2. eNOS targeting and translocation
3. Sphingosine 1-phosphate and eNOS
4. RNA interference and endothelial signaling
6. Protein kinases and phosphoprotein phosphatases in endothelial signaling
7. eNOS acylation and protein interactions
11. Book chapters
Hess CN, Kou R, Johnson R, Li GK and Michel T. ADP signaling in vascular endothelial cells: ADP-dependent eNOS activation requires the expression but not the kinase activity of AMP-activated protein kinase. J Biol Chem 2009, 284:32209-32224. PMCID Journal: in process PDF
Jin, B., Sartoretto, J., Gladyshev, V., and Michel T. Endothelial nitric oxide synthase negatively regulates hydrogen peroxide-stimulated AMP-activated protein kinase in endothelial cells. PNAS 106: 17343-17348, 2009. PDF
Kou R, Sartoretto J and Michel T. Regulation of Rac1 by simvistatin in endothelial cells: differential roles of AMP-activated protein kinase and calmodulin-dependent kinase kinase-ß. J Biol Chem 2009, 14734-14743. PDF
Sartoretto JL, Jin BY, Bauer M, Gertler FB, Liao R, and Michel T. Regulation of VASP phosphorylation in cardiac myocytes: differential regulation by cyclic nucleotides and modulation of protein expression in diabetic and hypertrophic heart. 2009 Am J Physiol Heart Circ Physiol 297:1697-1710, 2009. First published Sep 4, 2009; doi:10.1152/ajpheart.00595.PDF
Sugiyama T and Michel T. Thiol-metabolizing proteins and endothelial redox state: Differential modulation of eNOS and biopterin pathways. 2010 Am J Physiol Heart Circ Phys 298:H194-H201. PDF
Selected review articles
Nitric oxide, the active ingredient in important cardiovascular drugs such as nitroglycerin, is synthesized by a family of nitric oxide synthases. In the early 1990’s, more than a century after the first use of nitroglycerin for treatment of angina pectoris, molecular clones for nitric oxide synthases were isolated and characterized. Much has been learned in recent years about the regulation of this important family of proteins, their physiological roles, and their dysregulation in important cardiovascular disease states such as diabetes and hypercholesterolemia. These review articles span a decade of work by my lab and by many others in this active area of investigation.
Igarashi J, Michel T. Editorial: Endothelial cell-derived S1P. Circulation Research. 2008;102:630-632. PDF
Lamas S, Lowenstein C, Michel T. Nitric oxide signaling comes of age: 20 years and thriving. Cardio Research. 2007; 75:207-209. PDF
Dudzinski D, Michel T. Life history of eNOS: Partners and Pathways. Cardio Research. 2007; 75: 247-260. PDF
Dudzinski D, Igarashi J, Greif D, Michel T. Pharmacology and molecular regulation of nitric oxide synthases. Annu Rev Pharmacol Toxicol. 2006;46:235-76. PDF
Lowenstein C, Michel T. What's in a name? eNOS and anaphylactic shock. J Clin Invest. 2006; 116: 2075-78. PDF
Igarashi J, Michel T. More sweetness than light? A search for the causes of diabetic vasculopathy. J Clin Invest. 2001;108(10):1425-7. PDF
Michel T, Feron O. Nitric oxide synthases: which, where, how, and why? J Clin Invest. 1997;100 (9):2146-52. PDF
Michel T. The guide to politically correct cardiology. J Irreprod Results. 1993;38:7-8. PDF
eNOS targeting and translocation
Several years ago, we discovered that eNOS is targeted to specialized signal-transducing membrane microdomains termed plasmalemmal caveolae. Post-translational modifications of eNOS play a key role in the reversible agonist-modulated translocation of the enzyme. The papers listed below describe our work on the key molecular determinants involved in eNOS targeting and translocation.
