Chemistry and Physics of Lipids最新文献

{"title":"Monitoring galactolipid digestion and simultaneous changes in lipid-bile salt micellar organization by real-time NMR spectroscopy","authors":"Moulay Sahaka ,&nbsp;Olivier Bornet ,&nbsp;Achille Marchand ,&nbsp;Dominique Lafont ,&nbsp;Brigitte Gontero ,&nbsp;Frédéric Carrière ,&nbsp;Hélène Launay","doi":"10.1016/j.chemphyslip.2023.105361","DOIUrl":"10.1016/j.chemphyslip.2023.105361","url":null,"abstract":"<div><p>The use of Nuclear Magnetic Resonance spectroscopy for studying lipid digestion in vitro most often consists of quantifying lipolysis products after they have been extracted from the reaction medium using organic solvents. However, the current sensitivity level of NMR spectrometers makes possible to avoid the extraction step and continuously quantify the lipids directly in the reaction medium. We used real-time ¹H NMR spectroscopy and guinea pig pancreatic lipase-related protein 2 (GPLRP2) as biocatalyst to monitor in situ the lipolysis of monogalactosyl diacylglycerol (MGDG) in the form of mixed micelles with the bile salt sodium taurodeoxycholate (NaTDC). Residual substrate and lipolysis products (monogalactosyl monoacylglycerol (MGMG); monogalactosylglycerol (MGG) and octanoic acid (OA) were simultaneously quantified throughout the reaction thanks to specific proton resonances. Lipolysis was complete with the release of all MGDG fatty acids. These results were confirmed by thin layer chromatography (TLC) and densitometry after lipid extraction at different reaction times. Using diffusion-ordered NMR spectroscopy (DOSY), we could also estimate the diffusion coefficients of all the reaction compounds and deduce the hydrodynamic radius of the lipid aggregates in which they were present. It was shown that MGDG-NaTDC mixed micelles with an initial hydrodynamic radius r_H of 7.3 ± 0.5 nm were changed into smaller micelles of NaTDC-MGDG-MGMG of 2.3 ± 0.5 nm in the course of the lipolysis reaction, and finally into NaTDC-OA mixed micelles (r_H of 2.9 ± 0.5 nm) and water soluble MGG. These results provide a better understanding of the digestion of galactolipids by PLRP2, a process that leads to the complete micellar solubilisation of their fatty acids and renders their intestinal absorption possible.</p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"258 ","pages":"Article 105361"},"PeriodicalIF":3.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S000930842300083X/pdfft?md5=7949f0a6afc8b93348193638444baadc&pid=1-s2.0-S000930842300083X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138045681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating the functional role of human ABHD16B lipase in regulating triacylglycerol mobilization and membrane lipid synthesis in Saccharomyces cerevisiae","authors":"Raja Narayanasamy ,&nbsp;Dandamudi Usharani ,&nbsp;Ram Rajasekharan","doi":"10.1016/j.chemphyslip.2023.105353","DOIUrl":"10.1016/j.chemphyslip.2023.105353","url":null,"abstract":"<div><p>Lipids are essential biological macromolecules that play a pivotal role in various physiological processes and cellular homeostasis. ABHD16B, a member of the α/β-hydrolase domain (ABHD) superfamily protein, has emerged as a potential key regulator in lipid metabolism. However, the precise role of human ABHD16B in lipid metabolism remains unclear. In this study, we reported the overexpression of ABHD16B in <em>Saccharomyces cerevisiae</em> to determine its physiological relevance in lipid metabolism. Through <em>in vivo</em> [¹⁴C]acetate labeling experiments, we observed that overexpression of ABHD16B causes a decrease in cellular triacylglycerol (TAG) levels and a concurrent increase in phospholipid synthesis in wild-type cells. Mass spectrometry (LC–MS/MS) analysis further corroborated these findings, showing a significant decrease in TAGs with a carbon chain length of 48 and an increase in major phospholipid species, specifically 34:2, upon overexpression of ABHD16B. Confocal microscopy analysis revealed a reduction in the number of lipid droplets in strains overexpressing ABHD16B, consistent with the observed decrease in neutral lipids. Additionally, qRT-PCR analysis indicated a high phospholipid synthetic activity of ABHD16B and a potential decrease in TAG levels in wild-type yeast, possibly due to upregulation of endogenous TAG hydrolytic enzymes, as confirmed using <em>3tgls</em>Δ mutant strain. Furthermore, GC-MS analysis revealed significant modifications in fatty acid composition upon ABHD16B overexpression. Collectively, our results underscore the influence of ABHD16B overexpression on TAG levels, phospholipid synthesis, lipid droplet dynamics, and fatty acid composition. These findings reveal a complex interplay between TAG hydrolysis and phospholipid synthesis, highlighting the critical involvement of ABHD16B in lipid homeostasis and providing further insights into its regulatory function in cellular lipid metabolism.