|
|
|
|
HEME OXYGENASE AND CARBON MONOXIDE: THE PROTECTION OR THE INJURY OF THE CELLS?
T.V.Kukoba, A.A.Moibenko
A.A.Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kiуv.
![](/images/cite.png)
Abstract
Heme oxygenase (HO) catalyzes the conversion of heme
to carbon monoxide, iron, and biliverdin, which is
immediately reduced to bilirubin. Three HO active
isozymes exist: HO-1, an inducible heat shock protein
(HSP32), and HO-2 and HO-3, which are constitutive
and highly concentrated in neurons, spleen and liver.
Heme oxygenase-1 is an inducible enzyme that catalyzes
heme degradation and has been proposed to play a
role in protecting cells against oxidative stress-related
injury. The mechanism(s) of protection is not completely elucidated, although it is suggested that one or
more of the catalytic by-products provide antioxidant
functions either directly or indirectly. The role played
by heme oxygenase in tissue pathology is determined
by a delicate balance between the injurious and protective actions of heme, bilirubin, CO, and Fe 2+. Autors
review the functional role of HO and its derivates in
cells biology and its real potential application to
pathological conditions.
Keywords:
HEME OXYGENASE, CARBON MONOXIDE, PROTECTION OR THE INJURY
References
- Agarwal A., Kim Y., Matas A.J. et al. Gas-generating systems in acute renal allograft rejection in the rat: co-induction of heme oxygenase and nitric oxide synthase // Transplantation. – 1996. – 61, № 1. – P. 93-98.
- Balla J., Jacob H.S., Balla G. et al. Endothelialcell heme uptake from heme proteins: induction of sensitization and desensitization to oxidant damage // Proc. Natl. Acad. Sci. USA – 1993. –90, № 20. – P. 9285-9289.
- Balla G., Jacob H.S., Balla J. Induction of endothelial ferritin: a cytoprotective antioxidant stratagem of the vessel wall // J. Biol. Chem. – 1992. –267, № 25. – P. 18148-18153.
- Baraсano D.E., Snyder H.H. Neural roles for heme oxygenase: Contrasts to nitric oxide synthase //Proc. Natl. Acad. Sci. USA. – 2001. – 98, Issue 20, September 25. – P. 10996-11002.
- Baraсano D.E., Wolosker H., Bae B.-Il. et al. Mammalian Iron ATPase Induced by Iron // J. Biol. Chem. – 2000. – 275, Issue 20, May, 19. –P. 15166-15173.
- Battish R., Cao G-Y., Lynn R.B. et al. Heme Oxygenase-2 distribution in anorectum: colocalisation with neuronal nitric oxide synthase // Amer. J. Physiol. Gasterointest. Liver Prysiol. –2000. – 278. – P. G 148-G155.
- Benjamin I.J., McMillan D.R. Stress (Heat Shock )Proteins Molecular Chaperones in Cardiovascular Biology and Disease // Circulat. Res. – 1998. –83, № 2. – P. 117–132.
- Brouard S., Otterbein L.E., Anrather J. et al. Carbon Monoxide Generated by Heme Oxygenase 1 Suppresses Endothelial Cell Apoptosis //J. Exp. Med. – 2000. – 192, № 7. – P. 1015–1026.
- 9. Cardell L.O., Lou Y.P., Takeyama K. et al. Carbon monoxide, a cyclic GMP-related messenger, involved in hypoxic bronchodilation in vivo // Pulm.Pharmacol. Therap. – 1998. – 11, № 4. – P. 309-315.
- 10. Carraway M.S., Ghio A.J., Carter J.D. et al. Expression of heme oxygenase-1 in the lung in chronic hypoxia // Amer. J. Physiol. Lung.Cell. Mol. Physiol. – 2000. – 278, № 4. –P. L806–L812.
- Chen K., Gunter K., Maines M.D. Neurons overexpressing heme oxygenase-1 resist oxidative stressmediated cell death // J. Neurochem. – 2000. –75, № 1. – P. 304–313.
- Chen W., Hunt D.M., Lu H. et al. Expression of antioxidant protective proteins in the rat retina during prenatal and postnatal development //Invest. Opthalmol. Vis. Sci. – 1999. – 40, № 3. –P. 744–751.
- Choi, A. M.K. Heme Oxygenase-1 Protects the Heart / Circulat.Res. – 2001. – 89, July,20. – P. 105–107.