Erwin PA, Mitchell D, Marletta M, Michel T. Subcellular targeting and S-nitrosylation of endothelial nitric oxide synthase. J Biol Chem. 2006;281:151-7. PDF
Gonzalez E, Kou R, Michel T. Rac1 and modulation of P13-kinase pathways in vascular endothelial cells. J Biol Chem. 2006;281:3210-6. PDF
Gonzalez E, Nagiel A, Lin A, Golan DE, Michel T. siRNA-mediated downregulation of caveolin-1 differentially modulates signaling pathways in endothelial cells. J Biol Chem. 2004;279:20659-69. PDF
Jobin CM, Chen H, Lin AJ, Yacono PW, Igarashi J, Michel T, Golan DE. Receptor-regulated dynamic interaction between endothelial nitric oxide synthase and calmodulin revealed by fluorescence resonance energy transfer in living cells. Biochemistry. 2003;42:11716-25. PDF
Gonzalez E, Kou R, Lin AJ, Golan DE, Michel T. Subcellular targeting and agonist- induced sitespecific phosphorylation of endothelial nitric oxide synthase. J Biol Chem. 2002;277:39554-60. PDF
Igarashi J, Michel T. Agonist-modulated targeting of the EDG-1 receptor to plasmalemmal caveolae: eNOS activation by sphingosine 1-phosphate and the role of caveolin-1 in sphingolipid signal transduction. J Biol Chem. 2000;275(32):363-70. PDF
Prabhakar P, Cheng V, Michel T. A chimeric transmembrane domain directs endothelial nitric oxide synthase palmitoylation and targeting to plasmalemmal caveolae. J Biol Chem. 2000;275:19416-21. PDF
Goetz R, Thatte H, Prabhakar P, Cho M, Michel T, Golan D. Estradiol induces the calcium dependent translocation of endothelial nitric oxide synthase. Proc Natl Acad Sci USA. 1999;96:2788-93. PDF
Prabhakar P, Thatte H, Goetz R, Cho M, Golan D, Michel T. Receptor-mediated redistribution of endothelial nitric oxide synthase. J Biol Chem. 1998;273:27389-93. PDF
Feron O, Belhassen L, Kobzik L, Smith TW, Kelly RA, Michel T. Endothelial nitric oxide synthase targeting to caveolae: specific interactions with caveolin isoforms in cardiac myocytes and endothelial cells. J Biol Chem. 1996;271:22810-4. PDF
Shaul P, Smart E, Robinson LJ, German Z, Ying Y, Anderson RGW, Michel T. Acylation targets endothelial nitric oxide synthase to plasmalemmal caveolae. J Biol Chem. 1996;271:6518-23. PDF
Robinson LJ, Michel T. Mutagenesis of palmitoylation sites in endothelial nitric oxide synthase identifies a novel motif for dual acylation and subcellular targeting. Proc Natl Acad Sci USA. 1995;92:11776-80. PDF
Busconi L, Michel T. Endothelial nitric oxide synthase membrane targeting: evidence against involvement of a specific myristate receptor. J Biol Chem. 1994;269:25016-20. PDF
Michel T, Li GK, Busconi L. Phosphorylation and subcellular translocation of endothelial nitric oxide synthase. Proc Natl Acad Sci USA. 1993;90:6252-6. PDF
Sphingosine 1-phosphate and eNOS
Sphingosine 1-phosphate (S1P) is a platelet-derived sphingolipid that Junsuke Igarashi (now at Kagawa University) discovered to play a major role in eNOS regulation via activation of G protein-coupled S1P (EDG) receptors in the vascular endothelium. We have characterized many aspects of S1P-modulated pathways in control of NO-dependent signaling; please see the papers listed below.
