Nicolas Bazan Explained

Nicolas G. Bazan, neuroscientist, eye researcher, and author. His research focuses on neurodegenerative diseases, neuroinflammation (inflammation of nervous tissue), and cell survival using cellular, molecular, and disease models including lipidomics. He also operates "Nicholas Bazan Wines" with Mark Wahle.

Appointments

• The Ernest C. and Yvette C. Villere Chair for Research in Retinal Degeneration - Louisiana State University Health Sciences Center (LSUHSC), New Orleans, LA, 1984-
• Professor of Ophthalmology, Biochemistry and Molecular Biology and Neurology, Louisiana State University Health Sciences Center (LSUHSC), School of Medicine, New Orleans, LA, 1981-
• Director (Founder), Neuroscience Center of Excellence, LSUHSC, School of Medicine, New Orleans, LA, 1988-
• Boyd Professor, Louisiana State University Health Sciences Center (LSUHSC), New Orleans, LA, 1994-
• Editor-in-Chief, Molecular Neurobiology (Springer), 1986-
• Senate Member, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) (German Center for Neurodegenerative Diseases) in der Helmholtz-Gemeinschaft, nationwide research program (Germany), 2009-
• Editorial Board, Cell Death, and Disease, Nature Publishing Group, 2010-
• Editorial Board, Cell Death, and Differentiation, Nature Publishing Group, 2011-
• Member, Biology of the Visual System Study Section, NIH, 2012-
• Chair of the Louisiana State University Health Sciences Center (LSUHSC) Research Council/Translational Research Initiative, New Orleans

Early life and education

Nicolas G. Bazan was born in Los Sarmientos, Tucuman, Argentina on May 22, 1942. He received his MD from the University of Tucuman School of Medicine, Argentina (1965) and was a postdoctoral fellow at Columbia University's College of Physicians and Surgeons and Harvard Medical School (1965–1968). The research that he performed at Harvard was the basis for his Doctorate in Medical Sciences thesis (University of Tucuman, 1971). He became the founding director of the Louisiana State University Heath Sciences Center (LSUHSC) Neuroscience Center of Excellence in 1989.

