Top

Published in:

2013 | OriginalPaper | Chapter

35. Redox Activity of Cell-Free Hemoglobin: Implications for Vascular Oxidative Stress and Endothelial Dysfunction

Author : Felice D’Agnillo

Published in: Hemoglobin-Based Oxygen Carriers as Red Cell Substitutes and Oxygen Therapeutics

Publisher: Springer Berlin Heidelberg

Activate our intelligent search to find suitable subject content or patents.

search-config

AI-assisted search

Off

Abstract

Cell-free hemoglobin (Hb) outside the natural protective environment of the red blood cell (RBC) can undergo uncontrolled redox transformations to non-functional and/or toxic protein-bound and unbound species. Understanding the impact of Hb redox activity on vascular endothelial integrity and function remains a critical factor in the development of safe and efficacious acellular Hb-based oxygen therapeutics. This chapter will provide an overview of Hb redox reactions and their propensity to generate oxidative stress in the vascular system. Specific emphasis will be placed on studies from our laboratory that link oxidative stress with the development of endothelial dysfunction in cell culture systems and in animal models.

Dont have a licence yet? Then find out more about our products and how to get one now:

Springer Professional "Wirtschaft+Technik"

Online-Abonnement

Mit Springer Professional "Wirtschaft+Technik" erhalten Sie Zugriff auf:

über 102.000 Bücher
über 537 Zeitschriften

aus folgenden Fachgebieten:

Automobil + Motoren
Bauwesen + Immobilien
Business IT + Informatik
Elektrotechnik + Elektronik
Energie + Nachhaltigkeit
Finance + Banking
Management + Führung
Marketing + Vertrieb
Maschinenbau + Werkstoffe
Versicherung + Risiko

Jetzt Wissensvorsprung sichern!

inform now

Springer Professional "Technik"

Online-Abonnement

Mit Springer Professional "Technik" erhalten Sie Zugriff auf:

über 67.000 Bücher
über 390 Zeitschriften

aus folgenden Fachgebieten:

Automobil + Motoren
Bauwesen + Immobilien
Business IT + Informatik
Elektrotechnik + Elektronik
Energie + Nachhaltigkeit
Maschinenbau + Werkstoffe

Jetzt Wissensvorsprung sichern!

inform now

previous chapter Effects of Hemoglobin-Based Oxygen Carriers on Blood Coagulation

next chapter HBOC Interferences with Routine Clinical Laboratory Tests

Alayash AI (1999) Hemoglobin-based blood substitutes: oxygen carriers, pressor agents, or oxidants? Nat Biotech 17:545–549CrossRef

Alayash AI, Ryan BA, Cashon RE (1998) Peroxynitrite-mediated heme oxidation and protein modification of native and chemically modified hemoglobins. Arch Biochem Biophys 349:65–73CrossRef

Alayash AI, D’Agnillo F, Buehler PW (2007) First-generation blood substitutes: what have we learned? Biochemical and physiological perspectives. Expert Opin Biol Ther 7:665–675CrossRef

Baldwin AL, Wiley EB, Alayash AI (2003) Comparison of the effects of two hemoglobin-based O2 carriers on intestinal integrity and microvascular leakage. Am J Physiol (Heart Circ Physiol) 283:H1292–H1301

Baldwin AL, Wiley EB, Alayash AI (2004) Differential effects of sodium selenite in reducing tissue damage caused by three hemoglobin-based oxygen carriers. J Appl Physiol 96:893–903CrossRef

Balla G, Vercellotti GM, Muller-Eberhard U, Eaton J, Jacob HS (1991) Exposure of endothelial cells to free heme potentiates damage mediated by granulocytes and toxic oxygen species. Lab Invest 64:648–655

Balla J, Nath KA, Balla G, Juckett MB, Jacob HS, Vercellotti GM (1995) Endothelial cell heme oxygenase and ferritin induction in rat lung by hemoglobin in vivo. Am J Physiol 268:L321–L327

Balla J, Vercellotti GM, Jeney V, Yachie A, Varga Z, Jacob HS, Eaton JW, Balla G (2007) Heme, heme oxygenase, and ferritin: how the vascular endothelium survives (and dies) in an iron-rich environment. Antioxid Redox Signal 9:2119–2137CrossRef