- Clark J.E., Foresti R., Sarathchandra P. et al.Heme oxygenase-1-derived bilirubin ameliorates postischemic myocardial dysfunction // Amer.J.Physiol. – 2000. – 278, Issue 2. – P. H643–H651.
- Coceani F. Carbon Monoxide in Vasoregulation.The Promise and the Challenge // Circulat. Res. –2000. – 86, № 12. – P. 1184 – 1186.
- Cruse I., Maines M.D. Evidence suggesting that the two forms of heme oxygenase are products of different genes // J. Biol. Chem. – 1988. – 263,№ 7. – P. 3348-3353.
- Csonka C., Varga E., Kovacs. P. et al. Heme oxygenase and cardiac function in ischemic/reperfused rat hearts // Free Rad. Biol. Med. – 1999. –27, № 1–2. – P. 119–126.
- Ding Y., McCoubrey W.K., Maines M.D. Interaction of heme oxygenase-2 with nitric oxide donors // Eur.J. Biochem. – 1999. – 264, № 9. – P. 854–861.
- 19. Doi K., Akaike T., Fujii S. et al. Induction of haem oxygenase-1 nitric oxide and ischaemia in experimental solid tumours and implications for tumour growth // Brit. J. Cancer. – 1999. – 80,№ 12. – P. 1945–1954.
- 20. Dong Z., Lavrovsky Y., Venkatachalam M.A. et al. Heme Oxygenase-1 in Tissue Pathology // Amer.J. Phatol. – 2000. – 156, № 5. – P. 1485–1488.
- Dorй S., Takahashi M., Ferris C.D. et al. Bilirubin, formed by activation of heme oxygenase-2, protects neurons against oxidative stress injury // Neurobiology. – 1999. – 96, Issue 5,March 2. – P. 2445–2450.
- Downard P.J., Wilson M.A., Spain D.A. et al. Heme oxygenase-dependent carbon monoxide production is a hepatic adaptive response to sepsis //J. Surg. Res. – 1997. – 71, № 1. – P. 7–12.
- Durante W., Kroll M.H., Christodoulides N. et al. Nitric Oxide Induces Heme Oxigenase-1 Gene Expression and Carbon Monoxide Production in Vascular Smooth Muscle Cells // Circulat. Res. –1997 – 80, № 4. – P. 557-564.
- Duke H.N., Killick E.M. Pulmonary vasomotor responses of isolated perfused cat lungs to anoxia // J. Physiol. – 1952. – 117. – P. 303–316.
- Eisenstein R.S., Garcia-Mayol D., Pettingell W. et al. Regulation of ferritin and heme oxygenase in rat fibroblasts by different forms of iron // Proc. Natl.Acad. Sci. USA. – 1991. - 88, № 2. – P. 688-692.
- Elbirt K.K., Whitmarsh A.J., Davis R.J. et al. Mechanism of Sodium Arsenite-mediated Induction of Heme Oxygenase-1 in Hepatoma Cells. Role of mitogen-activated protein kinases // J. Biol. Chem. –1998. – 273, Issue 15, April 10. – P. 8922–8931.
- Ernst A., Zibrak J.D. Carbon monoxide poisoning // N. Engl. J. Med. – 1998. – 339, № 22. – P. 1603–1608.
- Foresti R., Clark J.E., Green C.J. et al. Thiol compounds interact with nitric oxide in regulating heme oxygenase-1 induction in endothelial cells.Involvement of superoxide and peroxynitrite anions// J. Biol. Chem. – 1997. – 272, Issue 7. –P. 18411-18417.
- 29. Foresti, R., Sarathchandra P., Clark J.E. et al. Peroxynitrite induces haem oxygenase-1 in vascular endothelial cells: a link to apoptosis // Biochem. J. – 1999. – 339, May 1 (Pt 3). – P. 729–736.
- 30. Furchgott R.F., Jothianandan D. Endotheliumdependent and independent vasodilation involving cyclic GMP: relaxation induced by nitric oxide,carbon monoxide and light // Blood. Vessels. –1991. – 28, № 1–3. – P. 52–61.
- Geddes J.W., Pettigrew L.C., Holtz M.L. et al. Permanent focal and transient global cerebral ischemia increase glial and neuronal expression of heme oxygenase1, but not heme oxygenase-2, protein in rat brain //Neurosci. Lett. – 1996. – 210, № 3. – P.205- 208.
- Gong P., Hu B., Stewart D. et al. Cobalt induceheme oxygenase-1 expression by a hypoxia-inducible factor-independent mechanism in Chinese hamster ovary cells: regulation by Nrf2 and MafG transcription factors // J.Biol.Chem.–2001. – 276(29), № 8 – P. 27018–27025.