Scientific contributions

• Bazan demonstrated that brain ischemia, a condition that involves reduced blood flow to the brain, triggers the release of free essential fatty acids (arachidonic and docosahexaenoic acid) from membranes during seizures and ischemia through the enzyme phospholipase A2.^{[1] [2]} This finding has been referred to as the "Bazan Effect".^{[3] [4]}
• In the early 70's, his laboratory isolated a diacylglycerol containing docosahexaenoyl chains in C1 and C2 from the retina, demonstrated that this lipid is present in this tissue in relatively large proportions,^{[5] [6]} and uncovered novel molecular species of phospholipids (containing two docosahexaenoyl chains; coined the term "supraenoic" molecular species) displaying very rapid turnover.^{[7] [8] [9]}
• In 1975, he and his colleagues showed that the brains of newborn mammals and organisms that cannot regulate their own body temperature accumulate free arachidonic acid sluggishly, correlating with the known resistance of these animals to anoxia. In contrast, animals that are able to regulate body temperature are vulnerable to relatively short periods of a severe absence of oxygen, rapidly accumulate arachidonic and docosahexaenoic acid as a result of phospholipase A2 activation.^[10] Also, his laboratory found that the diacylglycerol accumulated in the brain during ischemia is derived from inositol lipids and postulated that selective vulnerability at synapses engages the degradation of inositol lipids.^[11]
• In 1980, he and his colleagues described those molecular species of phospholipids in photoreceptors contain two docosahexaenoyl chains per molecule, rather than a saturated chain at C1 and an unsaturated chain at C2, confirming their initial observation of the 70s.^[12] Also, he and his colleagues identified inositol lipid degradation and phospholipase A2 activation in neural cell damage in experimental epilepsy and stroke.^{[13] [14] [15] [16] [17] [18] [19]}
• He and his colleagues showed in 1979 that phospholipase A2 activation, which gives rise to brain-free arachidonic and docosahexaenoic acid upon stimulation, is related to neurotransmission. In addition, he showed that the concept commonly described in textbooks, that the essential fatty acid docosahexaenoic acid is introduced through the acylation-deacylation cycle in retina membranes (and in other excitable membranes), is incorrect. Rather, they demonstrated that this fatty acid is introduced to a large extent through the de novo synthesis of phosphatidic acid.^{[20] [21] [22] [23]}
• His laboratory later identified an activating enzyme for docosahexaenoic acid with very low Km, which allows photoreceptors and other excitable membranes to retain this fatty acid.^{[24] [25]} Also in a series of studies, they found that leukotrienes, HETEs (hydroxyeicosatetraenoic acids), inositol lipids, and prostaglandins are key molecules in the communication between retinal pigment epithelial cells and photoreceptors.^{[26] [27] [28] [29]}
• In 1985, Bazan and his colleagues provided evidence that retinal pigment epithelial cells retain docosahexaenoic acid within photoreceptors by a "short loop" between both cells, and a "long loop" between the liver and the retina.^{[30] [31] [32] [33] [34] [35] [36] [37] [38] [39]} His laboratory further supported these concepts by demonstrating a deficit of docosahexaenoic and arachidonic acid in Usher's syndrome.^[40] Then they demonstrated that phagocytosis by retinal pigment epithelial cells induces gene expression.^[41] During that time, Bazan and his colleagues found prostaglandin D synthetase in the interphotoreceptor matrix and cloned its receptor.^[42] They demonstrated that docosahexaenoic acid is transported from the post-Golgi network to the photoreceptor disk membranes with rhodopsin.^[43]
• Bazan and colleagues also showed that platelet-activating factor (PAF) is an endogenous neurotoxin and demonstrated neuroprotection by PAF antagonists.^{[44] [45]} This included the finding that seizure-induced platelet-activating factor production activates gene expression,^{[46] [47] [48] [49]} as well as a new neuroprotection site, the PAF receptor. Moreover, his laboratory found that PAF modulates glutamate release and is a retrograde messenger of long-term potentiation and that this "physiological PAF" enhances memory formation.^{[50] [51] [52] [53]} Moreover, they found that PAF activates transcription of the inducible prostaglandin synthase, cyclooxygenase-2 (COX-2).^{[54] [55]}
• Subsequently, the Bazan laboratory demonstrated that secretory phospholipase A2 modulates neuronal survival and glutamate transmission.^{[56] [57] [58]} Then, Bazan's laboratory in collaboration with the Stephen Prescott lab showed that neuronal diacylglycerol kinase epsilon is necessary in seizures and neuroprotection.^[59] In 2002 they showed that photoreceptors have a DNA repair mechanism that is induced by light damage^[60] and identified that genes are upregulated in models of retinal pathoangiogenesis.^[61]
• In 2003, Bazan and his colleagues coined the term "docosanoids," which are enzyme-derived oxygenated messengers of docosahexaenoic acid, and in 2004 participated in the discovery of the synthesis and bioactivity of the first docosanoid, neuroprotectin D1 (NPD1). This paper relates how he and his colleagues discovered that NPD1 arrests apoptosis in retinal pigment epithelial cells at the pre-mitochondrial level.^{[62] [63] [64] [65] [66] [67] [68] [69]}
• In 2011 Bazan and his colleagues found that DHA is neuroprotective in experimental stroke and that NPD1 is neuroprotective in experimental epilepsy.^[70]
• Research led by Bazan in 2015 also discovered a protein in the retina that is crucial for vision. Bazan and his colleagues reported on the key molecular mechanisms leading to visual degeneration and blindness.^[71] They discovered that adiponectin receptor 1 (AdipoR1) is a regulator of these RPE cell functions and demonstrated that AdipoR1 ablation results in DHA reduction. These results established AdipoR1 as a regulatory switch of DHA uptake, retention, conservation, and elongation in photoreceptors and RPE cells, thus preserving photoreceptor cell integrity.^[72]
• In 2015 Bazan and his colleagues also discovered gene interactions that determine whether cells live or die in such conditions as age-related macular degeneration and ischemic stroke. They worked with human RPE cells and an experimental model of ischemic stroke and discovered novel mechanisms in cells with the ability to activate pathways that crosstalk one to another and then assemble consolidated responses that decide cell fate.^[73] The study reported that, in retinal pigment epithelial cells, NPD1 induces nuclear translocation and cREL synthesis that, in turn, mediates BIRC3 transcription; thus BIRC3 silencing prevents NPD1 induction of survival against oxidative stress.^[74]
• In 2016 Bazan and his colleagues showed in "in vivo" rodent models of limbic epileptogenesis (LE) that the phospholipid mediator platelet-activating factor (PAF) increases in LE and that PAF receptor (PAF-r) ablation mitigates its progression, suggesting that over-activation of PAF-r signaling induces aberrant neuronal plasticity in LE and leads to chronic dysfunctional neuronal circuitry that mediates epilepsy.^[75]

