Sequestration of 9-Hydroxystearic Acid in FAHFA (Fatty Acid Esters of Hydroxy Fatty Acids) as a Protective Mechanism for Colon Carcinoma Cells to Avoid Apoptotic Cell Death
Abstract
1. Introduction
2. Results and Discussion
3. Materials and Methods
3.1. Reagents
3.2. Patients and Sampling Procedures
3.3. Cell Lines
3.4. Detection of Apoptosis
3.5. Immunoblot Analyses
3.6. Real-Time PCR
3.7. Gas Chromatography/Mass Spectrometry (GC/MS) Analyses
3.8. Liquid Chromatography/Mass Spectrometry (LC/MS) Analyses
3.9. Statistical Analysis
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Araghi, M.; Soerjomataram, I.; Jenkins, M.; Brierley, J.; Morris, E.; Bray, F.; Arnold, M. Global trends in colorectal cancer mortality: Projections to the year 2035. Int. J. Cancer 2018, in press. [Google Scholar] [CrossRef] [PubMed]
- De Visser, K.E.; Eichten, A.; Coussens, L.M. Paradoxical roles of the immune system during cancer development. Nat. Rev. Cancer 2006, 6, 24–37. [Google Scholar] [CrossRef] [PubMed]
- Mohme, M.; Riethdorf, S.; Pantel, K. Circulating and disseminated tumour cells—Mechanisms of immune surveillance and escape. Nat. Rev. Clin. Oncol. 2016, 14, 155–167. [Google Scholar] [CrossRef] [PubMed]
- Ogretmen, B. Sphingolipid metabolism in cancer signalling and therapy. Nat. Rev. Cancer 2017, 18, 33–50. [Google Scholar] [CrossRef] [PubMed]
- Cavalli, G.; Casali, E.; Spisni, A.; Masotti, L. Identification of the peroxidation product hydroxystearic acid in Lewis lung carcinoma cells. Biochem. Biophys. Res. Commun. 1991, 178, 1260–1265. [Google Scholar] [CrossRef]
- Masotti, L.; Casali, E.; Gesmundo, N. Influence of hydroxystearic acid on in vitro cell proliferation. Mol. Asp. Med. 1993, 14, 209–215. [Google Scholar] [CrossRef]
- Calonghi, N.; Cappadone, C.; Pagnotta, E.; Farruggia, G.; Buontempo, F.; Boga, C.; Brusa, G.L.; Santucci, M.A.; Masotti, L. 9-Hydroxystearic acid upregulates p21WAF1 in HT29 cancer cells. Biochem. Biophys. Res. Commun. 2004, 314, 138–142. [Google Scholar] [CrossRef]
- Calonghi, N.; Cappadone, C.; Pagnotta, E.; Boga, C.; Bertucci, C.; Fiori, J.; Tasco, G.; Casadio, R.; Masotti, L. Histone deacetylase 1: A target of 9-hydroxystearic acid in the inhibition of cell growth in human colon cancer. J. Lipid Res. 2005, 46, 1596–1603. [Google Scholar] [CrossRef]
- Calonghi, N.; Pagnotta, E.; Parolin, C.; Tognoli, C.; Boga, C.; Masotti, L. 9-Hydroxystearic acid interferes with EGF signalling in a human colon adenocarcinoma. Biochem. Biophys. Res. Commun. 2006, 342, 585–588. [Google Scholar] [CrossRef]
- Parolin, C.; Calonghi, N.; Presta, E.; Boga, C.; Caruana, P.; Naldi, M.; Andrisano, V.; Masotti, L.; Sartor, G. Mechanism and stereoselectivity of HDAC inhibition by (R)-9-hydroxystearic acid in colon cancer. Biochim. Biophys. Acta 2012, 1821, 1334–1340. [Google Scholar] [CrossRef] [PubMed]
- Yore, M.M.; Syed, I.; Moraes-Vieira, P.M.; Zhang, T.; Herman, M.A.; Homan, E.A.; Patel, R.T.; Lee, J.; Chen, S.; Peroni, O.D.; et al. Discovery of a class of endogenous mammalian lipids with anti-diabetic and anti-inflammatory effects. Cell 2014, 159, 318–332. [Google Scholar] [CrossRef]
- Moraes-Vieira, P.M.; Saghatelian, A.; Kahn, B.B. GLUT4 expression in adipocytes regulates de novo lipogenesis and levels of a novel class of lipids with antidiabetic and anti-inflammatory effects. Diabetes 2016, 65, 1808–1815. [Google Scholar] [CrossRef]