Basu S, Grubina R, Huang J, Conradie J, Huang Z, Jeffers A, Jiang A, He X, Azarov I, Seibert R, Mehta A, Patel R, King SB, Hogg N, Ghosh A, Gladwin MT, Kim-Shapiro DB (2007) Catalytic generation of N2O3 by the concerted nitrite reductase and anhydrase activity of hemoglobin. Nat Chem Biol 3:785–794CrossRef

Beckman JS, Koppenol WH (1996) Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol Cell Physiol 271:C1424–C1437

Biro GP (2012) Adverse HBOC-endothelial dysfunction synergism: a possible contributor to adverse clinical outcomes? Curr Drug Discov Technol 9:194–203CrossRef

Biro GP, Ou C, Ryan-Macfarlane C, Anderson PJ (1995) Oxyradical generation after resuscitation of hemorrhagic shock with blood or stromafree hemoglobin. Artif Cells Blood Substit Immobil Biotechnol 23:631–645CrossRef

Boretti FS, Buehler PW, D’Agnillo F, Kluge K, Glaus T, Butt OI, Jia Y, Goede J, Pereira CP, Maggiorini M et al (2009) Sequestration of extracellular hemoglobin within a haptoglobin complex decreases its hypertensive and oxidative effects in dogs and guinea pigs. J Clin Invest 119:2271–2280

Buehler PW, D’Agnillo F (2010) Toxicological consequences of extracellular hemoglobin: biochemical and physiological perspectives. Antioxid Redox Signal 12:275–291CrossRef

Buehler PW, D’Agnillo F, Hoffman V, Alayash AI (2007) Effects of endogenous ascorbate on oxidation, oxygenation, and toxicokinetics of cell-free modified hemoglobin after exchange transfusion in rat and guinea pig. J Pharmacol Exp Ther 323:49–60CrossRef

Buehler PW, D’Agnillo F, Schaer DJ (2010) Hemoglobin-based oxygen carriers: from mechanisms of toxicity and clearance to rational drug design. Trends Mol Med 2010 16:447–457

Buehler PW, Butt OI, D’Agnillo F (2011) Sodium nitrite induces acute central nervous system toxicity in guinea pigs exposed to systemic cell-free hemoglobin. Biochem Biophys Res Commun 409:412–417CrossRef

Buehler PW, Baek JH, Lisk C, Connor I, Sullivan T, Kominsky D, Majka S, Stenmark KR, Nozik-Grayck E, Bonaventura J et al (2012) Free hemoglobin induction of pulmonary vascular disease: evidence for an inflammatory mechanism. Am J Physiol Lung Cell Mol Physiol 303:L312–L326CrossRef

Burhop K, Gordon D, Estep T (2004) Review of hemoglobin-induced myocardial lesions. Artif Cells Blood Substit Immobil Biotechnol 32:353–374CrossRef

Butt OI, Buehler PW, D’Agnillo F (2010) Differential induction of renal heme oxygenase and ferritin in ascorbate and nonascorbate producing species transfused with modified cell-free hemoglobin. Antioxid Redox Signal 12:199–208CrossRef

Butt OI, Buehler PW, D’Agnillo F (2011) Blood-brain barrier disruption and oxidative stress in guinea pig after systemic exposure to modified cell-free hemoglobin. Am J Pathol 178:1316–1328CrossRef

Cabrales P, Friedman JM (2013) HBOC vasoactivity: interplay between nitric oxide scavenging and capacity to generate bioactive nitric oxide species. Antioxid Redox Signal [Epub ahead of print]

D’Agnillo F, Wood F, Porras C, Macdonald VW, Alayash AI (2000) Effects of hypoxia and glutathione depletion on hemoglobin- and myoglobin-mediated oxidative stress toward endothelium. Biochim Biophys Acta 1495:150–159CrossRef

D’Agnillo F (2004) Redox active hemoglobin enhances lipopolysaccharide-induced injury to cultured bovine endothelial cells. Am J Physiol Heart Circ Physiol 287:H1875–H1882CrossRef

D’Agnillo F, Alayash AI (2000) Interactions of hemoglobin with hydrogen peroxide alters thiol levels and course of endothelial cell death. Am J Physiol Heart Circ Physiol 279:H1880–H1889

D’Agnillo F, Alayash AI (2001) Redox cycling of diaspirin cross-linked hemoglobin induces G2/M arrest and apoptosis in cultured endothelial cells. Blood 98:3315–3323CrossRef