Translational medicine and industry

Start-Up Companies

• InSite Vision (Alameda, California): Scientific Co-Founder, 1987
• St. Charles Pharmaceuticals (New Orleans, Louisiana): Scientific Founder, 1997

Patents

• United States Patent No. P9501549; Inventors: Nicolas G. Bazan and Julio Alvarez-Builla Gomez and Assignee: Spain, "Nuevos derivados de N-acil-4-hidroxifenilamina con propiedades analgésicas y formulaciones farmaceuticas que los contienen." 1995
• United States Patent No. 5,554,636; Inventors: Nicolas G. Bazan and Julio Alvarez-Builla Gomez and Assignee: LSUMC, "N-acylated 4-hydroxyphenylamine derivatives with analgesic properties and pharmaceutical compositions containing them" and corresponding International Application No. PCT/US96/05456, published as International Publication No.WO 96/32940; Canadian application no. 2,218664, European application no.96915332.9, and Japanese application no. B-531944. 1996
• United States Patent No. 5,621,110; Inventors: Nicolas G. Bazan and Julio Alvarez-Builla Gomez and Assignee: LSUMC, "Process for preparing N-acylated 4-hydroxyphenylamine derivatives with analgesic properties." 1997
• United States Patent Filed "02/25/2002: Inventors: Jay Hunt, Haydee Bazan, Victor Marcheselli, Julio Alvarez-Builla Gomez, Nicolas G. Bazan and Assignee: LSUHSC, "Platelet-activating factor antagonist inhibition of angiogenesis and tumor growth induced by basic fibroblast growth factor." 2002
• United States Patent No. 6,653.311; Inventors: Nicolas G. Bazan, Carlos Sunkel, Julio Alvarez-Builla Gomez and Assignee: LSUHSC, "5-Lipoxygenase inhibitors: (2-azinylamino) quinone Derivatives." 2003
• United States Patent No. 6,566,359; Inventors: Nicolas G. Bazan, Carlos Sunkel, Victor Marcheselli and Julio Alvarez-Builla Gomez and Assignee: LSUHSC, "2,4,6-Trimethyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid esters as neuroprotective drugs." LAU-0901. 2003
• United States Patent Application Serial No. 10/459,911: Inventors: Nicolas G. Bazan, Carlos Sunkel, Dennis Paul, Julio Alvarez-Builla and Assignee: LSUHSC, "Synergistic combinations including N-acylated 4-hydroxyphenylamine derivatives with caffeine." 2003
• United States Patent Application Serial No. 60/589,445: Inventors: Nicolas G. Bazan, Walter J. Lukiw, Charles N. Serhan*, and Assignee: LSUHSC, "Neuroprotective and anti-inflammatory bioactive docosaehexanoic acid mediators in Alzheimer' disease." 2004
• United States Patent Application Serial No. 10/911,835: Inventors: Nicolas G. Bazan, Charles N. Serhan, Victor L. Marcheselli, Pranab K. Mukherjee, Sebastian G. Barreiro, Walter J. Lukiw, Song Hong, Karsten Gronert, and Albert E. Musto and Assignee: LSUHSC, "Neuroprotectin D1 protects against cellular apoptosis, stroke damage, Alzheimer's disease and retinal diseases." 2004
• United States Patent Filed pending: Inventors: Salomon Esquenazi, Haydee E.P. Bazan, Nicolas G. Bazan and Assignee: LSUHSC, "Topical treatment with nerve growth factor and docosahexaenoic acid in corneal refractive surgery." 2004
• United States Patent No. 6,806,291; Inventors: Nicolas G. Bazan, Carlos Sunkel, Anthony Vaccarino, Julio Alvarez-Builla, and Assignee: LSUHSC, "Analgesic compounds, their synthesis and pharmaceutical compositions containing them"; and corresponding U.S. Patent Application Serial No. 10/682,744, filed October 9, 2003; and corresponding International Application No. PCT/US2004/033609, filed October 12, 2004.
• United States Patent Application Serial No. 10/292,105; Inventors: Nicolas G. Bazan, Carlos Sunkel, Dennis Paul, Julio Alvarez-Builla Gomez and Assignee: LSUHSC, "Synergistic combinations including N-acylated 4-hydroxyphenylamine derivates with caffeine"; published as U.S. Patent Application Publication No. 2004/0092541; and corresponding, International Application No. PCT/US2003/036039, filed November 12, 2003, and published as International Publication No. WO 2004/043460. 2004

