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Mini-Review

Ist Sauerstoffmangel immer nur schädlich?

Published Online:October 16, 2018https://doi.org/10.1024/1661-8157/a003070

Abstract

Zusammenfassung. Die Aufgabe des Kreislaufs ist die Versorgung von Gewebe mit Sauerstoff und Nährstoffen. Zustände des Sauerstoffmangels (Hypoxie) werden als bedrohlich erachtet, da abhängig vom Ausprägungsgrad Zellen absterben, sei es durch apoptotische oder nekrotische Vorgänge. Dem versucht das Gewebe durch evolutionär erhaltene Signalwege entgegenzuwirken, z.B. über den nukleären Hypoxie-induzierbaren Faktor, der das Gewebe schützen soll, indem er das Überleben der Zellen fördert und gleichzeitig in Angiogenese, Hämatogenese und Stoffwechselprozesse eingreift. Neuere Erkenntnisse weisen darauf hin, dass gerade diese konservierten Signalwege auch therapeutische Ansätze in der Wundheilung von Knochen und Haut sowie in der Regeneration von Geweben, z.B. der Leber, und dem hämatopoetischen System, bedeuten können.


Is Oxygen Deficiency Always Harmful?

Abstract. The role of the cardiovascular circulation is to supply tissue with oxygen and nutrients. Oxygen deficiency (hypoxia) is considered life-threatening, since cells die, either through apoptotic or necrotic processes. Tissue tries to counteract this by means of evolutionary signalling pathways, such as the nuclear hypoxia-inducible factor, which protects the tissue by promoting cell survival strategies and simultaneously intervening in angiogenesis, haematogenesis and metabolic processes. Recent findings indicate that these conserved signalling pathways can also function as therapeutic approaches in wound healing of bones and skin, as well as in the regeneration of tissues, e.g. in the liver, and in the hematopoietic system.


Résumé. Le rôle de la circulation est de fournir aux tissus de l’oxygène et des nutriments. Les conditions de carence en oxygène (hypoxie) sont considérées comme menaçantes, car les cellules meurent en fonction de leur degré de développement, soit par des processus apoptotiques ou nécrotiques. Le tissu tente d’y remédier par des voies de signalisation, comme le facteur nucléaire inductible à l’hypoxie unfacteur qui vise à protéger le tissu en favorisant la survie cellulaire et en intervenant simultanément dans l’angiogenèse, l’hématogenèse et les processus métaboliques. Des résultats récents indiquent que ces voies de signalisation peuvent également représenter des approches thérapeutiques dans la cicatrisation des os et de la peau, ainsi que dans la régénération des tissus, par exemple le foie, et le système hématopoïétique.

Bibliografie

  • Field J, Fuhrman FA, Martin AW: Effect of temperature on the oxygen consumption of brain tissue. J Neurophysiol 1944; 7: 117–126. First citation in articleGoogle Scholar

  • Bing RJ, Hammond MM, et al.: The measurement of coronary blood flow, oxygen consumption, and efficiency of the left ventricle in man. Am Heart J 1949; 38: 1–24. First citation in articleGoogle Scholar

  • Fredholm BB, Linde B, Prewitt RL, Johnson PC: Oxygen-uptake and tissue oxygen-tension during adrenergic-stimulation in canine subcutaneous adipose-tissue. Acta Physiol Scand 1976; 97: 48–59. First citation in articleGoogle Scholar

  • Ziello JE, Jovin IS, Huang Y: Hypoxia-inducible factor (HIF)-1 regulatory pathway and its potential for therapeutic intervention in malignancy and ischemia. Yale J Biol Med 2007, 80: 51–60. First citation in articleGoogle Scholar

  • Jun JC, Rathore A, Younas H, Gilkes D, Polotsky VY: Hypoxia-inducible factors and cancer. Curr Sleep Med Rep 2017, 3: 1–10. First citation in articleGoogle Scholar