Igarashi J, Michel T. Editorial: Endothelial cell-derived S1P. Circulation Research. 2008;102:630-632. PDF
Levine YC, Li GK, Michel T. Agonist-modulated regulation of AMP-activated protein kinase in endothelial cells: Evidence for an AMPK RAC1 AKT eNOS pathway. J Biol Chem. 2007; 282:20351-20364. PDF
Gonzalez E, Kou R, Michel T. Rac1 and modulation of P13-kinase pathways in vascular endothelial cells. J Biol Chem. 2006;281:3210-6. PDF
Gonzalez E, Nagiel A, Lin A, Golan DE, Michel T. siRNA-mediated downregulation of caveolin-1 differentially modulates signaling pathways in endothelial cells. J Biol Chem. 2004;279:20659-69. PDF
Igarashi J, Erwin P, Dantas AP, Chen H, Michel T. VEGF induces S1P1 receptors in endothelial cells: implications for cross-talk between sphingolipid and growth factor receptors. Proc Natl Acad Sci USA. 2003;100:10664-9. PDF
Dantas AP, Igarashi J, Michel T. Sphingosine 1-phosphate and control of vascular tone. Am J Physiol Heart Circ Physiol. 2003;284:H2045-52. PDF
Kou R, Igarashi J, Michel T. Lysophosphatidic acid and receptor-mediated regulation of endothelial nitric oxide synthase. Biochemistry. 2002;41:4982-8. PDF
Igarashi J, Michel T. Sphingosine 1-phosphate modulates isoform-specific activation of phosphoinositide 3-kinase beta in vascular endothelial cells implications for eNOS regulation by G-protein coupled receptors. J Biol Chem. 2001;276:36281-8. PDF
Igarashi J, Bernier SG, Michel T. Sphingosine 1-phosphate and activation of endothelial nitric oxide synthase: differential regulation of Akt and MAP kinase pathways by EDG and bradykinin receptors. J Biol Chem. 2001;276:12420-6. PDF
Igarashi J, Michel T. Agonist-modulated targeting of the EDG-1 receptor to plasmalemmal caveolae: eNOS activation by sphingosine 1-phosphate and the role of caveolin-1 in sphingolipid signal transduction. J Biol Chem. 2000;275(32):363-70. PDF
Igarashi J, Thatte H, Prabhakar P, Golan DE, Michel T. Calcium-independent activation of endothelial nitric oxide synthase by ceramide. Proc Natl Acad Sci USA. 1999;96:12583-8. PDF
RNA interference and endothelial signaling
The 2006 Nobel Prize in Physiology or Medicine was awarded to Fire and Mello for their pathbreaking work on genetic regulation by small interfering RNAs (siRNA). We have been exploiting duplex siRNA constructs to “knockdown” a broad range of signaling proteins in cultured endothelial cells. These studies have provided interesting new insights into signal transduction pathways in the endothelium, and have revealed novel features of eNOS regulation involving caveolae and the cytoskeleton. The figure shown above is from Gonzalez et al 2006 (PDF)
Sugiyama T, Levy B and Michel T. Tetrahydrobiopterin recycling: a key determinant of eNOSdependent signaling pathways in vascular endothelium. J Biol Chem 2009, 12691-12700.PDF
Chen H, Levine YC, Golan D, Michel T, Lin A. ANP-initiated cGMP pathways regulate VASP phosphorylation and angiogenesis in vascular endothelium. J Biol Chem. 2007; PDF
Levine YC, Li GK, Michel T. Agonist-modulated regulation of AMP-activated protein kinase in endothelial cells: Evidence for an AMPK RAC1 AKT eNOS pathway. J Biol Chem. 2007; 282:20351-20364. PDF
Gonzalez E, Kou R, Michel T. Rac1 and modulation of P13-kinase pathways in vascular endothelial cells. J Biol Chem. 2006;281:3210-6. PDF
Chen HJ, Michel T. Insulin signaling in vascular endothelial cells: a key role for heterotrimeric G proteins revealed by siRNA-mediated G beta-1 knockdown. Biochemistry. 2006;45:8023-33. PDF
Kou R, SenBannerjee S, Jain M, Michel T. Differential regulation of vascular endothelial growth factor receptors revealed by RNA interference: interactions of VEGFR-1 and VEGFR-2 in endothelial cell signaling. Biochemistry. 2005;44:15064-73. PDF
Gonzalez E, Nagiel A, Lin A, Golan DE, Michel T. siRNA-mediated downregulation of caveolin-1 differentially modulates signaling pathways in endothelial cells. J Biol Chem. 2004;279:20659-69. PDF
S-nitrosylation
Over the past several years, protein S-nitrosylation has been revealed to be a key pathway that regulates a broad range of proteins involved in cellular homeostasis. Studies by Phillip Erwin in my lab led to the discovery that eNOS itself undergoes reversible receptor-mediated S-nitrosylation at specific cysteine, and revealed the novel finding that eNOS subcellular localization is a key determinant of S-nitrosylation. This slide shows a figure from Phillip’s 2005 paper: eNOS in resting endothelial cells is S-nitrosylated, but is reversibly de-nitrosylated following addition of the eNOS agonist VEGF, associated with enzyme activation.
