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.

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

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.

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.

Vertical alignment of liquid crystals using an in situ self-assembled molecular layer of saturated fatty acids

2017 ◽  
Vol 644 (1) ◽  
pp. 109-114
Author(s):  
Jae Hong Kim ◽  
Intae Son ◽  
Chunho Kim ◽  
Byungsun Lee ◽  
Ji Yong Yoo ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Liquid Crystals ◽  
Saturated Fatty Acids ◽  
Molecular Layer ◽  
Vertical Alignment ◽  
Self Assembled

scholarly journals Targeted Delivery of Nanoparticulate Cytochrome C into Glioma Cells Through the Proton-Coupled Folate Transporter

Biomolecules ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 154 ◽  
Author(s):  
Yuriy V. Kucheryavykh ◽  
Josue Davila ◽  
Jescelica Ortiz-Rivera ◽  
Mikhael Inyushin ◽  
Luis Almodovar ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Targeted Delivery ◽  
Folate Receptor ◽  
Glioma Cells ◽  
Confocal Imaging ◽  
Patch Clamp Recording ◽  
Whole Cell Patch Clamp ◽  
Cultured Astrocytes ◽  
Starting Point ◽  
Cyt C

In this study, we identified the proton-coupled folate transporter (PCFT) as a route for targeted delivery of drugs to some gliomas. Using the techniques of confocal imaging, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and small interfering (siRNA) knockdown against the PCFT, we demonstrated that Gl261 and A172 glioma cells, but not U87 and primary cultured astrocytes, express the PCFT, which provides selective internalization of folic acid (FA)-conjugated cytochrome c-containing nanoparticles (FA-Cyt c NPs), followed by cell death. The FA-Cyt c NPs (100 µg/mL), had no cytotoxic effects in astrocytes but caused death in glioma cells, according to their level of expression of PCFT. Whole-cell patch clamp recording revealed FA-induced membrane currents in FA-Cyt c NPs-sensitive gliomas, that were reduced by siRNA PCFT knockdown in a similar manner as by application of FA-Cyt c NPs, indicating that the PCFT is a route for internalization of FA-conjugated NPs in these glioma cells. Analysis of human glioblastoma specimens revealed that at least 25% of glioblastomas express elevated level of either PCFT or folate receptor (FOLR1). We conclude that the PCFT provides a mechanism for targeted delivery of drugs to some gliomas as a starting point for the development of efficient methods for treating gliomas with high expression of PCFT and/or FOLR1.

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.

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