Other activities

• In 2005, Bazan launched his family wine label, "Nicolas Bazan Wines." The project is a collaborative effort between Bazan and Mark Wahle. Wahle is a medical doctor with a degree in enology from University of California at Davis. Wahle established the Wahle Family vineyards in Yamhill, Oregon. The Bazan block comprises 20 acres of the Holmes Hill vineyard site in Eola Hills, Oregon. Grapes for the Nicolas Bazan Wines are derived mainly from this block.^[76]
• In 2009, Bazan published the novel Una Vida: A Fable of Music and the Mind, which follows the neuroscientist Alvaro Cruz as he attempts to uncover the mysterious past of a New Orleans street singer known as Una Vida. Stricken with Alzheimer's, she can only offer clues about her past through her singing. As Cruz searches for Una Vida's true identity, he learns about the human psyche, the nature of memory, and himself. This book was adapted into the 2014 film Of Mind and Music.^[77]

External links

• LSU Health Sciences Center Neuroscience Center of Excellence
• Neuroscience Center of Excellence Faculty: Nicolas G. Bazan
• "Una Vida: A Fable of Music and the Mind"
• Una Vida motion picture adaptation
• Nicolas Bazan Wines

Notes and References

1. Bazan NG. Effects of ischemia and electroconvulsive shock on free fatty acid pool in the brain. Biochim Biophys Acta 218:1-10, 1970
2. Bazan NG: Changes in free fatty acids of brain by drug induced convulsions, electroshock and anesthesia. J Neurochem 18:1379-1385, 1971
3. Horrocks LA, Farooqui AA. NMDA receptor-stimulated release of arachidonic acid: Mechanisms for the Bazan Effect. In Cell Signal Transduction, Second Messengers, and Protein Phosphorylation in Health and Disease, AM Municio, MT Miras-Portugal (eds), Plenum Press, New York, pgs 113-128, 1994
4. Sun GY, Xu J, Jensen MD, Simonyi A: Phospholipase A2 in central nervous system: Implications for neurodegeneration diseases. J Lipid Res 45:205-213, 2004
5. Aveldano MI, Bazan NG. High content of docosahexaenoate and of total diacylglycerol in retina. Biochem Biophys Res Comm 48:689-693, 1972.
6. Aveldano MI, Bazan NG. Fatty acid composition and level of diacylglycerols and phosphoglycerides in brain and retina. Biochim Biophys Aca 296:1-9, 1973
7. Aveldano de Caldironi MI, Bazan NG: Composition and biosynthesis of molecular species of retina phosphoglycerides. Neurochem Internat 1:381-392, 1980
8. Aveldano MI, Bazan NG: Molecular species of phosphatidylcholine, ethanolamine, serine and inositol in microsomal and photoreceptor membranes of bovine retina. J Lipid Res 24:620-627, 1983
9. Aveldano MI, Pasquare de Garcia SJ, Bazan NG: Biosynthesis of molecular species of inositol, choline, serine, and ethanolamine glycerophospholipids in the bovine retina. J Lipid Res 24:628-638, 1983
10. Aveldano MI, Bazan NG: Differential lipid deacylation during brain ischemia in a homeotherm and a poikilotherm. Content and composition of free fatty acids and triacylglycerols. Brain Res 100:99-110, 1975
11. Aveldano MI, Bazan NG: Rapid production of diacylglycerols enriched in arachidonate and stearate during early brain ischemia. J Neurochem 25:919-920, 1975