Erwin PA, Mitchell D, Marletta M, Michel T. Subcellular targeting and S-nitrosylation of endothelial nitric oxide synthase. J Biol Chem. 2006;281:151-7. PDF
Mitchell DA, Erwin PA, Michel T, Marletta MA. S-Nitrosation and regulation of inducible nitric oxide synthase. Biochemistry. 2005;44:4636-47. PDF
Erwin PA, Lin A, Golan DE, Michel T. Receptor-regulated dynamic S-nitrosylation of endothelial nitric oxide synthase in vascular endotheslial cells. J Biol Chem. 2005;280:19888-94. PDF
Stamler JA, Simon D, Jaraki O, Mullins M, Michel T, Singel D, Loscalzo J. S-nitrosylation of proteins by nitric oxide: formation of novel biologically active compounds. Proc Natl Acad Sci USA. 1992;89(1):444-8. PDF
Protein kinases and phosphoprotein phosphatases in endothelial signaling
All NOS isoforms are phosphoproteins, but eNOS is particularly endowed: work from many labs has revealed that there are at least six phosphorylation sites, some of which lead to enzyme activation, while others inhibit enzyme activity. Listed below are some of our papers on eNOS phosphorylation, dating back to our discovery in 1992 that eNOS is phosphorylated.
Jin, B., Sartoretto, J., Gladyshev, V., and Michel T. Endothelial nitric oxide synthase negatively regulates hydrogen peroxide-stimulated AMP-activated protein kinase in endothelial cells. PNAS 2009, in press.PDF
Kou R, Sartoretto J and Michel T. Regulation of Rac1 by simvistatin in endothelial cells: differential roles of AMP-activated protein kinase and calmodulin-dependent kinase kinase-ß. J Biol Chem 2009, 14734-14743. PDF
Sugiyama T, Levy B and Michel T. Tetrahydrobiopterin recycling: a key determinant of eNOSdependent signaling pathways in vascular endothelium. J Biol Chem 2009, 12691-12700.PDF
Chen H, Levine YC, Golan D, Michel T, Lin A. ANP-initiated cGMP pathways regulate VASP phosphorylation and angiogenesis in vascular endothelium. J Biol Chem. 2008;283:4439-4447. PDF
Kou R, Michel T. Epinephrine regulation of the endothelial isoform of nitric-oxide synthase: Roles of RAC1 and beta3-adrenergic receptors in endothelial NO signaling. J Biol Chem. 2007;282:32719-32729.PDF
Levine YC, Li GK, Michel T. Agonist-modulated regulation of AMP-activated protein kinase in endothelial cells: Evidence for an AMPK RAC1 AKT eNOS pathway. J Biol Chem. 2007; 282:20351-20364. PDF
Chen HJ, Michel T. Insulin signaling in vascular endothelial cells: a key role for heterotrimeric G proteins revealed by siRNA-mediated G beta-1 knockdown. Biochemistry. 2006;45:8023-33. PDF
Erwin PA, Mitchell D, Marletta M, Michel T. Subcellular targeting and S-nitrosylation of endothelial nitric oxide synthase. J Biol Chem. 2006;281:151-7. PDF
Gonzalez E, Kou R, Michel T. Rac1 and modulation of P13-kinase pathways in vascular endothelial cells. J Biol Chem. 2006;281:3210-6. PDF
