Therapeutic targeting of oxygen-sensing prolyl hydroxylases abrogates ATF4-dependent neuronal death and improves outcomes after brain hemorrhage in several rodent models

Science Translational Medicine

Volumn 8, Issue 328, 2016, Pages

  Karuppagounder, Saravanan S ^a,b   Alim, Ishraq ^a,b   Khim, Soah J ^a,b   Bourassa, Megan W ^a,b   Sleiman, Sama F ^a,b   John, Roseleen ^c   Thinnes, Cyrille C ^d   Yeh, Tzu Lan ^d   Demetriades, Marina ^d   Neitemeier, Sandra ^e   Cruz, Dana ^f   Gazaryan, Irina ^a,b   Killilea, David W ^g   Morgenstern, Lewis ^h   Xi, Guohua ^h   Keep, Richard F ^h   Schallert, Timothy ⁱ   Tappero, Ryan V ^j   Zhong, Jian ^a,b   Cho, Sunghee ^a,b   Maxfield, Frederick R ^f   Holman, Theodore R ^k   Culmsee, Carsten ^e   Fong, Guo Hua ^l   Su, Yijing ^m   Ming, Guo Li ^m   Song, Hongjun ^m   Cave, John W ^a,b   Schofield, Christopher J ^d   Colbourne, Frederick ^c   Coppola, Giovanni ⁿ   Ratan, Rajiv R ^a,b   more..

^a BURKE MEDICAL RESEARCH INSTITUTE   (United States)

^b FEIL FAMILY BRAIN AND MIND RESEARCH INSTITUTE   (United States)

^c UNIVERSITY OF ALBERTA   (Canada)

^d UNIVERSITY OF OXFORD   (United Kingdom)

^e PHILIPPS UNIVERSITY MARBURG   (Germany)

^f WEILL CORNELL MEDICAL COLLEGE   (United States)

^g CHILDREN S HOSPITAL OAKLAND   (United States)

^h UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

ⁱ UNIVERSITY OF TEXAS AT AUSTIN   (United States)

^j BROOKHAVEN NATIONAL LABORATORY   (United States)

^k UNIVERSITY OF CALIFORNIA   (United States)

^l UNIVERSITY OF CONNECTICUT HEALTH CENTER   (United States)

^m JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

ⁿ UNIVERSITY OF CALIFORNIA   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR 4; ADAPTAQUIN; HYPOXIA INDUCIBLE FACTOR; HYPOXIA INDUCIBLE FACTOR PROLINE DIOXYGENASE; HYPOXIA INDUCIBLE FACTOR PROLYL HYDROXYLASE INHIBITOR; IRON; UNCLASSIFIED DRUG; ZINC; HEMIN; HYPOXIA INDUCIBLE FACTOR 1ALPHA; IRON CHELATING AGENT; ISOPROTEIN; NEUROPROTECTIVE AGENT; OXYGEN; PROCOLLAGEN PROLINE 2 OXOGLUTARATE 4 DIOXYGENASE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BEHAVIOR DISORDER; BRAIN HEMORRHAGE; BRAIN LEVEL; CONTROLLED STUDY; CORPUS STRIATUM; DRUG TARGETING; EMBRYO; IN VITRO STUDY; IN VIVO STUDY; MALE; MOUSE; NERVE CELL NECROSIS; NONHUMAN; OUTCOME ASSESSMENT; OXIDATIVE STRESS; PRIORITY JOURNAL; RAT; ANIMAL; ANTAGONISTS AND INHIBITORS; BRAIN; CELL CULTURE; CELL DEATH; CHEMISTRY; CONVALESCENCE; DISEASE MODEL; DRUG EFFECTS; GENE EXPRESSION REGULATION; METABOLISM; MOLECULARLY TARGETED THERAPY; NERVE CELL; PATHOLOGY; PATHOPHYSIOLOGY; PROTEIN DOMAIN; REPORTER GENE;