- Gopinathan V., Miller N.J., Milner A.D. et al.Bilirubin and ascorbate antioxidant activity in neonatal plasma // FEBS Lett. – 1994. – 349,№ 2. – P. 197–200.
- Hangaishi M, Ishizaka N, Aizawa T. et al. Induction of heme oxygenase-1 can act protectively against cardiac ischemia/reperfusion in vivo // Biochem. and Biophys. Res. Commun. – 2000. – 279,№ 2. – P. 582–588.
- Henningsson R., Alm P., Lundquist I. Occurrence and putative hormone regulatory function of a constitutive heme oxygenase in rat pancreatic islets // Amer. J. Physiol. Cell. Physiol. – 1997. –273, № 2 (Pt 1). – P. C703-C709.
- Horvath I., Donnelly L.E., Kiss A. et al. Raised levels of exhaled carbon monoxide are associated with an increased expression of heme oxygenase-1 in airway macrophages in asthma: a new marker of oxidative stress // Thorax. – 1998. – 53,№ 8. – P. 668-672.
- Ishizaka N., de Leon H., Laursen J.B. et al. Angiotensin II-induced hypertension increases heme oxygenase-1 expression in rat aorta // Circulation. – 1997. – 96, № 6. – P. 1923–1929.
- Jandl J.H. Physiology of red cells. – In: Blood. –textbook of hematology / Ed. J.H.Jandl. – Boston:Mass, 1987. – P. 89–92.
- 39. Johnson R.A., Lavesa M., Askari B. et al. A heme oxygenase product, presumably carbon monoxide, mediates a vasodepressor function in rats //Hypertension. – 1995. – 25, №2. – P.166–169.
- 40. Keyse S.M. Tyrrell R.M. Heme oxygenase is the major 32-KDA stress protein induced in human skin fibroblasts by UVA radiation, hydrogen peroxide, and sodium arsenite // Proc. Natl. Acad.Sci. USA. – 1989. – 86, № 1. – P. 99–103.
- Lee P.J., Alam J., Wiegand G.W. et al. Overexpression of heme oxygenase-1 expression in human pulmonary epithelial cells results in cell growth arrest and increased resistance to hyperoxia //Ibid. – 1996. – 93, № 19. – P. 10393–10398.
- Levere R.D., Staudinger R., Loewy G. et al. Elevated levels of heme oxygenase activity and mRNA in peripheral blood adherent cells of acquired immunodeficiency syndrome patients // Amer. J. Hematol. – 1993. – 43, № 1. – P. 19–23.
- Llesuy S.F., Tomaro M.L. Heme oxygenase and oxidative stress. Evidence of involvement of bilirubin as physiological protector against oxidative damage // Biochim. and Biophys. Acta. –1994. –1223, № 1. – P. 9–14.
- Maines M.D., Mayer R.D., Ewing J.F. et al. Induction of kidney heme oxygenase-1 (HSP32) mRNA and protein by ischemia/reperfusion: possible role of heme as both promotor of tissue damage and regulator of HSP32 // J.Pharmacol. Exp.Therap. 1993. – 264, № 1. – P. 457–462.
- Maines M.D. Heme Oxygenase: Clinical Applications and Functions. Inc. Boca Ration, FL: Press CRC, – 1992. – 266 p.
- Maines M.D., Panahian N. The heme oxygenase system and cellular defense mechanisms. Do HO-1and HO-2 have different functionsα // Adv. Exp.Med. Biol. – 2001. – 502, № 2. – P. 49–72.
- Maines M. D. The heme oxygenase system: a regulator of second messenger gases // Ann. Rev. Pharmacol.Toxicol. – 1997. – 37, № 1. – P. 517–554.
- Maines M.D., Trakshel G.M. Kutty R.K. Characterization of two constitutive forms of rat liver microsomal heme oxygenase: Only one molecular species of the enzyme is inducible // J. Biol.Chem. – 1986. – 261, № 1. – P. 411–419.
- 49. Maines M.D., Raju V.S., Panahian N. Spin Trap (N-t-butil-a-phenylnitrone)-Mediated Suprainduction of Heme Oxigenase-1 in Kidney Ischemia / Reperfusion Model: Role of the Oxygenase in Protection against Oxidative Injury // Pharmacology. – 1999. – 291, № 2. – P. 911–919.