Erwin PA, Lin A, Golan DE, Michel T. Receptor-regulated dynamic S-nitrosylation of endothelial nitric oxide synthase in vascular endotheslial cells. J Biol Chem. 2005;280:19888-94. PDF
Greif DE, Sacks DB, Michel T. Calmodulin phosphorylation and modulation of endothelial nitric oxide synthase catalysis. Proc Natl Acad Sci USA. 2004;10:1165-1170. PDF
Gonzalez E, Nagiel A, Lin A, Golan DE, Michel T. siRNA-mediated downregulation of caveolin-1 differentially modulates signaling pathways in endothelial cells. J Biol Chem. 2004;279:20659-69. PDF
Greif D, Kou R, Michel T. Site-specific dephosphorylation of endothelial nitric oxide synthase by protein phosphatase PP2A: evidence for crosstalk between phosphorylation sites. Biochemistry. 2002;41:15845-53. PDF
Gonzalez E, Kou R, Lin AJ, Golan DE, Michel T. Subcellular targeting and agonist- induced sitespecific phosphorylation of endothelial nitric oxide synthase. J Biol Chem. 2002;277:39554-60. PDF
Kou R, Greif D, Michel T. Dephosphorylation of endothelial nitric oxide synthase by vascular endothelial growth factor: implications for the vascular responses to cyclosporin. J Biol Chem. 2002;277:29669-73. PDF
Igarashi J, Bernier SG, Michel T. Sphingosine 1-phosphate and activation of endothelial nitric oxide synthase: differential regulation of Akt and MAP kinase pathways by EDG and bradykinin receptors. J Biol Chem. 2001;276:12420-6. PDF
Bernier SG, Haldar S, Michel T. Bradykinin-regulated interactions of the mitogen- activated protein kinase pathway with the endothelial nitric-oxide synthase. J Biol Chem. 2000;275:30707-15. PDF
Robinson LJ, Ghanouni P, Michel T. "Post-translational modifications of endothelial nitric oxide synthase." Methods in Enzymology. 1996;268:436-48. PDF
Michel T, Li GK, Busconi L. Phosphorylation and subcellular translocation of endothelial nitric oxide synthase. Proc Natl Acad Sci USA. 1993;90:6252-6. PDF
eNOS acylation and protein interactions
Like many signaling proteins targeted to plasmalemmal caveolae, eNOS undergoes acylation. Not long after we cloned eNOS, Liliana Busconi discovered that the enzyme is modified by co-translational N-myristoylation; she and Lisa Robinson then found that eNOS undergoes post-translational thiopalmitoylation. Receptor-modulated depalmitoylation of eNOS plays a role in enzyme translocation, and there is a close relationship between the enzyme’s subcellular localization and phosphorylation. This model slide depicts eNOS interacting with caveolin in a caveola, tethered by a molecule of myristate and two of palmitate. The enzyme is inactive until calcium-calmodulin displaces caveolin and binds to eNOS, thereby activating the enzyme.