- Fahy, E.; Subramaniam, S.; Brown, H.A.; Glass, C.K.; Merrill, A.H.; Murphy, R.C.; Raetz, C.R.; Russell, D.W.; Seyama, Y.; Shaw, W.; et al. A comprehensive classification system for lipids. J. Lipid Res. 2005, 46, 839–861. [Google Scholar] [CrossRef]
- Thomas, C.P.; Morgan, L.T.; Maskrey, B.H.; Murphy, R.C.; Kühn, H.; Hazen, S.L.; Goodall, A.H.; Hamali, H.A.; Collins, P.W.; O’Donnell, V.B. Phospholipid-esterified eicosanoids are generated in agonist-activated human platelets and enhance tissue factor-dependent thrombin generation. J. Biol. Chem. 2010, 285, 6891–6903. [Google Scholar] [CrossRef]
- Slatter, D.A.; Aldrovandi, M.; O’Connor, A.; Allen, S.M.; Brasher, C.J.; Murphy, R.C.; Mecklemann, S.; Ravi, S.; Darley-Usmar, V.; O’Donnell, V.B. Mapping the human platelet lipidome reveals cytosolic phospholipase A2 as a regulator of mitochondrial bioenergetics during activation. Cell Metab. 2016, 23, 930–944. [Google Scholar] [CrossRef]
- O’Donnell, V.B.; Murphy, R.C. Directing eicosanoid esterification into phospholipids. J. Lipid Res. 2017, 58, 837–839. [Google Scholar] [CrossRef]
- Pulfer, M.; Murphy, R.C. Electrospray mass spectrometry of phospholipids. Mass Spectrom. Rev. 2003, 22, 332–364. [Google Scholar] [CrossRef]
- Astudillo, A.M.; Balboa, M.A.; Balsinde, J. Selectivity of phospholipid hydrolysis by phospholipase A2 enzymes in activated cells leading to polyunsaturated fatty acid mobilization. Biochim. Biophys. Acta 2019, 1864, 772–783. [Google Scholar] [CrossRef]
- Casas, J.; Gijón, M.A.; Vigo, A.G.; Crespo, M.S.; Balsinde, J.; Balboa, M.A. Phosphatidylinositol 4, 5-bisphosphate anchors cytosolic group IVA phospholipase A2 to perinuclear membranes and decreases its calcium requirement for translocation in live cells. Mol. Biol. Cell 2006, 17, 155–162. [Google Scholar] [CrossRef]
- Guijas, C.; Rodríguez, J.P.; Rubio, J.M.; Balboa, M.A.; Balsinde, J. Phospholipase A2 regulation of lipid droplet formation. Biochim. Biophys. Acta 2014, 1841, 1661–1671. [Google Scholar] [CrossRef]
- Ruipérez, V.; Astudillo, A.M.; Balboa, M.A.; Balsinde, J. Coordinate regulation of Toll-like receptor- mediated arachidonic acid mobilization in macrophages by group IVA and group V phospholipase A2s. J. Immunol. 2009, 182, 3877–3883. [Google Scholar] [CrossRef]
- Rubio, J.M.; Rodríguez, J.P.; Gil-de-Gómez, L.; Guijas, C.; Balboa, M.A.; Balsinde, J. Group V secreted phospholipase A2 is up-regulated by interleukin-4 in human macrophages and mediates phagocytosis via hydrolysis of ethanolamine phospholipids. J. Immunol. 2015, 194, 3327–3339. [Google Scholar] [CrossRef]
- Zhang, J.; Zhang, L.; Ye, X.; Chen, L.; Zhang, L.; Gao, Y.; Kang, J.X.; Cai, C. Characteristics of fatty acid distribution is associated with colorectal cancer prognosis. Prostag. Leukot. Essent. Fat. Acids 2013, 88, 355–360. [Google Scholar] [CrossRef]
- Bevers, L.E.; Pinkse, M.W.H.; Verhaert, P.D.E.M.; Hagen, W.R. Oleate hydratase catalyzes the hydration of a nonactivated carbon-carbon bond. J. Bacteriol. 2009, 191, 5010–5012. [Google Scholar] [CrossRef]
- Morvan, B.; Joblin, K.N. Hydration of oleic acid by Enterococcus gallinarum, Pediococcus acidilactici and Lactobacillus sp. isolated from the rumen. Anaerobe 1999, 5, 605–611. [Google Scholar] [CrossRef]
- Wilson, R.; Lyall, K.; Smyth, L.; Fernie, C.E.; Riemersma, R.A. Dietary hydroxy fatty acids are absorbed in humans: Implications for the measurement of “oxidative stress” in vivo. Free Radic. Biol. Med. 2002, 32, 162–168. [Google Scholar] [CrossRef]
