Hypoxia. 1. Intracellular sensors for oxygen and oxidative stress: novel therapeutic targets

被引:99
作者
Miyata, Toshio
Takizawa, Shunya
de Strihou, Charles van Ypersele
机构
[1] Tohoku Univ, Grad Sch Med, United Ctr Adv Res & Translat Med ART, Sendai, Miyagi 9808575, Japan
[2] Tokai Univ, Sch Med, Dept Neurol, Kanagawa 2591100, Japan
[3] Catholic Univ Louvain, Serv Nephrol, B-1200 Brussels, Belgium
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2011年 / 300卷 / 02期
关键词
oxygen sensor; hypoxia; prolylhydroxylase; hypoxia-inducible factor; nuclear factor-erythroid 2 p45-related factor 2; Kelch-like ECH-associated protein 1; TRANSCRIPTION FACTOR NRF2; INDUCIBLE FACTOR-I; SELECTIVE-INHIBITION; GENE-EXPRESSION; HIF; ISCHEMIA; DOMAIN; LOCALIZATION; ACTIVATION; MUTATION;
D O I
10.1152/ajpcell.00430.2010
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Miyata T, Takizawa S, van Ypersele de Strihou C. Intracellular sensors for oxygen and oxidative stress: novel therapeutic targets. Am J Physiol Cell Physiol 300: C226-C231, 2011. First published October 27, 2010; doi:10.1152/ajpcell.00430.2010.-A variety of human disorders, e. g., ischemic heart disease, stroke, kidney disease, eventually share the deleterious consequences of a common, hypoxic and oxidative stress pathway. In this review, we utilize recent information on the cellular defense mechanisms against hypoxia and oxidative stress with the hope to propose new therapeutic tools. The hypoxia-inducible factor (HIF) is a key player as it activates a broad range of genes protecting cells against hypoxia. Its level is determined by its degradation rate by intracellular oxygen sensors prolyl hydroxylases (PHDs). There are three different PHD isoforms (PHD1-3). Small molecule PHD inhibitors improve hypoxic injury in experimental animals but, unfortunately, may induce adverse effects associated with PHD2 inhibition, e. g., angiogenesis. As yet, no inhibitor specific for a distinct PHD isoform is currently available. Still, the specific disruption of the PHD1 gene is known to induce hypoxic tolerance, without angiogenesis and erythrocytosis, by reprogramming basal oxygen metabolism with an attendant decreased oxidative stress in hypoxic mitochondria. A specific PHD1 inhibitor might therefore offer a novel therapy against hypoxia. The nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) regulates the basal and inducible expression of numerous antioxidant stress genes. Disruption of its gene exacerbates oxidative tissue injury. Nrf2 activity is modulated by Kelch-like ECH-associated protein 1 (Keap1), an intracellular sensor for oxidative stress. Inhibitors of Keap 1 may prove therapeutic against oxidative tissue injury.
引用
收藏
页码:C226 / C231
页数:6
相关论文
共 69 条
[1]   Deficiency or inhibition of oxygen sensor Phd1 induces hypoxia tolerance by reprogramming basal metabolism [J].
Aragones, Julian ;
Schneider, Martin ;
Van Geyte, Katie ;
Fraisl, Peter ;
Dresselaers, Tom ;
Mazzone, Massimiliano ;
Dirkx, Ruud ;
Zacchigna, Serena ;
Lemieux, Helene ;
Jeoung, Nam Ho ;
Lambrechts, Diether ;
Bishop, Tammie ;
Lafuste, Peggy ;
Diez-Juan, Antonio ;
Harten, Sarah K. ;
Van Noten, Pieter ;
De Bock, Katrien ;
Willam, Carsten ;
Tjwa, Marc ;
Grosfeld, Alexandra ;
Navet, Rachel ;
Moons, Lieve ;
Vandendriessche, Thierry ;
Deroose, Christophe ;
Wijeyekoon, Bhathiya ;
Nuyts, Johan ;
Jordan, Benedicte ;
Silasi-Mansat, Robert ;
Lupu, Florea ;
Dewerchin, Mieke ;
Pugh, Chris ;
Salmon, Phil ;
Mortelmans, Luc ;
Gallez, Bernard ;
Gorus, Frans ;
Buyse, Johan ;
Sluse, Francis ;
Harris, Robert A. ;
Gnaiger, Erich ;
Hespel, Peter ;
Van Hecke, Paul ;
Schuit, Frans ;
Van Veldhoven, Paul ;
Ratcliffe, Peter ;
Baes, Myriam ;
Maxwell, Patrick ;
Carmeliet, Peter .