ACTIVATING TRANSCRIPTION FACTOR 4; ANIMALS; BRAIN; CELL DEATH; CELLS, CULTURED; DISEASE MODELS, ANIMAL; GENE EXPRESSION REGULATION; GENES, REPORTER; HEMIN; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; INTRACRANIAL HEMORRHAGES; IRON; IRON CHELATING AGENTS; MICE; MOLECULAR TARGETED THERAPY; NEURONS; NEUROPROTECTIVE AGENTS; OXYGEN; PROCOLLAGEN-PROLINE DIOXYGENASE; PROTEIN DOMAINS; PROTEIN ISOFORMS; RATS; RECOVERY OF FUNCTION;

EID: 84959459175     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.aac6008     Document Type: Article

References (52)

1. R. F. Keep, Y. Hua, G. Xi, Intracerebral haemorrhage: Mechanisms of injury and therapeutic targets. Lancet Neurol. 11, 720-731 (2012).
2. M. E. Gurol, S. M. Greenberg, Management of intracerebral hemorrhage. Curr. Atheroscler. Rep. 10, 324-331 (2008).
3. M. A. Greenough, J. Camakaris, A. I. Bush, Metal dyshomeostasis and oxidative stress in Alzheimer's disease. Neurochem. Int. 62, 540-555 (2013).
4. H. H. Andersen, K. B. Johnsen, T. Moos, Iron deposits in the chronically inflamed central nervous system and contributes to neurodegeneration. Cell. Mol. Life Sci. 71, 1607-1622 (2014).
5. L. M. Warkentin, A. M. Auriat, S. Wowk, F. Colbourne, Failure of deferoxamine, an iron chelator, to improve outcome after collagenase-induced intracerebral hemorrhage in rats. Brain Res. 1309, 95-103 (2010).
6. D. L. Lee, F. G. Strathmann, R. Gelein, J. Walton, M. Mayer-Pröschel, Iron deficiency disrupts axon maturation of the developing auditory nerve. J. Neurosci. 32, 5010-5015 (2012).
7. S. S. Karuppagounder, R. R. Ratan, Hypoxia-inducible factor prolyl hydroxylase inhibition: Robust new target or another big bust for stroke therapeutics? J.Cereb. Blood Flow Metab. 32, 1347-1361 (2012).
8. M. B. H. Youdim, L. Kupershmidt, T. Amit, O. Weinreb, Promises of novel multi-target neuroprotective and neurorestorative drugs for Parkinson's disease. Parkinsonism Relat. Disord. 20 (Suppl. 1), S132-S136 (2014).
9. A. Ozer, R. K. Bruick, Non-heme dioxygenases: Cellular sensors and regulators jelly rolled into one? Nat. Chem. Biol. 3, 144-153 (2007).
10. W. G. Kaelin Jr., P. J. Ratcliffe, Oxygen sensing by metazoans: The central role of the HIF hydroxylase pathway. Mol. Cell 30, 393-402 (2008).
11. A. Siddiq, I. A. Ayoub, J. C. Chavez, L. Aminova, S. Shah, J. C. LaManna, S. M. Patton, J. R. Connor, R. A. Cherny, I. Volitakis, A. I. Bush, I. Langsetmo, T. Seeley, V. Gunzler, R. R. Ratan, Hypoxiainducible factor prolyl 4-hydroxylase inhibition. A target for neuroprotection in the central nervous system. J. Biol. Chem. 280, 41732-41743 (2005).
12. A. Siddiq, L. R. Aminova, C. M. Troy, K. Suh, Z. Messer, G. L. Semenza, R. R. Ratan, Selective inhibition of hypoxia-inducible factor (HIF) prolyl-hydroxylase 1 mediates neuroprotection against normoxic oxidative death via HIF-and CREB-independent pathways. J. Neurosci. 29, 8828-8838 (2009).
13. R. Kunze, W. Zhou, R. Veltkamp, B. Wielockx, G. Breier, H. H. Marti, Neuron-specific prolyl-4-hydroxylase domain 2 knockout reduces brain injury after transient cerebral ischemia. Stroke 43, 2748-2756 (2012).