- 50. Marber M. S., Latchman D. S., Walker J. M. et al. Cardiac stress protein elevation 24 hours after brief ischemia or heat stress is associated with resistance to myocardial infarction // Circulation. – 1993. – 88, № 3. – P. 1264–1272.
- Marks G.S. Heme oxygenase: the physiological role of one of its metabolites, carbon monoxide and interactions with zinc protoporphyrin, cobalt protoporphyrin and other metalloporphyrins // Cell. Mol. Biol. – 1994. – 40, № 7. – P. 863–870.
- Maulik N., Sharma H.S., Das D.K. Induction of the haem oxygenase gene expression during the reperfusion of ischemic rat myocardium // J. Mol.Cell. Cardiol. – 1996. – 28, № 6. – P. 1261–1270.
- Mautes A.E., Kim D.H., Sharp F.R. et al. Induction of heme oxygenase-1 (HO-1) in the contused spinal cord of the rat // Brain Res. – 1998. –795, № 1-2. – P. 17-24.
- McCoubrey W.K., Huang T.J., Maines M.D. Isolatoin and characterization of a cDNA from the rat brain that encodes hemoprotein heme oxygenase-3 // Eur. J. Biochem. – 1997. – 247, № 2. –P. 725-732.
- Mireles L.C., Lum M.A., Dennery P.A. Anti- oxidant and cytotoxic effects of bilirubin on neonatal erythrocytes // Pediatr. Res. 1999. – 45,№ 3. – P. 355–436.
- Moray R. A relation of persons killed with subterraneous damps // Phil. Trans. Roy. Soc. London. - 1665. – 1. – P. 44-45.
- Motterlini R., Foresti R., Bassi R. et al. Endothelial Heme Oxygenase-1 Induction by Hypoxia // J. Biol. Chem. – 2000. - 275, Issue 18, № 5. –P. 13613–13620.
- Motterlini R., Foresti R., Intaglietta M. et al. Oxidative-stress response in vascular endothelial cells exposed to acellular hemoglobin solutions //Amer. J. Physiol. Heart Circulat. Physiol. – 1995. –269, № 2 (Pt 2). – P. H648–H655.
- 59. Motterlini R., Foresti R, Intaglietta M. et al. NOmediated activation of heme oxygenase: endogenous cytoprotection against oxidative stress to endothelium // Ibid. – 1996 – 270, № 1 (Pt 2). –P. H107–H114.
- 60. Motterlini R., Gonzales A., Foresti R. et al. Heme oxygenase-1-derived carbon monoxide contributes to the suppression of acute hypertensive responses in vivo // Circulat. Res. – 1998. – 83, № 9. –P. 568–577.
- Nathanson J.A., Scavone C., Scalon C. et al. The cellular Na+ pump as a site of action for carbon monoxide and glutamate: for long-term modulation of cellular activity // Neuron.. – 1995. – 14,№ 1. – P. 781–794.
- Nath K.A., Balla G., Vercellotti G.M. et al. Induction of heme oxygenase is a rapid protectiveresponse in rhabdomyolysis in the rat // J. Clin. Invest. – 1992. – 90, № 1. – P. 267-270.
- Nath K.A., Grande J.P., Croatt A.J. et al. Intracellular targets in heme protein-induced renal injury // Kidney Int. – 1998. – 53, № 1. –P. 100–111.
- Nath K.A., Haggard J.J., Croatt A.J. et al. The indispensability of heme oxygenase-1 (HO-1) in protecting against acute protein-induced toxity in vivo // Amer. Pathol. – 2000. – 156, № 5 –P. 1527–1535.
- Ndisang J.F., Wang R., Vannacci A. et al. Haeme oxygenase-1 and cardiac anaphylaxis // Brit. J.Pharmacol. – 2001. – 134, № 8. – P. 1689–1696.
- Neuzil J., Stocker R. Free and albumin-bound bilirubin are efficient co-antioxidants for alphatocopherol, inhibiting plasma and low density lipoprotein lipid peroxidation // J. Biol. Chem.– 1994. – 269, № 24. – P. 16712–16719.
- Otterbein L.E., Bach F.H., Alam J. et al. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway //Natur. Med. – 2000. – 6, № 4. – P. 422–428.
- Otterbein L.E., Choi A.M.K. Heme oxygenase: colors of defense against cellular stress // Amer.J. Physiol. – 2000. - 279, Issue 6. –P. L1029–L1037.
