Arachidonic acid and free fatty acids as second messengers and the role of protein kinase C

Khan, Wasiuddin A.; Blobe, Gerard C.; Hannun, Yusuf A.

doi:10.1016/0898-6568(94)00089-t

Cited by 225Protein Kinase Regulation and GTPase SignalingSphingolipid Metabolism and SignalingFatty Acid Research and Health

Arachidonic acid and free fatty acids as second messengers and the role of protein kinase C

Khan, Wasiuddin A., Blobe, Gerard C., Hannun, Yusuf A.·1995·Cellular Signalling

DOI 10.1016/0898-6568(94)00089-t

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Abstract

In addition to serving as the precursor to a plethora of eicosanoids and other bioactive molecules, arachidonate may function as a bona fide second messenger. A number of studies have documented the ability of arachidonate to regulate the function of multiple targets in vitro systems. This has been particularly well established and studied with the activation of protein kinase C by arachidonate in a mechanism distinct from activation by diacylglycerol. In cells, arachidonate induces a number of activities, many of which may be independent of further metabolism to eicosanoids; suggesting possible direct action of arachidonate. This review summarizes the current state of knowledge on the possible second messenger function of arachidonate with specific emphasis on the regulation of protein kinase C.

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Self-citation
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Mitosis in hepatocytes is generally associated with elevated levels of the target polypeptide of a liver carcinogen
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Evidence that Arachidonic Acid Influences Hen Granulosa Cell Steroidogenesis and Plasminogen Activator Activity by a Protein Kinase C-Independent Mechanism1
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Glutamate uptake
Danbolt, N. C. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(00)00067-8 · Cited by 4,068 · see citing works
Antibacterial free fatty acids: activities, mechanisms of action and biotechnological potential
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Regulation of protein kinase C
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Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids.
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Apoptosis: A Functional Paradigm for Programmed Plant Cell Death Induced by a Host-Selective Phytotoxin and Invoked during Development.
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The Sevenfold Way of PKC Regulation
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Endocannabinoids
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Green Fluorescent Protein (GFP)-tagged Cysteine-rich Domains from Protein Kinase C as Fluorescent Indicators for Diacylglycerol Signaling in Living Cells
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Hydrogen Peroxide as a Cell-Survival Signaling Molecule
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The Unique Molecular and Cellular Microenvironment of Ovarian Cancer
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Arachidonic Acid Stimulates Prostate Cancer Cell Growth: Critical Role of 5-Lipoxygenase
Ghosh, J., & Myers, C. E. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.6799 · Cited by 259 · see citing works
Novel Roles of Specific Isoforms of Protein Kinase C in Activation of the c-fosSerum Response Element
Soh, J., Lee, E. H., Prywes, R., & Weinstein, I. B. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.2.1313 · Cited by 259 · see citing works
Pathogenesis of cerebral vasospasm following aneurysmal subarachnoid hemorrhage: Putative mechanisms and novel approaches
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Solvent-free matrix dry-coating for MALDI imaging of phospholipids
Puolitaival, S. M., Burnum-Johnson, K., Cornett, D. S., & Caprioli, R. M. (2008) · Journal of the American Society for Mass Spectrometry · doi:10.1016/j.jasms.2008.02.013 · Cited by 228 · see citing works