14. R.-L. Chen, S. Nagel, M. Papadakis, T. Bishop, P. Pollard, P. J. Ratcliffe, C. W. Pugh, A. M. Buchan, Roles of individual prolyl-4-hydroxylase isoforms in the first 24 hours following transient focal cerebral ischaemia: Insights from genetically modified mice. J. Physiol. 590, 4079-4091 (2012).
15. T. N. Dang, S. R. Robinson, R. Dringen, G. M. Bishop, Uptake, metabolism and toxicity of hemin in cultured neurons. Neurochem. Intl. 58, 804-811 (2011).
16. J. Chen-Roetling, Y. Cai, X. Lu, R. F. Regan, Hemin uptake and release by neurons and glia. Free Rad. Res. 48, 200-205 (2014).
17. A. N. Higdon, G. A. Benavides, B. K. Chacko, X. Ouyang, M. S. Johnson, A. Landar, J. Zhang, V. M. Darley-Usmar, Hemin causes mitochondrial dysfunction in endothelial cells through promoting lipid peroxidation: The protective role of autophagy. Am. J. Physiol. Heart Circ. Physiol. 302, H1394-H1409 (2012).
18. J. Aragonés, P. Fraisl, M. Baes, P. Carmeliet, Oxygen sensors at the crossroad of metabolism. Cell Metab. 9, 11-22 (2009).
19. Y. A. Minamishima, W. G. Kaelin Jr., Reactivation of hepatic EPO synthesis in mice after PHD loss. Science 329, 407 (2010).
20. J. C. Chavez, O. Baranova, J. Lin, P. Pichiule, The transcriptional activator hypoxia inducible factor 2 (HIF-2/EPAS-1) regulates the oxygen-dependent expression of erythropoietin in cortical astrocytes. J. Neurosci. 26, 9471-9481 (2006).
21. M. Safran, W. Y. Kim, F. O'Connell, L. Flippin, V. Günzler, J. W. Horner, R. A. DePinho, W. G. Kaelin Jr., Mouse model for noninvasive imaging of HIF prolyl hydroxylase activity: Assessment of an oral agent that stimulates erythropoietin production. Proc. Natl. Acad. Sci. U.S.A. 103, 105-110 (2006).
22. N. A. Smirnova, I. Rakhman, N. Moroz, M. Basso, J. Payappilly, S. Kazakov, F. Hernandez-Guzman, I. N. Gaisina, A. P. Kozikowski, R. R. Ratan, I. G. Gazaryan, Utilization of an in vivo reporter for high throughput identification of branched small molecule regulators of hypoxic adaptation. Chem. Biol. 17, 380-391 (2010).
23. Y. Hua, T. Schallert, R. F. Keep, J. Wu, J. T. Hoff, G. Xi, Behavioral tests after intracerebral hemorrhage in the rat. Stroke 33, 2478-2484 (2002).
24. C. L. MacLellan, R. Paquette, F. Colbourne, A critical appraisal of experimental intracerebral hemorrhage research. J. Cereb. Blood Flow Metab. 32, 612-627 (2012).
25. G. L. Semenza, HIF-1, O2, and the 3 PHDs: How animal cells signal hypoxia to the nucleus. Cell 107, 1-3 (2001).
26. L. R. Aminova, J. C. Chavez, J. Lee, H. Ryu, A. Kung, J. C. LaManna, R. R. Ratan, Prosurvival and prodeath effects of hypoxia-inducible factor-1a stabilization in a murine hippocampal cell line. J. Biol. Chem. 280, 3996-4003 (2005).
27. P. S. Lange, J. C. Chavez, J. T. Pinto, G. Coppola, C.-W. Sun, T. M. Townes, D. H. Geschwind, R. R. Ratan, ATF4 is an oxidative stress-inducible, prodeath transcription factor in neurons in vitro and in vivo. J. Exp. Med. 205, 1227-1242 (2008).
28. J. Schödel, S. Oikonomopoulos, J. Ragoussis, C. W. Pugh, P. J. Ratcliffe, D. R. Mole, Highresolution genome-widemapping of HIF-binding sites by ChIP-seq. Blood 117, e207-e217 (2011).