- 69. Otterbein L.E., Kolls J.K., Mantell L.L. et al. Exogenous administration of heme oxygenase-1 by gene transfer provides protection against hyperoxiainduced lung injury // J. Clin. Invest. – 1999. –103, № 7. – P. 1047–1054.
- 70. Otterbein L., Sylvester S.L., Choi A.M.K. Hemoglobin provides protection against lethal endotoxemia in rats: the role of heme oxygenase-1 //Amer. J.Respirat. Cell. Mol. Biol. – 1995. – 13,№ 5. – P. 595–601.
- Panchenko M.V., Farber H.W., Korn J.H. Induction of heme oxygenase-1 by hypoxia and free radicals in human dermal fibroblasts // Amer. J.Physiol. – 2000. – 278, Issue 1. – P. C92–C101.
- Pataki T., Bak I., Csonka C. et al. Regulation of ventricular fibrillation by heme oxygenase in ischemic/reperfused hearts // Antioxid. Redox. Signal. – 2001. – 3, № 1. – P. 125–34.
- Petrache I., Otterbein LE., Alam J. et al. Heme oxygenase-1 inhibits TNF-a-induced apoptosis in cultured fibroblast // Amer. J. Physiol. Lung Cell Mol. Physiol. – 2000. – 278, Issue 2. – P. 312L-319.
- Polte T., Abate A., Dennery P.A. et al. Heme oxygenase-1 is a cGMP-inducible endothelial protein and mediates the cytoprotective action of nitric oxide // Arterioscler. Thromb. Vascular. Biol. –2000. – 20, № 5. – P. 1209–1215.
- Ponka P., Beaumont C., Richardson D.R. Function and regulation of transferrin and ferritin // Semin.Hematol. – 1998. – 35, № 1. – P. 35–54.
- Poss K.D., Tonegawa S. Reduced stress defense in heme oxygenase-1 deficient cells // Proc. Natl. Acad.Sci. USA. – 1997. – 94, № 9. – P. 10925–10930.
- Premkumar D.R., Smith M.A., Richey P.L. et al. Induction of heme oxygenase-1 mRNA and protein in neocortex and cerebral vessels in Alzheimer’s disease // J. Neurochem. – 1995. – 65, № 3 . –P. 1399–1402.
- Rattan S., Fan Y.P., Chakder S. Mechanism of inhibition of VIP-induced LES relaxation by heme oxygenase inhibitor zinc protoporphyrin IX //Amer. J. Physiol. – 1999. – 276, №1 ( Pt 1). –P. G138–45.
- 79. Rizzardini M., Terao M., Falciani F. et al. Cytokine induction of haem oxygenase mRNA in mouse liver. Interleukin-1 transcriptionally activates the haem oxygenase gene // Biochem. J. – 1993. –290, March 1(Pt 2). – P. 343–347.
- 80. Rotgers P.A., Vreman H.J., Dennery P.A. et al. Sources of carbon monoxide (CO) in biological system and applications of CO detection technologies // Semin. Perinatol. – 1994. – 18, № 1. –P. 2–10.
- Ryter S.W., Tyrrell R.M. The heme synthesis and degradation pathways: role in oxidant sensitivity. Heme oxygenase has both pro- and antioxidantproperties // Free Rad. Biol. Med. – 2000. – 28,№ 2. – P. 289–309.
- Sammut I. A., Foresti R., Clark J.E. et al. Carbon monoxide is a major contributor to the regulation of vascular tone in aortas expressing high levels of haeme oxygenase-1 // Brit. J. Pharmacol. – 1998. –125, № 7. – P. 1437–1444.
- Sato H., Siow R.C., Bartlett S. et al. Expression of stress proteins heme oxygenase-1 and -2 in acute pancreatitis and pancreatic islet betaTC3 and acinar AR42J cells // FEBS Lett. – 1997. – 405,№ 2. – P. 219–223.
- Siow R.C.M., Sata H., Mann G.E. Heme oxygenasecarbon monoxide signalling pathway in atherosclerosis: anti-atherogenic actions of bilirubin and carbon monoxideα // Cardiovascular. Res. –1999. – 41, № 2. – P. 385–394.
- Smith M.A., Kutty R.K., Richey P.L.et al. Heme oxygenase-1 is associated with the neurofibrillary pathology of Alzheimer’s disease // Amer. J.Pathol. – 1994. – 145, № 1. – P. 42–47.
- Snyder S.H., Jaffrey S.R., Zakhary R. Nitric oxide and carbon monoxide: parallel roles as neural messengers // Brain. Res. Rev. – 1998. – № 2-3. –P. 167-175.