12. Aveldano de Caldironi MI, Bazan NG. Acyl groups, molecular species and labeling by 14C-glycerol and 3H-arachidonic acid of vertebrate retina glycerolipids. In Advances in Experimental Medicine and Biology, Fucntino and Biosynthesis of Lipids, Vol 83, NG Bazan, RR Brenner, NM Giusto (esd), Plenum Press, New York, pgs 397-404, 1997.
13. Rodriguez de Turco EB, Morelli de Liberti S, Bazan NG: Stimulation of free fatty acid and diacylglycerol accumulation in cerebrum and cerebellum during bicuculline induced status epilepticus. Effect of pretreatment with alpha methyl p tyrosine and p chlorophenyl¬alamine. J Neurochem 40:252-259, 1983
14. Van Rooijen LAA, Vadnal R, Dobard P, Bazan NG: Enhanced inositide turnover in brain during bicuculline induced status epilepticus. Biochim Biophys Res Comm 136:827-834, 1986
15. Vadnal RE, Bazan NG: Electroconvulsive shock stimulates polyphosphoinositide degradation and inositol trisphosphate accumulation in rat cerebrum: Lithium pretreatment does not potentiate these changes. Neurosci Lett 80:75-79, 1987
16. Reddy TS, Bazan NG: Arachidonic acid, stearic acid and diacylglycerol accumulation correlates with the loss of phosphatidylinositol 4,5 bisphosphate in cerebrum 2 seconds after electroconvulsive shock. Complete reversion of changes 5 minutes after stimulation. J Neurosci Res 18:449-455, 1987
17. Vadnal RE, Bazan NG: Carbamazepine inhibits the electroconvulsive shock induced [H] IP3 accumulation in rat cerebral cortex and hippocampus. Biochem Biophys Res Comm 153:128-134, 1988
18. Katsura K, Rodriguez de Turco EB, Folbergrová J, Bazan NG, Siesjö: The coupling among energy failure, loss of ion homeostasis, and lipolysis during ischemia. J Neurochem 61:1677-1684, 1993
19. Bazan NG, Allan G, Rodriguez de Turco EB: Role of phospholipase A2 and membrane-derived lipid second messengers in excitable membrane function and transcriptional activation of genes. Implications in cerebral ischemia. Prog in Brain Res 96:247-257, 1993
20. Giusto NM, Bazan NG: Phosphatidic acid of retinal microsomes contains a high proportion of docosahexaenoate. Biochem Biophys Res Comm 91:791-794, 1979
21. Bazan NG, di Fazio de Escalante MS, Careaga MM, Bazan HEP, Giusto NM: High content of 22:6 (docosahexaenoate) and active [2-3H]glycerol metabolism of phosphatidic acid from photoreceptor membranes. Biochim Biophys Acta 712:702-706, 1982
22. Bazan HEP, Careaga MM, Sprecher H, Bazan NG: Chain elongation and desaturation of eicosapentaenoate to docosahexaenoate and phospholipid labeling in the rat retina in vivo. Biochim Biophys Acta 712:123-128, 1982
23. Bazan HEP, Sprecher H, Bazan NG: De novo biosynthesis of docosahexaenoyl phosphatidic acid in bovine retinal microsomes. Biochim Biophys Acta 796:11-19, 1984
24. Reddy TS, Bazan NG: Kinetic properties of arachidonoyl coenzyme A synthetase in rat brain microsomes. Arch Biochem Biophys 226:125-133, 1983
25. Reddy TS, Sprecher H, Bazan NG: Long chain acyl coenzyme A synthetase from rat brain microsomes: Kinetic studies using [1-14C]docosahexaenoic acid substrate. Eur J Biochem 145:21-29, 1984
26. Birkle DL, Bazan NG: Lipoxygenase and cyclooxygenase reaction products and incorporation into glycerolipids of radiolabeled arachidonic acid in the bovine retina. Prostaglandins 27:203-216, 1984