</p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"258 ","pages":"Article 105353"},"PeriodicalIF":3.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0009308423000750/pdfft?md5=88c09caa313909654509f6e549ded1c5&pid=1-s2.0-S0009308423000750-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72012831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unsaturation of serine lipids modulating the interaction of a cytosporone with models of the external leaflet of tumorigenic cell membranes","authors":"Guilherme Nuñez Jaroque,&nbsp;Augusto Leonardo dos Santos,&nbsp;Patrícia Sartorelli,&nbsp;Luciano Caseli","doi":"10.1016/j.chemphyslip.2023.105363","DOIUrl":"10.1016/j.chemphyslip.2023.105363","url":null,"abstract":"<div><p>Cytosporone-B was isolated from fungi and incorporated in models of tumorigenic cell membranes using palmitoyloleoylglycerophosphoserine (POPS) and dipalmitoyl glycerophosphoserine (DPPS) lipids. While for DPPS, the compound condensed the monolayer and decreased the surface compressional modulus, it expanded and kept the compressional modulus for POPS. Hysteresis for compression-expansion cycles was more sensitive for POPS than for DPPS, while a high degree of destabilization was observed for POPS. As observed with infrared spectroscopy and Brewster angle microscopy, specific changes were selective regarding molecular organization and morphology. Atomic force microscopy for transferred monolayers as Langmuir-Blodgett films also confirmed such specificities. We believe these data can help understand the mechanism of action of bioactive drugs in lipid interfaces at the molecular level.</p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"258 ","pages":"Article 105363"},"PeriodicalIF":3.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0009308423000853/pdfft?md5=f997a61328a6651b49243b8ca79b906d&pid=1-s2.0-S0009308423000853-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138476416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel bioactive lipids enhanced HDL-mediated cholesterol efflux from macrophages through the ABCA1 receptor pathway","authors":"Ali Khattib ,&nbsp;Manar Shmet ,&nbsp;Rasha Ashkar ,&nbsp;Tony Hayek ,&nbsp;Soliman Khatib","doi":"10.1016/j.chemphyslip.2023.105367","DOIUrl":"10.1016/j.chemphyslip.2023.105367","url":null,"abstract":"<div><p>High-density lipoprotein (HDL) has traditionally been acknowledged as \"good cholesterol\" owing to its significant association with a decreased risk of atherosclerosis. This association is primarily attributed to HDL's direct involvement in cholesterol efflux capacity, which plays a pivotal role in reverse cholesterol transport. A novel active compound from <em>Nannochloropsis</em> microalgae termed lyso-DGTS, a lipid that contains EPA fatty acids, was previously isolated and found to increase paraoxonase 1 activity and enhance HDL-mediated cholesterol efflux and HDL-induced endothelial nitric oxide release. Here, the effect of different lyso-DGTS derivatives and analogs on HDL-mediated cholesterol efflux from macrophages was examined, and the mechanism was explored. Structure–activity relationships were established to characterize the essential lipid moieties responsible for HDL-mediated cholesterol efflux from macrophages. Lyso-DGTS, 1-carboxy-N-N-N-trimethyl-3-oleamidopropan-1-aminium, and lyso-platelet-activating factor increased HDL-mediated cholesterol efflux from macrophages dose-dependently, mainly via the ABCA1-mediated cholesterol efflux pathway. The effect of lyso-DGTS derivatives and analogs on the surface polarity of HDL was examined using the Laurdan generalized polarization (GP) assay. A reverse Pearson linear regression was obtained between Laurdan GP values and HDL-mediated cholesterol efflux. Because the incorporation of bioactive lipids into the surface phospholipid layer of HDL leads to a decrease in Laurdan GP, these bioactive lipids may induce lower phospholipid ordering and greater free space on the HDL particle surface, thereby enhancing apolipoprotein A1 binding to the ABCA1 receptor and improving ABCA1 cholesterol-mediated efflux. Our findings suggest a beneficial effect of lyso-DGTS and its bioactive lipid derivatives on increasing HDL-mediated cholesterol efflux activity from macrophages, which may impact atherosclerosis attenuation.