Erwin PA, Mitchell D, Marletta M, Michel T. Subcellular targeting and S-nitrosylation of endothelial nitric oxide synthase. J Biol Chem. 2006;281:151-7. PDF
Gonzalez E, Nagiel A, Lin A, Golan DE, Michel T. siRNA-mediated downregulation of caveolin-1 differentially modulates signaling pathways in endothelial cells. J Biol Chem. 2004;279:20659-69. PDF
Gonzalez E, Kou R, Lin AJ, Golan DE, Michel T. Subcellular targeting and agonist- induced sitespecific phosphorylation of endothelial nitric oxide synthase. J Biol Chem. 2002;277:39554-60. PDF
Yeh DC, Duncan JA, Yamashita S, Michel T. Depalmitoylation of endothelial nitric oxide synthase by acyl-protein thioesterase 1 is potentiated by Ca(2+)-calmodulin. J Biol Chem. 1999;274(33):148-54. PDF
Feron O, Saldana F, Michel JB, Michel T. The endothelial nitric oxide synthase-caveolin regulatory cycle. J Biol Chem. 1998;273:3125-8. PDF
Feron O, Michel JB, Sase K, Michel T. Dynamic regulation of endothelial nitric oxide synthase: complementary roles of dual acylation and caveolin interactions. Biochemistry. 1998;37(1):193-200. PDF
Michel JB, Feron O, Prabhakar P, Sase K, Michel T. Caveolin versus calmodulin: counterbalancing allosteric regulators of endothelial nitric oxide synthase. J Biol Chem. 1997;272:25907-12. PDF
Michel JB, Feron O, Sacks D, Michel T. Reciprocal regulation of endothelial nitric synthase by caveolin and calmodulin. J Biol Chem. 1997;272:15583-6. PDF
Shaul P, Smart E, Robinson LJ, German Z, Ying Y, Anderson RGW, Michel T. Acylation targets endothelial nitric oxide synthase to plasmalemmal caveolae. J Biol Chem. 1996;271:6518-23. PDF
Robinson LJ, Ghanouni P, Michel T. "Post-translational modifications of endothelial nitric oxide synthase.". Methods in Enzymology. 1996;268:436-48. PDF
Robinson LJ, Michel T. Mutagenesis of palmitoylation sites in endothelial nitric oxide synthase identifies a novel motif for dual acylation and subcellular targeting. Proc Natl Acad Sci USA. 1995;92:11776-80. PDF
Lee CM, Robinson LJ, Michel T. Oligomerization of endothelial nitric oxide synthase: c0- immunoprecipitation of wild-type and mutant enzymes in transfected cells. J Biol Chem. 1995;270:27403-6. PDF
Robinson LJ, Busconi L, Michel T. Agonist-modulated palmitoylation of endothelial nitric oxide synthase. J Biol Chem. 1995;270:995-8. PDF
Busconi L, Michel T. Endothelial nitric oxide synthase membrane targeting: evidence against involvement of a specific myristate receptor. J Biol Chem. 1994;269:25016-20. PDF
Busconi L, Michel T. Endothelial nitric oxide synthase. N-terminal myristoylation determines subcellular localization. J Biol Chem. 1993;268:8410-3. PDF
eNOS in the heart
eNOS is expressed in multiple non-endothelial tissues, where the enzyme is involved in processes as diverse as neurotransmission and the modulation of cardiac myocyte function.