  • Harwood SM, Yaqoob MM, Allen DA: Caspase and calpain function in cell death: bridging the gap between apoptosis and necrosis. Ann Clin Biochem 2005; 42: 415–431. First citation in articleGoogle Scholar

  • Yuan J: Neuroprotective strategies targeting apoptotic and necrotic cell death for stroke. Apoptosis 2009; 14: 469–477. First citation in articleGoogle Scholar

  • Krijnen PA, Nijmeijer R, Meijer CJ, Visser CA, Hack CE, Niessen HW: Apoptosis in myocardial ischaemia and infarction. J Clin Pathol 2002; 55: 801–811. First citation in articleGoogle Scholar

  • Schofield CJ, Ratcliffe PJ: Oxygen sensing by HIF hydroxylases. Nat Rev Mol Cell Biol 2004; 5: 343–354. First citation in articleGoogle Scholar

  • Gorres KL, Raines RT: Prolyl 4-hydroxylase. Crit Rev Biochem Mol 2010; 45: 106–124. First citation in articleGoogle Scholar

  • Klotzsche-von Ameln A, Prade I, Grosser M, et al.: PHD4 stimulates tumor angiogenesis in osteosarcoma cells via TGF-alpha. Mol Cancer Res 2013; 11: 1337–1348. First citation in articleGoogle Scholar

  • Bruick RK, McKnight SL: A conserved family of prolyl-4-hydroxylases that modify HIF. Science 2001; 294: 1337–1340. First citation in articleGoogle Scholar

  • Jaakkola P, Mole DR, Tian YM, et al.: Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O-2-regulated prolyl hydroxylation. Science 2001; 292: 468–472. First citation in articleGoogle Scholar

  • Ratcliffe PJ: HIF-1 and HIF-2: working alone or together in hypoxia?J Clin Invest 2007; 117: 862–865. First citation in articleGoogle Scholar

  • Stroka DM, Burkhardt T, Desbaillets I, et al.: HIF-1 is expressed in normoxic tissue and displays an organ-specific regulation under systemic hypoxia. Faseb J 2001; 15: 2445–2453. First citation in articleGoogle Scholar

  • Vaupel P, Harrison L: Tumor hypoxia: Causative factors, compensatory mechanisms, and cellular response. Oncologist 2004; 9: 4–9. First citation in articleGoogle Scholar

  • Goda N, Ryan HE, Khadivi B, et al.: Hypoxia-inducible factor 1 alpha is essential for cell cycle arrest during hypoxia. Mol Cell Biol 2003; 23: 359–369. First citation in articleGoogle Scholar

  • Raval RR, Lau KW, Tran MGB, et al.: Contrasting properties of hypoxia-inducible factor 1 (HIF-1) and HIF-2 in von Hippel-Lindau-associated renal cell carcinoma. Mol Cell Biol 2005; 25: 5675–5686. First citation in articleGoogle Scholar

  • Semenza GL, Nejfelt MK, Chi SM, Antonarakis SE: Hypoxia-inducible nuclear factors bind to an enhancer element located 3’ to the human erythropoietin gene. P Natl Acad Sci USA 1991; 88: 5680–5684. First citation in articleGoogle Scholar

  • Semenza GL, Wang GL: A nuclear factor induced by hypoxia via denovo protein-synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol Cell Biol 1992; 12: 5447–5454. First citation in articleGoogle Scholar

  • Jelkmann W: Erythropoietin: structure, control of production, and function. Physiol Rev 1992; 72: 449–489. First citation in articleGoogle Scholar

  • Pugh CW, Ratcliffe PJ: Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med 2003; 9: 677–684. First citation in articleGoogle Scholar

  • Krock BL, Skuli N, Simon MC: Hypoxia-induced angiogenesis: good and evil. Genes Cancer 2011; 2: 1117–1133. First citation in articleGoogle Scholar

  • Liao D, Johnson RS: Hypoxia: a key regulator of angiogenesis in cancer. Cancer Metastasis Rev 2007; 26: 281–290. First citation in articleGoogle Scholar