29. K. Du, S. Herzig, R. N. Kulkarni, M. Montminy, TRB3: A tribbles homolog that inhibits Akt/PKB activation by insulin in liver. Science 300, 1574-1577 (2003).
30. N. Zareen, S. C. Biswas, L. A. Greene, A feed-forward loop involving Trib3, Akt and FoxO mediates death of NGF-deprived neurons. Cell Death Differ. 20, 1719-1730 (2013).
31. G. Qing, B. Li, A. Vu, N. Skuli, Z. E. Walton, X. Liu, P. A. Mayes, D. R. Wise, C. B. Thompson, J. M. Maris, M. D. Hogarty, M. C. Simon, ATF4 regulates MYC-mediated neuroblastoma cell death upon glutamine deprivation. Cancer Cell 22, 631-644 (2012).
32. C. W. Liew, J. Bochenski, D. Kawamori, J. Hu, C. A. Leech, K. Wanic, M. Malecki, J. H. Warram, L. Qi, A. S. Krolewski, R. N. Kulkarni, The pseudokinase tribbles homolog 3 interacts with ATF4 to negatively regulate insulin exocytosis in human and mouse b cells. J. Clin. Invest. 120, 2876-2888 (2010).
33. J. Köditz, J. Nesper, M. Wottawa, D. P. Stiehl, G. Camenisch, C. Franke, J. Myllyharju, R. H. Wenger, D. M. Katschinski, Oxygen-dependent ATF-4 stability is mediated by the PHD3 oxygen sensor. Blood 110, 3610-3617 (2007).
34. H. Ryu, J. Lee, B. A. Olofsson, A. Mwidau, A. Dedeoglu, M. Escudero, E. Flemington, J. Azizkhan-Clifford, R. J. Ferrante, R. R. Ratan, Histone deacetylase inhibitors prevent oxidative neuronal death independent of expanded polyglutamine repeats via an Sp1-dependent pathway. Proc. Natl. Acad. Sci. U.S.A. 100, 4281-4286 (2003).
35. K. Van Leyen, T. R. Holman, D. J. Maloney, The potential of 12/15-lipoxygenase inhibitors in stroke therapy. Future Med. Chem. 6, 1853-1855 (2014).
36. P. A. Adlard, R. A. Cherny, D. I. Finkelstein, E. Gautier, E. Robb, M. Cortes, I. Volitakis, X. Liu, J. P. Smith, K. Perez, K. Laughton, Q.-X. Li, S. A. Charman, J. A. Nicolazzo, S. Wilkins, K. Deleva, T. Lynch, G. Kok, C. W. Ritchie, R. E. Tanzi, R. Cappai, C. L. Masters, K. J. Barnham, A. I. Bush, Rapid restoration of cognition in Alzheimer's transgenic mice with 8-hydroxy quinoline analogs is associated with decreased interstitial Ab. Neuron 59, 43-55 (2008).
37. D. F. Tardiff, M. L. Tucci, K. A. Caldwell, G. A. Caldwell, S. Lindquist, Different 8-hydroxyquinolines protect models of TDP-43 protein, a-synuclein, and polyglutamine proteotoxicity through distinct mechanisms. J. Biol. Chem. 287, 4107-4120 (2012).
38. N. G. Faux, C. W. Ritchie, A. Gunn, A. Rembach, A. Tsatsanis, J. Bedo, J. Harrison, L. Lannfelt, K. Blennow, H. Zetterberg, M. Ingelsson, C. L. Masters, R. E. Tanzi, J. L. Cummings, C. M. Herd, A. I. Bush, PBT2 rapidly improves cognition in Alzheimer's Disease: Additional phase II analyses. J. Alz. Dis. 20, 509-516 (2010).
39. B. W. Wong, A. Kuchnio, U. Bruning, P. Carmeliet, Emerging novel functions of the oxygensensing prolyl hydroxylase domain enzymes. Trends Biochem. Sci. 38, 3-11 (2013).
40. W. Luo, H. Hu, R. Chang, J. Zhong, M. Knabel, R. O'Meally, R. N. Cole, A. Pandey, G. L. Semenza, Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1. Cell 145, 732-744 (2011).