Feron O, Dessy C, Opel DJ, Arstall M, Kelly RA, Michel T. Modulation of the endothelial nitric oxide synthase-caveolin interaction in cardiac myocytes: implications for the autonomic regulation of heart rate. J Biol Chem. 1998;273:30249-54. PDF
Feron O, Smith TW, Michel T, Kelly RA. Dynamic targeting of the agonist- stimulated m2 muscarinic cholinergic acetylcholine receptor to caveolae in cardiac myocytes. J Biol Chem. 1997;272:17744-8. PDF
Feron O, Belhassen L, Kobzik L, Smith TW, Kelly RA, Michel T. Endothelial nitric oxide synthase targeting to caveolae: specific interactions with caveolin isoforms in cardiac myocytes and endothelial cells. J Biol Chem. 1996;271:22810-4. PDF
Balligand JL, Kobzik L, Han X, Kaye DM, Belhassen L, O'Hara DS, Kelly RA, Smith TW, Michel T. Nitric oxide-dependent parasympathetic signaling is due to activation of constitutive endothelial (type III) nitric oxide synthase in cardiac myocytes. J Biol Chem. 1995;270:14582-6. PDF
Balligand JL, Ungureanu-Longrois D, Simmons W, Kobzik L, Lamas S, Lowenstein C, Kelly RA, Smith TW, Michel T. Induction of NO synthase in rat cardiac microvascular endothelial cells by IL-1 beta and IFN-gamma. Am J Physiol. 1995;268:H1293-303. PDF
Balligand JL, Ungureaunu-Longrois D, Simmons W, Lowenstein C, Malinski T, Kelly RA, Smith TW, Michel T. Cytokine-inducible nitric oxide synthase (iNOS) expression in cardiac myocytes: characterization and regulation of iNOS expression and detection of iNOS activity in single cardiac myocytes in vitro. J Biol Chem. 1994;169:27580-8. PDF
Balligand JL, Kelly RA, Marsden P, Smith TW, Michel T. Control of cardiac muscle cell function by an endogenous nitric oxide signaling system. Proc Natl Acad Sci USA. 1993;90 (1):347-51. PDF
Cloning and purification
eNOS was first cloned from bovine aortic endothelial cells, which remain the archetype of cultured endothelial cell systems.
Greif D, Kou R, Michel T. Site-specific dephosphorylation of endothelial nitric oxide synthase by protein phosphatase PP2A: evidence for crosstalk between phosphorylation sites. Biochemistry. 2002;41:15845-53. PDF
Michel JB, Feron O, Sacks D, Michel T. Reciprocal regulation of endothelial nitric synthase by caveolin and calmodulin. J Biol Chem. 1997;272:15583-6. PDF
Michel T, Xie QW, Nathan C. Molecular biological analysis of nitric oxide synthases. In: Feelisch M and Stamler J (eds.) Methods in Nitric Oxide Research. Wiley;1996. p. 161-176.
Robinson LJ, Ghanouni P, Michel T. Post-translational modifications of endothelial nitric oxide synthase. Methods in Enzymology. 1996;268:436-48. PDF
Robinson LJ, Michel T. Expression of endothelial nitric oxide synthase expression in heterologous systems. Methods Enzymol. 1996;269:55-64. PDF
Busconi L, Michel T. Recombinant endothelial nitric oxide synthase: post-translational modifications in a baculovirus expression system. Mol Pharm. 1995;47:655-9. PDF
Robinson LJ, Weremowicz S, Morton CJ, Michel T. Isolation and chromosomal localization of the human endothelial nitric oxide synthase (NOS3) gene. Genomics. 1994;19:350-7. PDF
Marsden PA, Schappert KT, Chen HS, Flowers M, Sundell CL, Wilcox JN, Lamas S, Michel T. Molecular cloning and characterization of human endothelial nitric oxide synthase. FEBS Lett. 1992;307:287-93. PDF
Lamas S, Marsden PA, Li GK, Tempst P, Michel T. Endothelial nitric oxide synthase: molecular cloning and characterization of a distinct constitutive enzyme isoform. Proc Natl Acad Sci USA. 1992;89:6348-52. PDF
eNOS in firefly flashing
NO is a known insect neurotransmitter, and it took the efforts of a multidisciplinary research group- involving a firefly ecologist, insect neurophysiologist, mitochondrial expert, and NO biochemist- to sort out this novel and intriguing role of NO in the control of firefly flashing. This model for flash control is described in greater detail on the Tufts University website explaining this work.