Fatty Acids and Immune Responses—A New Perspective in Searching for Clues to Mechanism
Hwang, D. H. (2000) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.20.1.431 · Cited by 204 · see citing works
Effects of fatty acid unsaturation numbers on membrane fluidity and α-secretase-dependent amyloid precursor protein processing
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Fumonisin-induced hepatocarcinogenesis: mechanisms related to cancer initiation and promotion.
Gelderblom, W. C. A., Abel, S., Smuts, C. M., Marnewick, J. L., Marasas, W. F. O., Lemmer, E. R., & Ramljak, D. (2001) · Environmental Health Perspectives · doi:10.1289/ehp.01109s2291 · Cited by 192 · see citing works
20-Hydroxyeicosatetraenoic Acid-induced Vasoconstriction and Inhibition of Potassium Current in Cerebral Vascular Smooth Muscle Is Dependent on Activation of Protein Kinase C
Lange, A. R., Gebremedhin, D., Narayanan, J., & Harder, D. R. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.43.27345 · Cited by 186 · see citing works
Interrelationships between astrocyte function, oxidative stress and antioxidant status within the central nervous system
Peuchen, S., Bolaños, J. P., Heales, S., Almeida, Á., Duchen, M. R., & Clark, J. B. (1997) · Progress in Neurobiology · doi:10.1016/s0301-0082(97)00010-5 · Cited by 160 · see citing works
Spatial and temporal alterations of phospholipids determined by mass spectrometry during mouse embryo implantation
Burnum-Johnson, K., Cornett, D. S., Puolitaival, S. M., Milne, S. B., Myers, D. S., Tranguch, S. L., Brown, H. A., Dey, S. K., & Caprioli, R. M. (2009) · Journal of Lipid Research · doi:10.1194/jlr.m900100-jlr200 · Cited by 158 · see citing works
20-Hydroxyeicosa-tetraenoic acid (20 HETE) activates protein kinase C. Role in regulation of rat renal Na+,K+-ATPase.
Nowicki, S., Chen, S. L., Aizman, O., Cheng, X.-J., Li, D., Nowicki, C., Nairn, A. C., Greengard, P., & Aperia, A. C. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119279 · Cited by 153 · see citing works
Arachidonic Acid Promotes Phosphorylation of 5-Lipoxygenase at Ser-271 by MAPK-activated Protein Kinase 2 (MK2)
Werz, O., Szellas, D., Steinhilber, D., & Rådmark, O. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111945200 · Cited by 130 · see citing works
Pharmacology of signaling induced by dopamine D1-like receptor activation
Undieh, A. S. (2010) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2010.05.003 · Cited by 128 · see citing works
Peroxisome Proliferator–Activated Receptors: A Critical Link among Fatty Acids, Gene Expression and Carcinogenesis
Heuvel, J. P. V. (1999) · Journal of Nutrition · doi:10.1093/jn/129.2.575s · Cited by 124 · see citing works
Protein kinase C: a physiological mediator of enhanced transmitter output
Majewski, H., & Iannazzo, L. (1998) · Progress in Neurobiology · doi:10.1016/s0301-0082(98)00017-3 · Cited by 116 · see citing works
Imaging of Intact Tissue Sections: Moving beyond the Microscope
Seeley, E. H., Schwamborn, K., & Caprioli, R. M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.r111.225854 · Cited by 111 · see citing works
A transcriptome-based global map of signaling pathways in the ovarian cancer microenvironment associated with clinical outcome
Reinartz, S., Finkernagel, F., Adhikary, T., Rohnalter, V., Schumann, T., Schober, Y., Nockher, W. A., Nist, A., Stiewe, T., Jansen, J. M., et al. (2016) · Genome biology · doi:10.1186/s13059-016-0956-6 · Cited by 109 · see citing works
The molecular biology of the group VIA Ca2+-independent phospholipase A2
Ma, Z., & TURK, J. W. (2001) · Progress in nucleic acid research and molecular biology · doi:10.1016/s0079-6603(01)67023-5 · Cited by 106 · see citing works
Isoenzymes of protein kinase C: differential involvement in apoptosis and pathogenesis.
Deacon, E. M., Pongracz, J. E., Griffiths, G., & Lord, J. M. (1997) · Molecular Pathology · doi:10.1136/mp.50.3.124 · Cited by 104 · see citing works
Ca2+ influx through CRAC channels activates cytosolic phospholipase A 2 , leukotriene C 4 secretion, and expression of c‐fos through ERK‐dependent and independent pathways in mast cells