27. Birkle DL, Bazan NG: Effects of K+ depolarization on the synthesis of prostaglandins and hydroxyeicosatetra(5,8,11,14)enoic acids (HETE) in the rat retina. Evidence for esterification of 12 HETE in lipids. Biochim Biophys Acta 795:564-573, 1984
28. Bazan NG, Birkle DL, Reddy TS: Docosahexaenoic acid (22:6, n 3) is metabolized to lipoxygenase reaction products in the retina. Biochem Biophys Res Comm 125:741-747, 1984
29. Beuckmann CT, Gordon WC, Kanaoka Y, Eguchi N, Marcheselli VL, Gerashchenko DY, Urade Y, Hayaishi O, Bazan NG: Lipocalin-type prostaglandin D synthase (β-trace) is located in pigment epithelial cells of rat retina and accumulates within interphotoreceptor matrix. J Neurosci 16:6119-6124, 1996
30. Bazan NG, Reddy TS, Redmond TM, Wiggert B, Chader GJ: Endogenous fatty acids are covalently and non covalently bound to interphotoreceptor retinoid binding protein in the monkey retina. J Biol Chem 260:13677-13680, 1985
31. Scott BL, Reddy TS, Bazan NG: Docosahexaenoate metabolism and fatty acid composition in developing retinas of normal and rd mutant mice. Exp Eye Res 44:101-113, 1987
32. Scott BL, Racz E, Lolley RN, Bazan NG: Developing rod photoreceptors from normal and mutant rd mouse retinas: Altered fatty acid composition early in development of the mutant. J Neurosci Res 20:202 211, 1988
33. Scott BL, Bazan NG: Membrane docosahexanoate is supplied to the developing brain and retina by the liver. Proc Natl Acad Sci USA 86:2903 2907, 1989
34. Gordon WC, Bazan NG: Docosahexaenoic acid utilization during rod photoreceptor cell renewal. J Neurosci 10:2190-2204, 1990
35. Rodriguez de Turco, EB, Gordon WC, Bazan NG: Rapid and selective uptake, metabolism, and cellular distribution of docosahexaenoic acid among rod and cone photoreceptor cells in the frog retina. J Neurosci 11:3667-3678, 1991
36. Martin RE, Bazan NG: Changing fatty acid content of growth cone lipids prior to synaptogensis. J. Neurochem 59:318-325, 1992
37. Gordon WC, Rodriguez de Turco EB, Bazan NG:Retinal pigment epithelial cells play a central role in the conservation of docosahexaenoic acid by photoreceptor cells after shedding and phagocytosis. Curr Eye Res 11:73-83, 1992
38. Gordon WC, Bazan NG: Visualization of [3H]docosahexaenoic acid trafficking through photoreceptors and retinal pigment epithelium by electron microscope autoradiography. Invest Ophthalmol Vis Sci 34:2402-2411, 1993
39. Bazan NG, Rodriguez de Turco EB, Gordon WC: Pathways for the uptake and conservation of docosahexaenoic acid in photoreceptors and synapses: Biochemical and autoradiographic analysis. Can J Physiol Pharmacol 71(9):690-698, 1993
40. Bazan NG, Scott BL, Reddy TS, Pelias MZ: Decreased content of docosahexanoate and arachidonate in plasma phospholipids in Usher's syndrome. Biochem Biophys Res Commun 141:600-604, 1986
41. Ershov AV, Lukiw WJ, Bazan NG: Selective transcription factor induction in retinal pigment epithelial cells during photoreceptor phagocytosis. J Biol Chem 271:28458-28462, 1996
42. Gerashchenko DY, Beuckmann CT, Marcheselli VL, Gordon WC, Kanaoka Y, Eguchi N, Urade Y, Hayaishi O, Bazan NG: Localization of lipocalin-type prostaglandin D synthase (β-trace) in iris, ciliary body, and eye fluids. Invest Ophthalmol Vis Sci 39:198-203, 1998