Aprille JR, Lagace CJ, Lewis SM, Michel T, Modica-Napolitano JS, Trimmer BA, Zayas RM. Mechanism of firefly flash control: NO inhibition of oxygen consumption in lantern mitochondria is reversed by light. In: Stanley PE and Kricka LJ, eds. Bioluminescence & Chemiluminescence: Progress & Current Applications. Singapore: World Scientific Publishing;2002. p. 25-8.
Trimmer B, Aprille J, Dudzinski D, Lagace C, Lewis S, Michel T, Zayas R. Regulation of firefly flashing by nitric oxide. Science. 2001;292:2486-8. PDF
Book chapters
Dudzinski D and Michel T. Vascular biology of nitric oxide and NO synthases. In: Hemostasis and Thrombosis, 4th ed. L. Clowes, ed. Lippincott Williams and Wilkins, Philadelphia, 2006, pp. 653-667.
Michel T. Treatment of myocardial ischemia. In: Goodman and Gilman’s Pharmacological Basis of Therapeutics, 11th ed. L Brunton, editor. McGraw Hill, New York, 2005, pp 823-844.
Yeh DC and Michel T. Pharmacology of Vascular Tone. In: Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy, DE Golan et al, eds. Lippincott Williams and Wilkins, Baltimore, 2004, pp.317-334.
Aprille JR, Lagace CJ, Lewis SM, Michel T, Modica-Napolitano JS, Trimmer BA and Zayas RM. Mechanism of firefly flash control: NO inhibition of oxygen consumption in lantern mitochondria is reversed by light. In Bioluminescence & Chemiluminescence: Progress & Current Applications, pp 25-28, Editors: Stanley PE & Kricka LJ. World Scientific Publishing, Singapore 2002.
Feron O and Michel T. Cell and molecular biology of nitric oxide synthases. In: Nitric Oxide and the Cardiovascular System, J. Loscalzo and J. A. Vita, eds. Humana Press Inc., Totowa, NJ, 2000, pp. 11-32.
Sase K and Michel T. Regulatory mechanisms of endothelial nitric oxide synthase. In: Yasue H (ed) Coronary Artery Spasm. Axel Springer Japan, Tokyo 2000, pp. 19-25.
Downey W and Michel T. Molecular and cellular regulation of endothelial nitric oxide synthase. In: Goodman R and Panda J (eds). Endothelium, nitric oxide and atherosclerosis. Futura (NY), 1999, pp. 29-37.
Michel T and Weinfeld MS. Stable coronary artery disease: angina and atherosclerosis. In: Melmon KL et al (eds.) Melmon and Morelli’s Clinical Pharmacology: Basic Principles in Therapeutics, Fourth Edition, McGraw Hill, New York, 2000, pp. 114-131.
Michel T, Sase K and Lamas S. Molecular regulation of nitric oxide synthases. In: Marks A and Taubman M (eds.) Molecular Biology of Cardiovascular Disease. Marcel Dekker (NY), 1997, pp. 141-160.
Michel T and Lamas S. Endothelium-derived nitric oxide and the control of vascular tone. In: Jameson L (ed) Textbook of Molecular Medicine. Blackwell (Cambridge MA) 1999.
Lamas S and Michel T. Molecular biological features of the nitric oxide synthases. In: Zapol W (ed.) Nitric Oxide and the Lung, Marcel Dekker (NY), 1996, pp. 59-68.
Robinson LJ, Morton CC and Michel T. The constitutive endothelial NO synthase gene: implications for its evolution and cellular regulation. In: S. Moncada (ed.) The biology of nitric oxide, Portland Press (London), pp. 1-4.
Michel T, Xie QW, Nathan C. Molecular biological analysis of nitric oxide synthases. In: Feelisch M and Stamler J (eds.) Methods in Nitric Oxide Research, Wiley, 1996; pp. 161-176.
Michel T, Hoffman BB, Lefkowitz RJ. Regulation of adenylate cyclase by adrenergic receptors. In: Litwack G, ed. Biochemical Actions of Hormones, 1982, vol. IX, pp 43-68.