- Kuda, O.; Brezinova, M.; Silhavy, J.; Landa, V.; Zidek, V.; Dodia, C.; Kreuchwig, F.; Vrbacky, M.; Balas, L.; Durand, T.; et al. Nrf2-mediated antioxidant defense and peroxiredoxin 6 are linked to biosynthesis of palmitic acid ester of 9-hydroxystearic acid. Diabetes 2018, 67, 1190–1199. [Google Scholar] [CrossRef]
- Balas, L.; Feillet-Coudray, C.; Durand, T. Branched fatty acyl esters of hydroxyl fatty acids, appealing beneficial endogenous fat against obesity and type-2 diabetes. Chem. Eur. J. 2018, 24, 9463–9476. [Google Scholar] [CrossRef]
- Nelson, A.T.; Kolar, M.J.; Chu, Q.; Syed, I.; Kahn, B.B.; Saghatelian, A.; Siegel, D. Stereochemistry of endogenous palmitic acid ester of 9-hydroxystearic acid and relevance of absolute configuration to regulation. J. Am. Chem. Soc. 2017, 139, 4943–4947. [Google Scholar] [CrossRef]
- Boulares, A.H.; Yakovlev, A.G.; Ivanova, V.; Stoica, B.A.; Wang, G.; Iyer, S.; Smulson, M. Role of poly(ADP-ribose) polymerase (PARP) cleavage in apoptosis. Caspase-3-resistant PARP mutant increases rates of apoptosis in transfected cells. J. Biol. Chem. 1999, 274, 22932–22940. [Google Scholar] [CrossRef]
- Pérez, R.; Matabosch, X.; Llebaria, A.; Balboa, M.A.; Balsinde, J. Blockade of arachidonic acid incorporation into phospholipids induces apoptosis in U937 promonocytic cells. J. Lipid Res. 2006, 47, 484–491. [Google Scholar] [CrossRef]
- Valdearcos, M.; Esquinas, E.; Meana, C.; Peña, L.; Gil-de-Gómez, L.; Balsinde, J.; Balboa, M.A. Lipin-2 reduces proinflammatory signaling induced by saturated fatty acids in macrophages. J. Biol. Chem. 2012, 287, 10894–10904. [Google Scholar] [CrossRef]
- Folch, J.; Lees, M.; Sloane Stanley, G.H. A simple method for the isolation and purification of total lipides from animal tissues. J. Biol. Chem. 1957, 226, 497–509. [Google Scholar]
- Bligh, E.G.; Dyer, W.J. A rapid method of total lipid extraction and purification. Can. J. Biochem. Physiol. 1959, 37, 911–917. [Google Scholar] [CrossRef] [PubMed]
- Diez, E.; Balsinde, J.; Aracil, M.; Schüller, A. Ethanol induces release of arachidonic acid but not synthesis of eicosanoids in mouse peritoneal macrophages. Biochim. Biophys. Acta 1987, 921, 82–89. [Google Scholar] [CrossRef]
- Astudillo, A.M.; Pérez-Chacón, G.; Balgoma, D.; Gil-de-Gómez, L.; Ruipérez, V.; Guijas, C.; Balboa, M.A.; Balsinde, J. Influence of cellular arachidonic acid levels on phospholipid remodeling and CoA-independent transacylase activity in human monocytes and U937 cells. Biochim. Biophys. Acta 2011, 1811, 97–103. [Google Scholar] [CrossRef]
- Guijas, C.; Pérez-Chacón, G.; Astudillo, A.M.; Rubio, J.M.; Gil-de-Gómez, L.; Balboa, M.A.; Balsinde, J. Simultaneous activation of p38 and JNK by arachidonic acid stimulates the cytosolic phospholipase A2-dependent synthesis of lipid droplets in human monocytes. J. Lipid Res. 2012, 53, 2343–2354. [Google Scholar] [CrossRef] [PubMed]
- Guijas, C.; Meana, C.; Astudillo, A.M.; Balboa, M.A.; Balsinde, J. Foamy monocytes are enriched in cis-7-hexadecenoic fatty acid, 16:1n-9, a possible biomarker for early detection of cardiovascular disease. Cell Chem. Biol. 2016, 23, 689–699. [Google Scholar] [CrossRef]
- Astudillo, A.M.; Meana, C.; Guijas, C.; Pereira, L.; Lebrero, P.; Balboa, M.A.; Balsinde, J. Occurrence and biological activity of palmitoleic acid isomers in phagocytic cells. J. Lipid Res. 2018, 59, 237–249. [Google Scholar] [CrossRef]