43. Rodriguez de Turco EB, Deretic D, Bazan NG, Papermaster D: Post-golgi vesicles cotransport docosahexaenoyl-phospholipids and rhodopsin during frog photoreceptor membrane biogenesis. J Biol Chem 272:10491-10497, 1997
44. Panetta T, Marcheselli VL, Braquet P, Spinnewyn B, Bazan NG: Effects of a platelet-activating factor antagonist (BN 52021) on free fatty acids, diacylglycerols, polyphospho¬inositides and blood now in the gerbil brain: Inhibition of ischemia re¬perfusion induced cerebral injury. Biochem Biophys Res Comm 149:580-587, 1987
45. Marcheselli VL, Rossowska M, Domingo MT, Braquet P, Bazan NG: Distinct platelet-activating factor binding sites in synaptic endings and in intracellular membranes of rat cerebral cortex. J Biol Chem 265:9140-9145, 1990
46. Squinto SP, Block AL, Braquet P, Bazan NG: Platelet-activating factor stimulates a Fos/Jun/AP-1 transcriptional signaling system in human neuroblastoma cells. J Neurosci Res 24:558-566, 1989
47. Squinto SP, Braquet P, Block AL, Bazan NG: Platelet-activating factor activates HIV promoter in transfected SH-SY5Y neuroblastoma cells and MOLT-4 T lymphocytes. J Mol Neurosci 2:79-84, 1990
48. Bazan NG, Squinto SP, Braquet P, Panetta T, Marcheselli VL: Platelet-activating factor and polyunsaturated fatty acids in cerebral ischemia or convulsions: Intracellular PAF-binding sites and activation of a Fos/Jun/Ap-1 transcriptional signaling system. Lipids 26:1236-1242, 1991
49. Marcheselli VL, and Bazan NG: Platelet-activating factor is a messenger in the electroconvulsive shock-induced transcriptional activation of c-fos and zif-268 in hippocampus. J Neurosci Res 37:54-61, 1994
50. Clark GD, Happel LT, Zorumski CF, Bazan NG: Enhancement of hippocampal excitatory synaptic transmission by platelet-activating factor. Neuron 9:1211-1216, 1992
51. Kato K, Clark GD, Bazan NG, Zorumski CF: Platelet activating factor as a potential retrograde messenger in Ca1 hippocampal long-term potentiation. Nature 367:175-179, 1994
52. Izquierdo I, Fin C, Schmitz PK, Da Silva RC, Jerusalinsky D, Quillfeldt JA, Ferreira MBG, Medina JH, Bazan NG: Memory enhancement by intrahippocampal, intraamygdala, or intraentorhinal infusion of platelet-activating factor measured in an inhibitory avoidance task. Proc Natl Acad Sci 92:5047-5051, 1995
53. Packard MG, Teather L, Bazan NG: Effect of intra-caudate nucleus injections of platelet-activating factor and the PAF antagonist BN 52021 on memory. Neurobiol Learn Mem 66:177-182, 1996
54. Bazan NG, Fletcher BS, Herschman HR, Mukherjee PK: Platelet-activating factor and retinoic acid synergistically activate the inducible prostaglandin synthase gene. Proc Natl Acad Sci 91:5252-5256, 1994
55. Marcheselli VL, Bazan NG: Sustained induction of prostaglandin endoperoxide synthase-2 by seizures in hippocampus: Inhibition by a platelet-activating factor antagonist. J Biol Chem 271:24794-24799, 1996
56. Kolko M, DeCoster MA, Rodriguez de Turco EB, Bazan NG: Synergy by secretory phospholipase A2 and glutamate on inducing cell death and sustained arachidonic acid metabolic changes in primary cortical neuronal cultures. J Biol Chem 271:32722-32728, 1996
57. Kolko M, Bruhn T, Christensen T, Lazdunski M, Lambeau G, Bazan NG, Diemer NH: Secretory phospholipase A2 potentiates glutamate-induced rat striatal neuronal cell death in vivo. Neurosci Letters 274:167-170, 1999