41. S. C. Landis, S. G. Amara, K. Asadullah, C. P. Austin, R. Blumenstein, E. W. Bradley, R. G. Crystal, R. B. Darnell, R. J. Ferrante, H. Fillit, R. Finkelstein, M. Fisher, H. E. Gendelman, R. M. Golub, J. L. Goudreau, R. A. Gross, A. K. Gubitz, S. E. Hesterlee, D. W. Howells, J. Huguenard, K. Kelner, W. Koroshetz, D. Krainc, S. E. Lazic, M. S. Levine, M. R. Macleod, J. M. McCall, R. T. Moxley III, K. Narasimhan, L. J. Noble, S. Perrin, J. D. Porter, O. Steward, E. Unger, U. Utz, S. D. Silberberg, A call for transparent reporting to optimize the predictive value of preclinical research. Nature 490, 187-191 (2012).
42. K. Takeda, V. C. Ho, H. Takeda, L.-J. Duan, A. Nagy, G.-H. Fong, Placental but not heart defects are associated with elevated hypoxia-inducible factor a levels in mice lacking prolyl hydroxylase domain protein 2. Mol. Cell. Biol. 26, 8336-8346 (2006).
43. M. A. Rynkowski, G. H. Kim, R. J. Komotar, M. L. Otten, A. F. Ducruet, B. E. Zacharia, C. P. Kellner, D. K. Hahn, M. B. Merkow, M. C. Garrett, R. M. Starke, B.-M. Cho, S. A. Sosunov, E. S. Connolly, A mouse model of intracerebral hemorrhage using autologous blood infusion. Nat. Protoc. 3, 122-128 (2008).
44. M. Grossetete, G. A. Rosenberg, Tissue inhibitor of matrix metalloproteinases-3 (TIMP-3) lacks involvement in bacterial collagenase-induced intracerebral hemorrhage in mouse. Acta Neurochir. Suppl. 105, 89-93 (2008).
45. J. Tang, J. Liu, C. Zhou, J. S. Alexander, A. Nanda, D. N. Granger, J. H. Zhang, Mmp-9 deficiency enhances collagenase-induced intracerebral hemorrhage and brain injury in mutant mice. J. Cereb. Blood Flow Metab. 24, 1133-1145 (2004).
46. J. Wang, J. Fields, C. Zhao, J. Langer, R. K. Thimmulappa, T. W. Kensler, M. Yamamoto, S. Biswal, S. Doré, Role of Nrf2 in protection against intracerebral hemorrhage injury in mice. Free Rad. Biol. Med. 43, 408-414 (2007).
47. J. Wang, H. Zhuang, S. Doré, Heme oxygenase 2 is neuroprotective against intracerebral hemorrhage. Neurobiol. Dis. 22, 473-476 (2006).
48. P. R. Krafft, D. W. McBride, T. Lekic, W. B. Rolland, C. E. Mansell, Q. Ma, J. Tang, J. H. Zhang, Correlation between subacute sensorimotor deficits and brain edema in two mouse models of intracerebral hemorrhage. Behav. Brain Res. 264, 151-160 (2014).
49. X. Zhao, G. Sun, J. Zhang, R. Strong, P. K. Dash, Y. W. Kan, J. C. Grotta, J. Aronowski, Transcription factor Nrf2 protects the brain from damage produced by intracerebral hemorrhage. Stroke 38, 3280-3286 (2007).
50. T. Schallert, S. M. Fleming, J. L. Leasure, J. L. Tillerson, S. T. Bland, CNS plasticity and assessment of forelimb sensorimotor outcome in unilateral rat models of stroke, cortical ablation, parkinsonism and spinal cord injury. Neuropharmacology 39, 777-787 (2000).
51. R. Chowdhury, K. K. Yeoh, Y.-M. Tian, L. Hillringhaus, E. A. Bagg, N. R. Rose, I. K. H. Leung, X. S. Li, E. C. Y. Woon, M. Yang, M. A. McDonough, O. N. King, I. J. Clifton, R. J. Klose, T. D. W Claridge, P. J. Ratcliffe, C. J. Schofield, A. Kawamura, The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases. EMBO Rep. 12, 463-469 (2011).
52. O. Baranova, L. F. Miranda, P. Pichiule, I. Dragatsis, R. S. Johnson, J. C. Chavez, Neuronspecific inactivation of the hypoxia inducible factor 1a increases brain injury in a mouse model of transient focal cerebral ischemia. J. Neurosci. 27, 6320-6332 (2007).