 ◽  
Vol 17 (5) ◽  
pp. e1009486
Author(s):  
Zannatul Ferdous ◽  
Silke Fuchs ◽  
Volker Behrends ◽  
Nikolaos Trasanidis ◽  
Robert M. Waterhouse ◽  
...  
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

Vitellogenesis 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 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.

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 Double face of cytochrome c in cancers. New look into human breast ducts with Raman imaging

2021 ◽  
Author(s):  
Halina Abramczyk ◽  
Beata Brozek-Pluska ◽  
Monika Kopec
Keyword(s):  
Fatty Acids ◽  
Epithelial Cells ◽  
Cytochrome C ◽  
Saturated Fatty Acids ◽  
Cancer Development ◽  
Cancer Drug ◽  
Dual Function ◽  
Starting Point ◽  
Cyt C

Cytochrome c (Cyt c) is a key protein that is needed to maintain life (respiration) and cell death (apoptosis). The dual-function of Cyt c comes from its capability to act as mitochondrial redox carrier that transfers electrons between the membrane-embedded complexes III and IV and to serve as a cytoplasmic apoptosis-triggering agent, activating the caspase cascade.1–6 However, the precise roles of Cyt c in mitochondria, cytoplasm and extracellular matrix under normal and pathological conditions are not completely understood.7–9 To date, no pathway of Cyt c release that results in caspase activation has been compellingly demonstrated in any invertebrate.10 The significance of mitochondrial dysfunctionality has not been studied in ductal carcinoma to the best of our knowledge.1 Here we show that proper concentration of monounsaturated fatty acids, saturated fatty acids, cardiolipin and Cyt c is critical in the correct breast ductal functioning and constitutes an im-portant parameter to assess breast epithelial cells integrity and homeostasis. We look inside hu-man breast ducts answering fundamental questions about location and distribution of various biochemical components inside the lumen, epithelial cells of the duct and the extracellular ma-trix around the cancer duct during cancer development in situ. We found in histopathologically controlled breast cancer duct that Cyt c, cardiolipin, and palmitic acid are the main components inside the lumen of cancerous duct in situ. The presented results show direct evidence that Cyt c is released to the lumen from the epithelial cells in cancerous duct. In contrast the lumen in nor-mal duct is empty and free of Cyt c. Our results demonstrate how Cyt c is likely to function in cancer development. We anticipate our results to be a starting point for more sophisticated in vitro and in vivo animal models. For example, the correlation between concentration of Cyt c and cancer grade could be tested in various types of cancer. Furthermore, Cyt c is a target of anti-cancer drug development 11,12 and a well-defined and quantitative Raman based assay for oxidative phosphorylation and apoptosis will be relevant for such developments.

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.

Distinct Influence of Saturated Fatty Acids on Malignant and Nonmalignant Human Lung Epithelial Cells

Lipids ◽  
2020 ◽  
Vol 55 (2) ◽  
pp. 117-126
Author(s):  
Katarzyna Reczyńska ◽  
Dipesh Khanal ◽  
Kinga Pielichowska ◽  
Elżbieta Pamuła ◽  
Wojciech Chrzanowski
Keyword(s):  
Fatty Acids ◽  
Epithelial Cells ◽  
Human Lung ◽  
Saturated Fatty Acids ◽  
Lung Epithelial Cells ◽  
Lung Epithelial ◽  
Human Lung Epithelial Cells

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 Dietary omega-6, but not omega-3, polyunsaturated or saturated fatty acids increase inflammation in primary lung mesenchymal cells

2018 ◽  
Vol 314 (6) ◽  
pp. L922-L935 ◽  
Author(s):  
Sandra Rutting ◽  
Dia Xenaki ◽  
Edmund Lau ◽  
Jay Horvat ◽  
Lisa G. Wood ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Epithelial Cells ◽  
Airway Inflammation ◽  
Saturated Fatty Acids ◽  
Dietary Fatty Acids ◽  
Omega 3 ◽  
Obese Person ◽  
Tnf Α ◽  
Phosphoinositide 3 Kinase