- Soares M.P., Lin Y., Anrather J. et al. Expression of heme oxygenase-1 can determine cardiac xenograft survival // Natur. Med. – 1998. - 4, № 9. – P. 1073–1077.
- Stocker R., Yamamoto Y., McDonagh A.F. et al. Bilirubin is an antioxidant of possible physiological importance // Science. – 1987. – 235, Feb. 27 (4792). – P. 1043–1046.
- 89. Stupfel M., Bouley G. Physiological and biochemical effects on rats and mice exposed to small concentrations of carbon monoxide for long periods // Ann. NY Acad. Sci. – 1970. – 174, № 1. –P. 342–368.
- 90. Suttner D.M., Dennery P.A. Reversal of HO-1related cytoprotection with increased expression is due to reactive iron // FASEB J. – 1999. – 13,№ 13. – P. 1800–1809.
- 91. Suttner D.M., Sridhar K., Lee C.S. et al. P.A. Protective effects of transient HO-1 overexpression on susceptibility to oxygen toxicity in lung cells // Amer. J. Physiol. Lung Cell. Mol. Physiol. –1999. – 276, № 3 (Pt 1). – P. L443–L451.
- 92. Thorup C., Jones S.L, Gross S.S. et al. Carbon monoxide induces vasodilation and nitric oxide release but suppresses endothelial NOS // Amer.J. Physiol. – 1999. – 277, Issue 6. – P. F882–F889.
- 93. Vachharajani T.J., Work J., Sekutz A.C. et al. Heme oxygenase modulates selectin expression in different regional vascular beds // Amer. J. Physiol. Heart Circulat. Physiol. – 2000. – 278, № 5. –P. H1613–H1617.
- 94. Verma A., Hirsch D.J., Glatt C.E. et al. Carbon monoxide: a putative neural messenger // Science. – 1993. – 259, Jan 15 (5093). – P. 381–384.
- 95. Vile G.F., Tyrrell R.M. Oxidative stress resulting from ultraviolet A irradiation of human skin fibroblasts leads to a heme oxygenase-dependent increase in ferritin // J. Biol. Chem. – 1993. – 268,№ 2. – P. 14678–14681.
- 96. Vreman H.J., Wong R.J., Sanesi C.A. et al. Simultaneous production of carbon monoxide and thiobarbituric acid reactive substances in rat tissue preparations by an iron-ascorbate system // Can. J. Physiol.and Pharmacol. – 1998. – 76, №12. – P. 1057–1065.
- 97. Wang L.J., Lee T.S., Lee F.Y. et al. Expression of heme oxygenase-1 in atherosclerotic lesions //Amer. J. Pathol. – 1998. – 152, № 3. – P. 711–720.
- 98. Wang R., Wang Z., Wu L. et al. Reduced Vasorelaxant Effect of Carbon Monoxide in Diabetes and the Underlying Mechanisms // Diabetes. –2001. – 50, № 1. – P. 166–174.
- 99. Wang R. Resurgence of carbon monoxide: an endogenous gaseous vasorelaxig factor // Can.J. Pharmacol. – 1998. – 76, p.1. – P. 1–15.
- 100. Yamada N., Yamaya M., Okinaga S. et al. Protective Effects of Heme Oxygenase-1 against Oxidant-Induced Injury in the Cultured Human Tracheal Epithelium // Amer. J. Respirat. Cell. MolBoil., – 1999. – 21, № 3. – p. 428 –435.
- 101. Yamada N., Yamaya M., Okinaga S. et al. Microsatellite polymorphism in the heme oxygenase-1 ene promoter is associated with susceptibility to emphysema // Amer. J. Hum. Genet. – 2000. –66, № 1. – P. 187–195.
- 102. Yachie A., Niida Y., Wada T. et al. Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency // J. Clin.Invest. – 1999. – 103, № 1. – P. 129–135.
- 103. Yet S.F., Pellacani A., Patterson C. et al. Induction of heme oxygenase-1 expression in vascular smooth uscle cells: a link to endotoxic shock // J. Biol. Chem. - 1997. – 272, № 7. – P. 4295–4301.
- 104. Yet S.F., Tian R., Layne M.D. et al. Cardiac-specific expression of heme oxygenase-1 protects against ischemia and reperfusion injury in trans-genic mice // Circulat. Res. – 2001. – 89, № 7. – P. 168–173.
|
|
|
|
|
|
|