  • Shaw RJ: Glucose metabolism and cancer. Curr Opin Cell Biol 2006; 18: 598–608. First citation in articleGoogle Scholar

  • Kaluz S, Kaluzova M, Liao SY, Lerman M, Stanbridge EJ: Transcriptional control of the tumor- and hypoxia-marker carbonic anhydrase 9: A one transcription factor (HIF-1) show? Bba-Rev Cancer 2009; 1795: 162–172. First citation in articleGoogle Scholar

  • Swietach P, Vaughan-Jones RD, Harris AL: Regulation of tumor pH and the role of carbonic anhydrase 9. Cancer Metast Rev 2007; 26: 299–310. First citation in articleGoogle Scholar

  • Murry CE, Jennings RB, Reimer KA: Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 1986; 74: 1124–1136. First citation in articleGoogle Scholar

  • Zhao H: Ischemic postconditioning as a novel avenue to protect against brain injury after stroke. J Cerebr Blood F Met 2009; 29: 873–885. First citation in articleGoogle Scholar

  • Thielmann M, Kottenberg E, Kleinbongard PJ, et al.: Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial. Lancet 2013; 382: 597–604. First citation in articleGoogle Scholar

  • Speechlydick ME, Mocanu MM, Yellon DM: Protein-kinase-C – Its role in ischemic preconditioning in the rat. Circ Res 1994; 75: 586–590. First citation in articleGoogle Scholar

  • Ytrehus K, Liu YG, Downey JM: Preconditioning protects ischemic tabbit heart by protein-kinase-C activation. Am J Physiol 1994; 266: H1145-H1152. First citation in articleGoogle Scholar

  • de la Barca JMC, Bakhta O, Kalakech H, et al.: Metabolic signature of remote ischemic preconditioning involving a cocktail of amino acids and biogenic amines. J Am Heart Assoc 2016; 5. pii: e003891. First citation in articleGoogle Scholar

  • Maes C, Carmeliet G, Schipani E: Hypoxia-driven pathways in bone development, regeneration and disease. Nat Rev Rheumatol 2012; 8: 358–366. First citation in articleGoogle Scholar

  • Scheid A, Wenger RH, Christina H, et al.: Hypoxia-regulated gene expression in fetal wound regeneration and adult wound repair. Pediatr Surg Int 2000; 16: 232–236. First citation in articleGoogle Scholar

  • Tandara AA, Mustoe TA: Oxygen in wound healing – More than a nutrient. World J Surg 2004; 28: 294–300. First citation in articleGoogle Scholar

  • Michalopoulos GK: Liver regeneration after partial hepatectomy: critical analysis of mechanistic dilemmas. Am J Pathol 2010; 176: 2–13. First citation in articleGoogle Scholar

  • Schadde E, Tsatsaris C, Swiderska-Syn M, et al.: Hypoxia of the growing liver accelerates regeneration. Surgery 2017; 161: 666–679. First citation in articleGoogle Scholar

  • Forristal CE, Winkler IG, Nowlan B, Barbier V, Walkinshaw G, Levesque JP: Pharmacologic stabilization of HIF-1 alpha increases hematopoietic stem cell quiescence in vivo and accelerates blood recovery after severe irradiation. Blood 2013; 121: 759–769. First citation in articleGoogle Scholar

  • Provenzano R, Besarab A, Sun CH, et al.: Oral hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) for the treatment of anemia in patients with CKD. Clin J Am Soc Nephro 2016; 11: 982–991. First citation in articleGoogle Scholar

  • Yeh TL, Leissing TM, Abboud MI, et al.: Molecular and cellular mechanisms of HIF prolyl hydroxylase inhibitors in clinical trials. Chem Sci 2017; 8: 7651–7668. First citation in articleGoogle Scholar

  • Selvaraju V, Parinandi NL, Adluri RS, et al.: Molecular mechanisms of action and therapeutic uses of pharmacological inhibitors of HIF-prolyl 4-hydroxylases for treatment of ischemic diseases. Antioxid Redox Sign 2014; 20: 2631–2665. First citation in articleGoogle Scholar