Obesity is an important risk factor for developing severe asthma. Dietary fatty acids, which are increased in sera of obese individuals and after high-fat meals, activate the innate immune system and induce inflammation. This study investigated whether dietary fatty acids directly cause inflammation and/or synergize with obesity-induced cytokines in primary human pulmonary fibroblasts in vitro. Fibroblasts were challenged with BSA-conjugated fatty acids [ω-6 polyunsaturated fatty acids (PUFAs) and ω-3 PUFAs or saturated fatty acids (SFAs)], with or without TNF-α, and release of the proinflammatory cytokines, IL-6 and CXCL8, was measured. We found that the ω-6 PUFA arachidonic acid (AA), but not ω-3 PUFAs or SFAs, upregulates IL-6 and CXCL8 release. Combined AA and TNF-α challenge resulted in substantially greater cytokine release than either alone, demonstrating synergy. Synergistic upregulation of IL-6, but not CXCL8, was mainly mediated via cyclooxygenase (COX). Inhibition of p38 MAPK reduced CXCL8 release, induced by AA and TNF-α alone, but not in combination. Synergistic CXCL8 release, following AA and TNF-α challenge, was not medicated via a single signaling pathway (MEK1, JNK, phosphoinositide 3-kinase, and NF-κB) nor by hyperactivation of NF-κB or p38. To investigate if these findings occur in other airway cells, effects of AA in primary human airway smooth muscle (ASM) cells and human bronchial epithelial cells were also investigated. We found proinflammatory effects in ASM cells but not epithelial cells. This study suggests that diets rich in ω-6 PUFAs might promote airway inflammation via multiple pathways, including COX-dependent and -independent pathways, and in an obese person, may lead to more severe airway inflammation.

scholarly journals Neonatal Mouse Gut Metabolites Influence Cryptosporidium parvum Infection in Intestinal Epithelial Cells

mBio ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. e02582-20
Author(s):  
Kelli L. VanDussen ◽  
Lisa J. Funkhouser-Jones ◽  
Marianna E. Akey ◽  
Deborah A. Schaefer ◽  
Kevin Ackman ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Epithelial Cells ◽  
Cryptosporidium Parvum ◽  
Intestinal Epithelial Cells ◽  
Saturated Fatty Acids ◽  
Intestinal Lumen ◽  
Intestinal Epithelial ◽  
Content Type ◽  
Long Chain

ABSTRACTThe protozoan parasite Cryptosporidium sp. is a leading cause of diarrheal disease in those with compromised or underdeveloped immune systems, particularly infants and toddlers in resource-poor localities. As an enteric pathogen, Cryptosporidium sp. invades the apical surface of intestinal epithelial cells, where it resides in close proximity to metabolites in the intestinal lumen. However, the effect of gut metabolites on susceptibility to Cryptosporidium infection remains largely unstudied. Here, we first identified which gut metabolites are prevalent in neonatal mice when they are most susceptible to Cryptosporidium parvum infection and then tested the isolated effects of these metabolites on C. parvum invasion and growth in intestinal epithelial cells. Our findings demonstrate that medium or long-chain saturated fatty acids inhibit C. parvum growth, perhaps by negatively affecting the streamlined metabolism in C. parvum, which is unable to synthesize fatty acids. Conversely, long-chain unsaturated fatty acids enhanced C. parvum invasion, possibly by modulating membrane fluidity. Hence, gut metabolites, either from diet or produced by the microbiota, influence C. parvum growth in vitro and may also contribute to the early susceptibility to cryptosporidiosis seen in young animals.IMPORTANCECryptosporidium sp. occupies a unique intracellular niche that exposes the parasite to both host cell contents and the intestinal lumen, including metabolites from the diet and produced by the microbiota. Both dietary and microbial products change over the course of early development and could contribute to the changes seen in susceptibility to cryptosporidiosis in humans and mice. Consistent with this model, we show that the immature gut metabolome influenced the growth of Cryptosporidium parvumin vitro. Interestingly, metabolites that significantly altered parasite growth were fatty acids, a class of molecules that Cryptosporidium sp. is unable to synthesize de novo. The enhancing effects of polyunsaturated fatty acids and the inhibitory effects of saturated fatty acids presented in this study may provide a framework for future studies into this enteric parasite’s interactions with exogenous fatty acids during the initial stages of infection.

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