58. Rodriguez de Turco EB, Jackson FR, DeCoster MA, Kolko M, Bazan NG: Glutamate signaling and secretory phospholipase A2 modulate the release of arachidonic acid from neuronal membrane. J Neurosi Res 68:558-567, 2002
59. Rodriguez de Turco EB, Tang W, Tophan MK, Sakane F, Marcheselli VL, Chen C, Taketomi A, Prescott SM, Bazan NG: Diacylglycerol kinase ε regulates seizure susceptibility and long-term potentiation through arachidonoyl-inositol lipid signaling. Pro Natl Acad Sci 98:4740-4745, 2001
60. Gordon WC, Casey DM, Lukiw WJ, Bazan NG: DNA damage and repair in light-induced photoreceptor degeneration. Invest Ophthalmol Vis Sci 43:3511-3521, 2002
61. Lukiw WJ, Gordon WC, Rogaev EI, Thompson H, Bazan NG: Presenilin-2 (PS2) expression up-regulation in a model of retinopathy of prematurity and pathoangiogensis. NeuroReport 12:53-57, 2001
62. Bazan NG, Birkle DL, Reddy TS: Docosahexaenoic acid (22:6, n 3) is metabolized to lipoxygenase reaction products in the retina. Biochem Biophys Res Commun 125:741-747, 1984
63. Marcheselli VL, Hong S, Lukiw WJ, Tian XH, Gronert K, Musto A, Hardy M, Gimenez JM, Chiang N, Serhan CN, Bazan NG: Novel docosanoids inhibit brain ischema-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression. J Biol Chem 278:43807-43817, 2003
64. Belayev L, Marcheselli VL, Khoutorova L, Rodriguez de Turco EB, Busto R, Ginsberg MD, Bazan NG: Docosahexaenoic acid complexed to albumin elicits high-grade ischemic neuroprotection. Stroke 36:118-23, 2004
65. Mukherjee PK, Marcheselli VL, Serhan CN, Bazan NG: Neuroprotectin D1: A docosahexanoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress. Proc Natl Acad Sci, USA 101:8491-8496, 2004
66. Lukiw WJ, Cui JG, Marcheselli VL, Bodker M, Botkjaer A, Gotlinger K, Serhan CN, Bazan NG: A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease. J Clin Invest 115:2774-2783, 2005
67. Mukherjee PK, Marcheselli VL, Barreiro S, Hu J, Bok D, Bazan NG: Neurotrophins enhance retinal pigment epithelial cell survival through neuroprotectin D1 signaling. Proc Natl Acad Sci USA 104:13152-13157, 2007
68. Mukherjee PK, Marcheselli VL, de Rivero Vaccari JC, Gordon WC, Jackson F, Bazan NG: Photoreceptor outer segment phagocytosis attenuates oxidative stress-induced apoptosis with concomitant neuroprotectin D1 synthesis. Proc Natl Acad Sci USA 104:13158-13163, 2007
69. Bazan NG: Homeostatic regulation of photoreceptor cell integrity: significance of the potent mediator neuroprotectin D1 biosynthesized from docosahexaenoic acid: the Proctor Lecture. Invest Ophthalmol Vis Sci. 48:4866-4881, 2007
70. Musto AE, Gjorstrup P, Bazan NG: The omega-3 fatty acid-derived neuroprotectin D1 limits hippocampal hyperexcitability and seizure susceptibility in kindling epileptogenesis. Epilepsia 52(9):1601-8, 2011
71. Web site: Retina protein that may help conquer blindness discovered.
72. Rice DS, Calandria JM, Gordon WC, Jun B, Zhou Y, Gelfman CM, Li S, Jin M, Knott EJ, Chang B, Abuin A, Issa T, Potter D, Platt KA, Bazan NG: Adiponectin receptor 1 conserves docosahexaenoic acid and promotes photoreceptor cell survival. Nat Commun. 2015;6:6228
73. Web site: LSU Health New Orleans Makes Discovery Key to Preventing Blindness and Stroke Devastation .
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