Chang, W., Nelson, C., & Parekh, A. B. (2006) · The FASEB Journal · doi:10.1096/fj.06-6016fje · Cited by 102 · see citing works
Assessment of the arachidonic acid content in foods commonly consumed in the American diet
Taber, L., Chiu, C., & Whelan, J. (1998) · Lipids · doi:10.1007/s11745-998-0317-4 · Cited by 101 · see citing works
Role of polyunsaturated fatty acids in the inhibitory effect of human adipocytes on osteoblastic proliferation
Maurin, A., Chavassieux, P., Véricel, E., & Meunier, P. J. (2002) · Bone · doi:10.1016/s8756-3282(02)00805-0 · Cited by 100 · see citing works
Novel, selective delta6 or delta5 fatty acid desaturase inhibitors as antiinflammatory agents in mice.
Obukowicz, M. G., Welsch, D., Salsgiver, W. J., Martin-Berger, C. L., Chinn, K. S., Duffin, K. L., Raz, A., & Needleman, P. (1998) · PubMed · Cited by 100 · see citing works
Regulation of Rat Hepatocyte Protein Kinase C β Isoenzymes by the Lipid Peroxidation Product 4–Hydroxy–2,3–Nonenal: A Signaling Pathway to Modulate Vesicular Transport of Glycoproteins
Chiarpotto, E., Domenicotti, C., Paola, D., Vitali, A., Nitti, M., Pronzato, M. A., Biasi, F., Cottalasso, D., Marinari, U. M., Dragonetti, A., et al. (1999) · Hepatology · doi:10.1002/hep.510290510 · Cited by 97 · see citing works
A New Phosphatidylinositol 4,5-Bisphosphate-binding Site Located in the C2 Domain of Protein Kinase Cα*
Corbalán-García, S., García-García, J., Rodriguez-Alfaro, J. A., & Gomez-Fernandez, J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209385200 · Cited by 99 · see citing works
Receptor-mediated signaling pathways: potential targets of modulation by dietary fatty acids
Hwang, D., & Rhee, S. H. (1999) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/70.4.545 · Cited by 96 · see citing works
Prostaglandin E2 regulation of cyclooxygenase expression in keratinocytes is mediated via cyclic nucleotide-linked prostaglandin receptors
Maldve, R. E., Kim, Y., Muga, S. J., & Fischer, S. M. (2000) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)32029-0 · Cited by 96 · see citing works
A causal relationship between unscheduled eicosanoid signaling and tumor development: cancer chemoprevention by inhibitors of arachidonic acid metabolism
Marks, F., Müller‐Decker, K., & Fürstenberger, G. (2000) · Toxicology · doi:10.1016/s0300-483x(00)00301-2 · Cited by 94 · see citing works
Effects of partial substitution of dietary fish oil with blends of vegetable oils, on blood leucocyte fatty acid compositions, immune function and histology in European sea bass (Dicentrarchus labrax L.)
Mourente, G., Good, J. E., Thompson, K. D., & Bell, J. G. (2007) · British Journal Of Nutrition · doi:10.1017/s000711450773461x · Cited by 93 · see citing works
Carnitine inhibits arachidonic acid turnover, platelet function, and oxidative stress
Pignatelli, P., Lenti, L., Sanguigni, V., Frati, G., Simeoni, I., Gazzaniga, P. P., Pulcinelli, F. M., & Violi, F. (2003) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00249.2002 · Cited by 92 · see citing works
How lipids contribute to ion channel function, a fat perspective on direct and indirect interactions
Cordero-Morales, J. F., & Vásquez, V. (2018) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2018.03.015 · Cited by 91 · see citing works
Eicosapentaenoic acid reduces ABCA1 serine phosphorylation and impairs ABCA1-dependent cholesterol efflux through cyclic AMP/protein kinase A signaling pathway in THP-1 macrophage-derived foam cells
Hu, Y., Ma, X., Li, X., Liu, X., Xiao, J., Mo, Z., Xiang, J., Liao, D., & Tang, C. (2008) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2008.11.003 · Cited by 89 · see citing works
Close Functional Coupling between Ca2+ Release-activated Ca2+ Channels, Arachidonic Acid Release, and Leukotriene C4 Secretion
Chang, W., & Parekh, A. B. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403969200 · Cited by 86 · see citing works
Rapid quantitation of free fatty acids in human plasma by high-performance liquid chromatography