- Balgoma, D.; Astudillo, A.M.; Pérez-Chacón, G.; Montero, O.; Balboa, M.A.; Balsinde, J. Markers of monocyte activation revealed by lipidomic profiling of arachidonic acid-containing phospholipids. J. Immunol. 2010, 184, 3857–3865. [Google Scholar] [CrossRef] [PubMed]
- Astudillo, A.M.; Pérez-Chacón, G.; Meana, C.; Balgoma, D.; Pol, A.; del Pozo, M.A.; Balboa, M.A.; Balsinde, J. Altered arachidonate distribution in macrophages from caveolin-1 null mice leading to reduced eicosanoid synthesis. J. Biol. Chem. 2011, 286, 35299–35307. [Google Scholar] [CrossRef]
- Valdearcos, M.; Esquinas, E.; Meana, C.; Gil-de-Gómez, L.; Guijas, C.; Balsinde, J.; Balboa, M.A. Subcellular localization and role of lipin-1 in human macrophages. J. Immunol. 2011, 186, 6004–6013. [Google Scholar] [CrossRef]
- Gil-de-Gómez, L.; Astudillo, A.M.; Meana, C.; Rubio, J.M.; Guijas, C.; Balboa, M.A.; Balsinde, J. A phosphatidylinositol species acutely generated by activated macrophages regulates innate immune responses. J. Immunol. 2013, 190, 5169–5177. [Google Scholar] [CrossRef]
- Gil-de-Gómez, L.; Astudillo, A.M.; Guijas, C.; Magrioti, V.; Kokotos, G.; Balboa, M.A.; Balsinde, J. Cytosolic group IVA and calcium-independent group VIA phospholipase A2s act on distinct phospholipid pools in zymosan-stimulated mouse peritoneal macrophages. J. Immunol. 2014, 192, 752–762. [Google Scholar] [CrossRef]
- Gil-de-Gómez, L.; Astudillo, A.M.; Lebrero, P.; Balboa, M.A.; Balsinde, J. Essential role for ethanolamine plasmalogen hydrolysis in bacterial lipopolysaccharide priming of macrophages for enhanced arachidonic acid release. Front. Immunol. 2017, 8, 1251. [Google Scholar] [CrossRef]
- Rubio, J.M.; Astudillo, A.M.; Casas, J.; Balboa, M.A.; Balsinde, J. Regulation of phagocytosis in macrophages by membrane ethanolamine plasmalogens. Front. Immunol. 2018, 9, 1723. [Google Scholar] [CrossRef]
- Zhang, T.; Chen, S.; Syed, I.; Stáhlman, M.; Kolar, M.J.; Homan, E.A.; Chu, Q.; Smith, U.; Borén, J.; Kahn, B.B.; et al. A LC-MS–based workflow for measurement of branched fatty acid esters of hydroxy fatty acids. Nat. Protoc. 2016, 11, 747–763. [Google Scholar] [CrossRef]
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Rodríguez, J.P.; Guijas, C.; Astudillo, A.M.; Rubio, J.M.; Balboa, M.A.; Balsinde, J. Sequestration of 9-Hydroxystearic Acid in FAHFA (Fatty Acid Esters of Hydroxy Fatty Acids) as a Protective Mechanism for Colon Carcinoma Cells to Avoid Apoptotic Cell Death. Cancers 2019, 11, 524. https://doi.org/10.3390/cancers11040524
Rodríguez JP, Guijas C, Astudillo AM, Rubio JM, Balboa MA, Balsinde J. Sequestration of 9-Hydroxystearic Acid in FAHFA (Fatty Acid Esters of Hydroxy Fatty Acids) as a Protective Mechanism for Colon Carcinoma Cells to Avoid Apoptotic Cell Death. Cancers. 2019; 11(4):524. https://doi.org/10.3390/cancers11040524
Chicago/Turabian StyleRodríguez, Juan P., Carlos Guijas, Alma M. Astudillo, Julio M. Rubio, María A. Balboa, and Jesús Balsinde. 2019. "Sequestration of 9-Hydroxystearic Acid in FAHFA (Fatty Acid Esters of Hydroxy Fatty Acids) as a Protective Mechanism for Colon Carcinoma Cells to Avoid Apoptotic Cell Death" Cancers 11, no. 4: 524. https://doi.org/10.3390/cancers11040524
APA StyleRodríguez, J. P., Guijas, C., Astudillo, A. M., Rubio, J. M., Balboa, M. A., & Balsinde, J. (2019). Sequestration of 9-Hydroxystearic Acid in FAHFA (Fatty Acid Esters of Hydroxy Fatty Acids) as a Protective Mechanism for Colon Carcinoma Cells to Avoid Apoptotic Cell Death. Cancers, 11(4), 524. https://doi.org/10.3390/cancers11040524