</p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"258 ","pages":"Article 105367"},"PeriodicalIF":3.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0009308423000890/pdfft?md5=7ea020d7c9ebc26c842f5b41912c42ee&pid=1-s2.0-S0009308423000890-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138687540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A tribute to our friend and colleague Professor Richard M. Epand","authors":"Jose C. Bozelli Jr.,&nbsp;Raquel F. Epand,&nbsp;John Katsaras,&nbsp;Jesús Pérez-Gil","doi":"10.1016/j.chemphyslip.2023.105352","DOIUrl":"https://doi.org/10.1016/j.chemphyslip.2023.105352","url":null,"abstract":"","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"257 ","pages":"Article 105352"},"PeriodicalIF":3.4,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91962724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Raman imaging and chemometric methods in human normal bronchial and cancer lung cells: Raman biomarkers of lipid reprogramming","authors":"Monika Kopec,&nbsp;Karolina Beton-Mysur,&nbsp;Halina Abramczyk","doi":"10.1016/j.chemphyslip.2023.105339","DOIUrl":"https://doi.org/10.1016/j.chemphyslip.2023.105339","url":null,"abstract":"<div><p>This paper presents an approach to study biochemical changes in human normal bronchial cells (BEpiC) and human cancer lung cells (A549) by Raman spectroscopy and Raman imaging combined with chemometric methods. Based on Raman spectra and Raman imaging combined with chemometric methods we have proved that peaks at 845 cm⁻¹, 2845 cm⁻¹, 2936 cm⁻¹, 1444 cm⁻¹, 750 cm⁻¹, 1126 cm⁻¹, 1584 cm⁻¹, can be treated as Raman biomarkers probing phosphorylation, lipid reprogramming, oxidative phosphorylation and changes in cholesterol and cytochrome in normal and cancer cells. Raman analysis of the bands at 845 cm⁻¹, 2845 cm⁻¹, 1444 cm⁻¹, and 1126 cm⁻¹ in human cancer lung cells and human normal bronchial cells demonstrate enhanced phosphorylation and triglycerides <em>de novo</em> synthesis, reduced levels of cholesterol and cytochrome <em>c</em> in cancer cells. The sensitivity is equal to 100% (nucleus), 87.5% (mitochondria), 100% (endoplasmic reticulum), 87.5% (lipid droplets), 87.5% (cytoplasm), 87.5% (cell membrane) for A549 cell line and 83.3% (nucleus), 100% (mitochondria), 83.3% (endoplasmic reticulum), 100% (lipid droplets), 100% (cytoplasm), 83.3% (cell membrane) for BEpiC. The values of specificity for cross-validation equal 93.4% (nucleus), 85.5% (mitochondria), 89.5% (endoplasmic reticulum), 90.8% (lipid droplets), 61.8% (cytoplasm), 94.7% (cell membrane) for A549 cell line and 88.5% (nucleus), 85.9% (mitochondria), 85.9% (endoplasmic reticulum), 97.4% (lipid droplets), 75.6% (cytoplasm), 92.3% (cell membrane) for BEpiC. We have confirmed that Raman spectroscopy methods combined with PLS-DA are useful tools to monitor changes in human cancer lung cells and human normal bronchial cells.</p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"257 ","pages":"Article 105339"},"PeriodicalIF":3.4,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41080907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipidomic analysis identified potential predictive biomarkers of statin response in subjects with Familial hypercholesterolemia","authors":"Alvaro Cerda ,&nbsp;Raul Hernandes Bortolin ,&nbsp;Marcos Yukio Yoshinaga ,&nbsp;Renata Caroline Costa de Freitas ,&nbsp;Carolina Dagli-Hernandez ,&nbsp;Jessica Bassani Borges ,&nbsp;Victor Fernandes de Oliveira ,&nbsp;Rodrigo Marques Gonçalves ,&nbsp;Andre Arpad Faludi ,&nbsp;Gisele Medeiros Bastos ,&nbsp;Rosario Dominguez Crespo Hirata ,&nbsp;Mario Hiroyuki Hirata","doi":"10.1016/j.chemphyslip.2023.105348","DOIUrl":"10.1016/j.chemphyslip.2023.105348","url":null,"abstract":"<div><p><span><span>Familial hypercholesterolemia (FH) is a disorder of lipid metabolism that causes elevated low-density lipoprotein cholesterol (LDL-c) and increased premature atherosclerosis risk. </span>Statins<span><span><span> inhibit endogenous cholesterol biosynthesis, which reduces LDL-c plasma levels and prevent from cardiovascular events. This study aimed to explore the effects of statin treatment on serum </span>lipidomic<span> profile and to identify biomarkers of response in subjects with FH. Seventeen adult FH patients underwent a 6-week washout followed by 4-week treatment with atorvastatin (80 mg/day) or </span></span>rosuvastatin<span><span><span> (40 mg/day). LDL-c response was considered good (40–70 % reduction, n = 9) or poor (3–33 % reduction, n = 8). Serum lipidomic profile was analyzed by ultra-high-performance liquid chromatography combined with electrospray ionization tandem time-of-flight mass spectrometry, and data were analyzed using MetaboAnalyst v5.0. Lipidomic analysis identified 353 </span>lipids grouped into 16 classes. Statin treatment reduced drastically 8 of 13 lipid classes, generating a characteristic lipidomic profile with a significant contribution of </span>phosphatidylinositols (PI) 16:0/18:2, 18:0/18:1 and 18:0/18:2; and </span></span></span>triacylglycerols<span> (TAG) 18:2x2/18:3, 18:1/18:2/18:3, 16:1/18:2x2, 16:1/18:2/18:3 and 16:1/18:2/Arachidonic acid (p-adjusted &lt;0.05). Biomarker analysis implemented in MetaboAnalyst subsequently identified PI 16:1/18:0, 16:0/18:2 and 18:0/18:2 as predictors of statin response with and receiver operating characteristic (ROC) areas under the curve<span> of 0.98, 0.94 and 0.91, respectively. In conclusion, statins extensively modulate the overall serum lipid<span> composition of FH individuals and these findings suggest that phosphatidyl-inositol molecules are potential predictive biomarkers of statin response.</span></span></span></p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"257 ","pages":"Article 105348"},"PeriodicalIF":3.4,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41186896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The small-molecule kinase inhibitor ceritinib, unlike imatinib, causes a significant disturbance of lipid membrane integrity: A combined experimental and MD study","authors":"Markus Fischer ,&nbsp;Meike Luck ,&nbsp;Max Werle ,&nbsp;Alexander Vogel ,&nbsp;Mohammad Bashawat ,&nbsp;Kai Ludwig ,&nbsp;Holger A. Scheidt ,&nbsp;Peter Müller","doi":"10.1016/j.chemphyslip.2023.105351","DOIUrl":"10.1016/j.chemphyslip.2023.105351","url":null,"abstract":"<div><p><span>Ceritinib<span><span><span> and imatinib are small-molecule </span>protein kinase inhibitors<span> which are applied as therapeutic agents against various diseases. The fundamentals of their clinical use, i.e. their pharmacokinetics as well as the mechanisms of the inhibition of the respective kinases, are relatively well studied. However, the interaction of the drugs with membranes, which can be a possible cause of side effects, has hardly been investigated so far. Therefore, we have characterized the interaction of both drugs with </span></span>lipid membranes consisting of 1-palmitoyl-2-oleoyl-</span></span><em>sn</em><span><span>-glycero-3-phosphocholine (POPC) in the absence and in the presence of cholesterol. For determining the membrane impact of both drugs on a molecular level, different experimental (NMR, ESR, fluorescence) and theoretical (MD simulations) approaches were applied. The data show that ceritinib, in contrast to imatinib, interacts more effectively with membranes significantly affecting various physico-chemical membrane parameters like membrane order and transmembrane permeation of polar solutes. The pronounced membrane impact of ceritinib can be explained by a strong affinity of the drug towards POPC which competes with the POPC-cholesterol interaction by that attenuating the ordering effect of cholesterol. The data are relevant for understanding putative toxic and cytotoxic side effects of these drugs such as the triggering of </span>cell lysis or apoptosis.</span></p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"257 ","pages":"Article 105351"},"PeriodicalIF":3.4,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49672249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Saturation of fatty acids in phosphatidic acid uniquely alters transthyretin stability changing morphology and toxicity of amyloid fibrils","authors":"Abid Ali ,&nbsp;Kiryl Zhaliazka ,&nbsp;Tianyi Dou ,&nbsp;Aidan P. Holman ,&nbsp;Dmitry Kurouski","doi":"10.1016/j.chemphyslip.2023.105350","DOIUrl":"10.1016/j.chemphyslip.2023.105350","url":null,"abstract":"<div><p><span>Transthyretin (TTR) is a small, β-sheet-rich </span>tetrameric protein<span><span> that transports thyroid hormone thyroxine<span> and retinol. </span></span>Phospholipids<span>, including