D’Agnillo F, Alayash AI (2002) A role for the myoglobin redox cycle in the induction of endothelial cell apoptosis. Free Radic Biol Med 33:1153–1164CrossRef

D’Agnillo F, Chang TM (1998a) Absence of hemoprotein-associated free radical events following oxidant challenge of crosslinked hemoglobin-superoxide dismutase catalase. Free Radic Biol Med 24:906–912CrossRef

D’Agnillo F, Chang TMS (1998b) Polyhemoglobin-superoxide dismutase-catalase as a blood substitute with antioxidant properties. Nat Biotechnol 16:667–671CrossRef

Deskur E, Przywarska I, Dylewicz P, Szcześniak L, Rychlewski T, Wilk M, Wysocki H (1998) Exercise-induced increase in hydrogen peroxide plasma levels is diminished by endurance training after myocardial infarction. Int J Cardiol 67:219–224CrossRef

Dunne J, Caron A, Menu P, Alayash AI, Buehler PW, Wilson MT, Silaghi-Dumitrescu R, Faivre B, Cooper CE (2006) Ascorbate removes key precursors to oxidative damage by cell-free haemoglobin in vitro and in vivo. Biochem J 399:513–524CrossRef

Exner M, Herold S (2000) Kinetic and mechanistic studies of the peroxynitrite-mediated oxidation of oxymyoglobin and oxyhemoglobin. Chem Res Toxicol 13:287–293CrossRef

Faivre B, Menu P, Labrude P, Grandgeorge M, Vigneron C (1994) Methemoglobin formation after administration of hemoglobin conjugated to carboxylate dextran in guinea pigs. Attempts to prevent the oxidation of hemoglobin. Artif Cells Blood Substit Immobil Biotechnol 22:551–558CrossRef

Foresti R, Bains S, Sulc F, Farmer PJ, Green CJ, Motterlini R (2006) The interaction of nitric oxide with distinct hemoglobins differentially amplifies endothelial heme uptake and heme oxygenase-1 expression. J Pharmacol Exp Ther 317:1125–1133CrossRef

Giulivi C, Davies KJA (1994) Hydrogen peroxide-mediated ferrylhemoglobin generation in vitro and in red blood cells. Methods Enzymol 231:490–496CrossRef

González-Mariscal L, Quirós M, Díaz-Coránguez M (2011) ZO proteins and redox-dependent processes. Antioxid Redox Signal 15:1235–1253CrossRef

Granger DN, Korthius RJ (1995) Physiologic mechanisms of postischemic tissue injury. Annu Rev Physiol 57:311–332CrossRef

Gutteridge JMC (1986) Iron promoters of the Fenton reaction and lipid peroxidation can be released from hemoglobin by peroxides. FEBS Lett 201:291–295CrossRef

Halliwell B, Clement MV, Long LH (2000) Hydrogen peroxide in the human body. FEBS Lett 486:10–13CrossRef

Higdon AN, Benavides GA, Chacko BK, Ouyang X, Johnson MS, Landar A, Zhang J, Darley-Usmar VM (2012) Hemin causes mitochondrial dysfunction in endothelial cells through promoting lipid peroxidation: the protective role of autophagy. Am J Physiol Heart Circ Physiol 302:H1394–H1409CrossRef

Jahr JS, Akha AS, Holtby RJ (2012) Crosslinked, polymerized, and PEG-conjugated hemoglobin-based oxygen carriers: clinical safety and efficacy of recent and current products. Curr Drug Discov Technol 9:158–165CrossRef

Jia Y, Buehler PW, Boykins RA, Venable RM, Alayash AI (2007) Structural basis of peroxide-mediated changes in human hemoglobin: a novel oxidative pathway. J Biol Chem 282:4894–4907CrossRef

Keszler A, Piknova B, Schechter AN, Hogg N (2008) The reaction between nitrite and oxyhemoglobin: a mechanistic study. J Biol Chem 283:9615–9622CrossRef

Lacy F, O’Connor DT, Schmid-Schönbein GW (1998) Plasma hydrogen peroxide production in hypertensives and normotensive subjects at genetic risk of hypertension. J Hypertens 16:291–303CrossRef

Lee R, Neya K, Svizzero TA, Vlahakes GJ (1995) Limitations of the efficacy of hemoglobin-based oxygen-carrying solutions. J Appl Physiol 79:236–242