Mehta, A., Oeser, A. M., & Carlson, M. G. (1998) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/s0378-4347(98)00403-4 · Cited by 83 · see citing works
Eicosapentaenoic Acid, a n-3 Polyunsaturated Fatty Acid Differentially Modulates TNF-α, IL-1α, IL-6 and PGE2 Expression in UVB-Irradiated Human Keratinocytes
Pupe, A., Haes, P. D., Rhodes, L. E., Garmyn, M., Moison, R. M. W., van Henegouwen, G. B., & Degreef, H. J. (2002) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2002.01615.x · Cited by 82 · see citing works
Cyclooxygenase-2 and prostaglandin signaling in cholangiocarcinoma
Wu, T. (2005) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2005.04.002 · Cited by 81 · see citing works
Regulation of plasma fatty acid metabolism
Saleh, J., Sniderman, A. D., & Cianflone, K. (1999) · Clinica Chimica Acta · doi:10.1016/s0009-8981(99)00099-6 · Cited by 81 · see citing works
Silencing the expression of mitochondrial acyl-CoA thioesterase I and acyl-CoA synthetase 4 inhibits hormone-induced steroidogenesis
Maloberti, P., Castilla, R., Castillo, F., Maciel, F. C., Mendez, C. F., Paz, C., & Podestá, E. J. (2005) · The FEBS Journal · doi:10.1111/j.1742-4658.2005.04616.x · Cited by 79 · see citing works
Arachidonic Acid Influences Proinflammatory Gene Induction by Stabilizing the Inhibitor-κBα/Nuclear Factor-κB (NF-κB) Complex, thus Suppressing the Nuclear Translocation of NF-κB
Stuhlmeier, K. M., Kao, J. J., & Bach, F. H. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.39.24679 · Cited by 78 · see citing works
Activation of Epithelial Growth Factor Receptor Pathway by Unsaturated Fatty Acids
Vacaresse, N., Lajoie‐Mazenc, I., Augè, N., Suc, I., Frisach, M., Salvayre, R., & Nègre‐Salvayre, A. (1999) · Circulation Research · doi:10.1161/01.res.85.10.892 · Cited by 77 · see citing works
Cellular Regulation of Cytosolic Group IV Phospholipase A2 by Phosphatidylinositol Bisphosphate Levels
Balsinde, J., Balboa, M. A., Li, W.-H., Llopis, J. L., & Dennis, E. A. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.10.5398 · Cited by 77 · see citing works
Activation of neutral sphingomyelinase in human neutrophils by polyunsaturated‘qc fatty acids
Robinson, B. S., Hii, C. S. T., Poulos, A., & Ferrante, A. (1997) · Immunology · doi:10.1046/j.1365-2567.1997.d01-2227.x · Cited by 77 · see citing works
Putative neuroprotective actions of N-acyl-ethanolamines
Hansen, H. S., Moesgaard, B., Petersen, G. L., & Hansen, H. H. (2002) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(02)00251-6 · Cited by 73 · see citing works
Phospholipases of Mineralization Competent Cells and Matrix Vesicles: Roles in Physiological and Pathological Mineralizations
Mebarek, S., Abousalham, A., Magne, D., Do, L.-D., Bandorowicz‐Pikuła, J., Pikuła, S., & Buchet, R. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms14035036 · Cited by 69 · see citing works
The role of lipids and protein kinase Cs in the pathogenesis of diabetic retinopathy
Curtis, T., & Scholfield, C. (2004) · Diabetes/Metabolism Research Reviews · doi:10.1002/dmrr.431 · Cited by 77 · see citing works
Modulation of phosphoinositide–protein kinase C signal transduction by omega-3 fatty acids: Implications for the pathophysiology and treatment of recurrent neuropsychiatric illness
McNamara, R. K., Ostrander, M. M., Abplanalp, W. A., Richtand, N. M., Benoit, S. C., & Clegg, D. J. (2006) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2006.07.009 · Cited by 70 · see citing works
Long‐chain polyunsaturated fatty acids and eicosanoids in infants‐physiological and pathophysiological aspects and open questions
Sellmayer, A., & Koletzko, B. V. (1999) · Lipids · doi:10.1007/s11745-999-0354-z · Cited by 69 · see citing works
Changes in essential fatty acid patterns associated with normal liver regeneration and the progression of hepatocyte nodules in rat hepatocarcinogenesis
Abel, S. (2001) · Carcinogenesis · doi:10.1093/carcin/22.5.795 · Cited by 68 · see citing works
The heterodimer of the Ca2+‐binding proteins MRP8 and MRP14 binds arachidonic acid
Klempt, M., Melkonyan, H., Nacken, W. K. F., Wiesmann, D., Holtkemper, U., & Sorg, C. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)00394-3 · Cited by 68 · see citing works