phosphatidic acid<span><span> (PA), can uniquely alter the stability of amyloidogenic proteins. However, the role of PA in TTR aggregation remains unclear. In this study, we investigated the effect of saturation of fatty acids (FAs) in PA on the rate of TTR aggregation. We also reveal the extent to which PAs with different length and saturation of FAs altered the morphology and secondary structure of TTR aggregates. Our results showed that TTR aggregation in the equimolar presence of PAs with different length and saturation of FAs yielded structurally and morphologically different fibrils compared to those formed in the lipid-free environment. We also found that PAs drastically lowered the toxicity of TTR aggregates formed in the presence of this phospholipid. These results shed light on the role of PA in the stability of TTR and transthyretin </span>amyloidosis.</span></span></span></p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"257 ","pages":"Article 105350"},"PeriodicalIF":3.4,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49672250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Organic synthesis of 1,2-dipalmitoyl-rac-glycero-3-phosphatidylethanolamine and its effect on the induction of apoptosis in normal human lung fibroblasts","authors":"Beatriz Tlatelpa-Romero ,&nbsp;David Atahualpa Contreras-Cruz ,&nbsp;Gabriel Guerrero-Luna ,&nbsp;María Guadalupe Hernández-Linares ,&nbsp;Sinuhé Ruiz-Salgado ,&nbsp;Criselda Mendoza-Milla ,&nbsp;Yair Romero ,&nbsp;René de-la-Rosa Paredes ,&nbsp;Luis F. Oyarzábal ,&nbsp;Diego Alejandro Mendoza-Sámano ,&nbsp;Jiovani Alfredo Galván-León ,&nbsp;Luis G. Vázquez-de-Lara","doi":"10.1016/j.chemphyslip.2023.105349","DOIUrl":"10.1016/j.chemphyslip.2023.105349","url":null,"abstract":"<div><h3>Background /objective</h3><p>The phospholipid 1,2-dipalmitoyl-<em>rac</em>-glycero-3-phosphatidylethanolamine (PE) comprises two fatty acid chains: glycerol, phosphate, and ethanolamine. PE participates in critical cellular processes such as apoptosis and autophagy, which places it as a target for designing new therapeutic alternatives in diseases such as pulmonary fibrosis. Therefore, this study aimed obtain PE through a six-step organic synthesis pathway and determine its biological effect on apoptosis induction in normal human lung fibroblasts (NHLF).</p></div><div><h3>Methodology</h3><p>The first step of the organic synthesis route began with protected glycerol that was benzylated at <em>sn</em>-3; later, it was deprotected to react with palmitic acid at <em>sn</em>-1, <em>sn</em>-2. To remove the benzyl group, hydrogenation was performed with palladium on carbon (Pd/C); subsequently, the molecule was phosphorylated in <em>sn</em>-3 with phosphorus oxychloride and triethylamine, and the intermediate was hydrolyzed in an acid medium to obtain the final compound. After PE synthesis, apoptosis assessment was performed: apoptosis was induced using exposure to annexin V-FITC/propidium iodide-ECD (PI) and quantified using flow cytometry. The experiments were performed in three NHLF cell lines with different concentrations of PE 10, 100 and 1000 µg/mL for 24 and 48 h.</p></div><div><h3>Results</h3><p>The PE obtained by organic synthesis presented a melting point of 190–192 °C, a purity of 95%, and a global yield of 8%. The evaluation of apoptosis with flow cytometry showed that at 24 h, exposure to PE 10, 100, and 1000 µg/mL induces early apoptosis in 19.42%− 25.54%, while late apoptosis was only significant <em>P &lt;</em> 0.05 in cells challenged with 100 µg/mL PE. At 48 h, NHLF exposed to PE 10, 100, and 1000 µg/mL showed decreasing early apoptosis: 28.69–32.16%, 12.59–18.84%, and 10.91–12.61%, respectively. The rest of the NHLF exposed to PE showed late apoptosis: 12.03–16–42%, 11.04–15.94%, and 49.23–51.28%. Statistical analysis showed a significance <em>P &lt;</em> 0.05 compared to the control.</p></div><div><h3>Conclusion</h3><p>The organic synthesis route of PE allows obtaining <em>rac</em>-1,2-<em>O</em>-Dipalmitoyl-glycero-3-phosphoethanolamine (<strong>1</strong>), which showed an apoptotic effect on NHLF.</p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"257 ","pages":"Article 105349"},"PeriodicalIF":3.4,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0009308423000713/pdfft?md5=6fc80b27b1609f8fc8647a5bd1aa75f7&pid=1-s2.0-S0009308423000713-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41186897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}