Linberg R, Conover CD, Shum KL, Shorr RG (1998) Hemoglobin based oxygen carriers: how much methemoglobin is too much? Artif Cells Blood Substit Immobil Biotechnol 26:133–148CrossRef

Ma Q (2013) Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol 53:401–426CrossRef

Maitra D, Byun J, Andreana PR, Abdulhamid I, Diamond MP, Saed GM, Pennathur S, Abu-Soud HM (2011) Reaction of hemoglobin with HOCl: mechanism of heme destruction and free iron release. Free Radic Biol Med 51:374–386CrossRef

Maitra D, Abdulhamid I, Diamond MP, Saed GM, Abu-Soud HM (2012) Melatonin attenuates hypochlorous acid-mediated heme destruction, free iron release, and protein aggregation in hemoglobin. J Pineal Res 53:198–205CrossRef

McLeod LL, Alayash AI (1999) Detection of a ferrylhemoglobin intermediate in an endothelial cell model after hypoxia-reoxygenation. Am J Physiol 277:H92–H99

Minneci PC, Deans KJ, Shiva S, Zhi H, Banks SM, Kern S, Natanson C, Solomon SB, Gladwin MT (2008) Nitrite reductase activity of hemoglobin as a systemic nitric oxide generator mechanism to detoxify plasma hemoglobin produced during hemolysis. Am J Physiol Heart Circ Physiol 295:H743–H754CrossRef

Moon-Massat P, Scultetus A, Arnaud F, Brown A, Haque A, Saha B, Kim B, Sagini E, McGwin G Jr, Auker C, McCarron R, Freilich D (2012) The effect HBOC-201 and sodium nitrite resuscitation after uncontrolled haemorrhagic shock in swine. Injury 43:638–647CrossRef

Moore KP, Holt SG, Patel RP, Svistunenko DA, Zackert W, Goodier D, Reeder BJ, Clozel M, Anand R, Cooper CE, Morrow JD, Wilson MT, Darley-Usmar V, Roberts LJ (1998) A causative role for redox cycling of myoglobin and its inhibition by alkalinization in the pathogenesis and treatment of rhabdomyolysis-induced renal failure. J Biol Chem 273:31731–31737CrossRef

Motterlini R, MacDonald VW (1993) Cell-free hemoglobin potentiates acetylcholine-induced coronary vasoconstriction in rabbit hearts. J Appl Physiol 75:2224–2233

Motterlini R, Foresti R, Vandegriff K, Intaglietta M, Winslow RM (1995) Oxidative-stress response in vascular endothelial cells exposed to acellular hemoglobin solutions. Am J Physiol 269:H648–H655

Nagy E, Eaton JW, Jeney V, Soares MP, Varga Z, Galajda Z, Szentmiklósi J, Méhes G, Csonka T, Smith A, Vercellotti GM, Balla G, Balla J (2010) Red cells, hemoglobin, heme, iron, and atherogenesis. Arterioscler Thromb Vasc Biol 30:1347–1353CrossRef

Piknova B, Keszler A, Hogg N, Schechter AN (2009) The reaction of cell-free oxyhemoglobin with nitrite under physiologically relevant conditions: Implications for nitrite-based therapies. Nitric Oxide 20:88–94CrossRef

Powanda DD, Chang TM (2002) Cross-linked polyhemoglobin-superoxide dismutase-catalase supplies oxygen without causing blood-brain barrier disruption or brain edema in a rat model of transient global brain ischemia-reperfusion. Artif Cells Blood Substit Immobil Biotechnol 30:23–37CrossRef

Reeder BJ (2010) The redox activity of hemoglobins: from physiologic functions to pathologic mechanisms. Antioxid Redox Signal 13:1087–10123CrossRef

Reeder BJ, Wilson MT (2005) Hemoglobin and myoglobin associated oxidative stress: from molecular mechanisms to disease States. Curr Med Chem 12:2741–2751CrossRef

Reeder BJ, Sharpe MA, Kay AD, Kerr M, Moore K, Wilson MT (2002) Toxicity of myoglobin and haemoglobin: oxidative stress in patients with rhabdomyolysis and subarachnoid haemorrhage. Biochem Soc Trans 30:745–748CrossRef