Stimulation of GLP-1 Secretion Downstream of the Ligand-Gated Ion Channel TRPA1
Emery, E. C., Diakogiannaki, E., Gentry, C., Psichas, A., Habib, A. M., Bevan, S., Fischer, M. J. M., Reimann, F. M., & Gribble, F. M. (2014) · Diabetes · doi:10.2337/db14-0737 · Cited by 67 · see citing works
Mitochondrial oxidative stress is modulated by oleic acid via an epidermal growth factor receptor-dependent activation of glutathione peroxidase
Duval, C., Augè, N., Frisach, M., Casteilla, L., Salvayre, R., & Nègre‐Salvayre, A. (2002) · Biochemical Journal · doi:10.1042/bj20020625 · Cited by 66 · see citing works
Protein Kinases C Translocation Responses to Low Concentrations of Arachidonic Acid
O’Flaherty, J. T., Chadwell, B. A., Kearns, M. W., Sergeant, S., & Daniel, L. W. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101093200 · Cited by 64 · see citing works
Functional food science and the cardiovascular system
Hornstra, G., Barth, C. A., Galli, C. L., Mensink, R. P., Mutanen, M. L., Riemersma, R. A., Roberfroid, M. B., Salminen, K. R., Vansant, G. A. A. M., & Verschuren, P. M. (1998) · British Journal Of Nutrition · doi:10.1079/bjn19980107 · Cited by 63 · see citing works
SIGNAL TRANSDUCTION IN ENVIRONMENTAL NEUROTOXICITY
Costa, L. G. (1998) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.38.1.21 · Cited by 62 · see citing works
Arachidonic acid protects neonatal rat cardiac myocytes from ischaemic injury through ε protein kinase C
Mackay, K. (2001) · Cardiovascular Research · doi:10.1016/s0008-6363(00)00322-9 · Cited by 61 · see citing works
Identification and Characterization of a Novel Δ6/Δ5 Fatty Acid Desaturase Inhibitor As a Potential Anti-Inflammatory Agent
Obukowicz, M. G., Raz, A., Pyla, P. D., Rico, J. G., Wendling, J. M., & Needleman, P. (1998) · Biochemical Pharmacology · doi:10.1016/s0006-2952(97)00665-5 · Cited by 56 · see citing works
Long Chain n-3 Polyunsaturated Fatty Acids in the Prevention of Allergic and Cardiovascular Disease
van den Elsen, L. W. J., Garssen, J., & Willemsen, L. E. M. (2012) · Current Pharmaceutical Design · doi:10.2174/138161212800165960 · Cited by 54 · see citing works
Bioactive Lipid Signaling in Cardiovascular Disease, Development, and Regeneration
Wasserman, A. H., Venkatesan, M., & Aguirre, A. (2020) · Cells · doi:10.3390/cells9061391 · Cited by 50 · see citing works
Differential membrane binding and diacylglycerol recognition by C1 domains of RasGRPs
Johnson, J. E., Goulding, R. E., Ding, Z., Partovi, A., Anthony, K., Beaulieu, N., Tazmini, G., Cornell, R. B., & Kay, R. J. (2007) · Biochemical Journal · doi:10.1042/bj20070294 · Cited by 53 · see citing works
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Authors: Khan, W. A., Blobe, G. C., & Hannun, Y. A.
Affiliations: Duke Medical Center (US)
Duke University (US)
Corresponding author: Khan, Wasiuddin A.
ORCID: Blobe, Gerard C.
Hannun, Yusuf A.
Venue: Cellular Signalling
Publisher: Elsevier BV
Published: 1995-03
Volume: 7
Issue: 3
Pages: 171-184
ISSN: 0898-6568 (ISSN-L)
DOI: 10.1016/0898-6568(94)00089-t
OpenAlex: W2002668908
Cited by: 225
References: 105
Citations by year: 2025: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 3 · 2018: 6 · 2017: 2 · 2016: 5 · 2015: 5 · 2014: 4 · 2013: 7 · 2012: 2
FWCI: 7.56
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Cellular Signalling (publishedVersion)
PubMed (publishedVersion)
Funders: National Heart, Lung, and Blood Institute (HL43707, R01HL043707)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
Keywords: arachidonic acid, free fatty acids, second messengers, protein kinase C, eicosanoids, fatty acid signaling
MeSH terms: Animals, Enzyme Activation, Fatty Acids, Nonesterified, Homeostasis, Humans, Models, Biological, Protein Kinase C, Second Messenger Systems, Eicosanoids, Arachidonic Acid

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Arachidonic acid and free fatty acids as second messengers and the role of protein kinase C

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