Riess JG (2001) Oxygen carriers (‘‘blood substitutes’’)—raison d’etre, chemistry, and some physiology. Chem Rev 101:2797–2920CrossRef

Rifkind JM, Ramasamy S, Manoharan PT, Nagababu E, Mohanty JG (2004) Redox reactions of hemoglobin. Antioxid Redox Signal 6:657–666CrossRef

Rodriguez C, Vitturi DA, He J, Vandromme M, Brandon A, Hutchings A, Rue LW 3rd, Kerby JD, Patel RP (2009) Sodium nitrite therapy attenuates the hypertensive effects of HBOC-201 via nitrite reduction. Biochem J 422:423–432

Silva G, Jeney V, Chora A, Larsen R, Balla J, Soares MP (2009) Oxidized hemoglobin is an endogenous proinflammatory agonist that targets vascular endothelial cells. J Biol Chem 284:29582–29595CrossRef

Silverman TA, Weiskopf RB, Planning Committee and the Speakers (2009) Hemoglobin-based oxygen carriers: current status and future directions. Anesthesiology 111:946–963

Simoni J, Simoni G, Garcia EL, Prien SD, Tran RM, Feola M, Shires GT (1995) Protective effect of selenium on hemoglobin-mediated lipid peroxidation in vivo. Artif Cells Blood Substit Immobil Biotechnol 23:469–486CrossRef

Simoni J, Simoni G, Lox CD, Prien SD, Tran R, Shires GT (1997) Expression of adhesion molecules and von Willebrand factor in human coronary artery endothelial cells incubated with differently modified hemoglobin solutions. Artif Cells Blood Substit Immobil Biotechnol 25:211–225CrossRef

Simoni J, Simoni G, Wesson DE, Griswold JA, Feola M (2000) A novel hemoglobin-adenosine-glutathione based blood substitute: evaluation of its effects on human blood ex vivo. ASAIO J 46:679–692CrossRef

Smith CD, Schuschereba ST, Hess JR, McKinney LA, Bunch D, Bowan PD (1990) Liver and kidney injury after adminstration of hemoglobin cross-linked with bis(3,5-dibromosalicyl)fumarate. Biomater Artif Cells Artif Organs 18:251–261

Sprung J, Kindscher JD, Wahr JA, Levy JH, Monk TG, Moritz MW, O’Hara PJ (2002) The use of bovine hemoglobin glutamer-250 (Hemopure) in surgical patients: results of a multicenter, randomized, single-blinded trial. Anesth Analg 94:799–808CrossRef

Tsukimori K, Yoshitomi T, Morokuma S, Fukushima K, Wake N (2008) Serum uric acid levels correlate with plasma hydrogen peroxide and protein carbonyl levels in preeclampsia. Am J Hypertens 21:1343–1346CrossRef

Usatyuk PV, Natarajan V (2012) Hydroxyalkenals and oxidized phospholipids modulation of endothelial cytoskeleton, focal adhesion and adherens junction proteins in regulating endothelial barrier function. Microvasc Res 83:45–55CrossRef

Wagener FA, Feldman E, de Witte T, Abraham NG (1997) Heme induces the expression of adhesion molecules ICAM-1, VCAM-1, and E selectin in vascular endothelial cells. Proc Soc Exp Biol Med 216:456–463CrossRef

Yu B, Shahid M, Egorina EM, Sovershaev MA, Raher MJ, Lei C, Wu MX, Bloch KD, Zapol WM (2010) Endothelial dysfunction enhances vasoconstriction due to scavenging of nitric oxide by a hemoglobin-based oxygen carrier. Anesthesiology 112:586–594CrossRef

Title: Redox Activity of Cell-Free Hemoglobin: Implications for Vascular Oxidative Stress and Endothelial Dysfunction
Author: Felice D’Agnillo
Publisher: Springer Berlin Heidelberg
Book: Hemoglobin-Based Oxygen Carriers as Red Cell Substitutes and Oxygen Therapeutics
Print ISBN: 978-3-642-40716-1

Electronic ISBN: 978-3-642-40717-8

Copyright Year: 2013
DOI: https://doi.org/10.1007/978-3-642-40717-8_35

Springer Professional

Abstract

Please log in to get access to your license.

Dont have a licence yet? Then find out more about our products and how to get one now:

Springer Professional "Wirtschaft+Technik"

Springer Professional "Technik"

Premium Partners