NATURE GENETICS, 2008, 40 (02) :170-180
[2]   Nuclear Oxygen Sensing: Induction of Endogenous Prolyl-hydroxylase 2 Activity by Hypoxia and Nitric Oxide [J].
Berchner-Pfannschmidt, Utta ;
Tug, Suzan ;
Trinidad, Buena ;
Oehme, Felix ;
Yamac, Hatice ;
Wotzlaw, Christoph ;
Flamme, Ingo ;
Fandrey, Joachim .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (46) :31745-31753
[3]   Induction of hypoxia-inducible factor-1 (HIF-1) and its target genes following focal ischaemia in rat brain [J].
Bergeron, M ;
Yu, AY ;
Solway, KE ;
Semenza, GL ;
Sharp, FR .
EUROPEAN JOURNAL OF NEUROSCIENCE, 1999, 11 (12) :4159-4170
[4]   ERYTHROPOIETIC EFFECT OF COBALT IN PATIENTS WITH OR WITHOUT ANEMIA [J].
BERK, L ;
BURCHENAL, JH ;
CASTLE, WB .
NEW ENGLAND JOURNAL OF MEDICINE, 1949, 240 (19) :754-761
[5]   Involvement of hypoxia-inducible transcription factors in polycystic kidney disease [J].
Bernhardt, Wanja Michael ;
Wiesener, Michael Sean ;
Weidemann, Alexander ;
Schmitt, Roland ;
Weichert, Wilko ;
Lechler, Philipp ;
Campean, Valentina ;
Ong, Albert Chee Meng ;
Willam, Carsten ;
Gretz, Norbert ;
Eckardt, Kai-Uwe .
AMERICAN JOURNAL OF PATHOLOGY, 2007, 170 (03) :830-842
[6]   A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth [J].
Bonnet, Sebastien ;
Archer, Stephen L. ;
Allalunis-Turner, Joan ;
Haromy, Alois ;
Beaulieu, Christian ;
Thompson, Richard ;
Lee, Christopher T. ;
Lopaschuk, Gary D. ;
Puttagunta, Lakshmi ;
Bonnet, Sandra ;
Harry, Gwyneth ;
Hashimoto, Kyoko ;
Porter, Christopher J. ;
Andrade, Miguel A. ;
Thebaud, Bernard ;
Michelakis, Evangelos D. .
CANCER CELL, 2007, 11 (01) :37-51
[7]   Effects of aging and hypoxia-inducible factor-1 activity on angiogenic cell mobilization and recovery of perfusion after limb ischemia [J].
Bosch-Marce, Marta ;
Okuyama, Hiroaki ;
Wesley, Jacob B. ;
Sarkar, Kakali ;
Kimura, Hideo ;
Liu, Ye V. ;
Zhang, Huafeng ;
Strazza, Marianne ;
Rey, Sergio ;
Savino, Lindsey ;
Zhou, Yi Fu ;
McDonald, Karin R. ;
Na, Youn ;
Vandiver, Scott ;
Rabi, Alireza ;
Shaked, Yuval ;
Kerbel, Robert ;
LaVallee, Theresa ;
Semenza, Gregg L. .
CIRCULATION RESEARCH, 2007, 101 (12) :1310-1318
[8]   Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1α during hypoxia -: A mechanism of O2 sensing [J].
Chandel, NS ;
McClintock, DS ;
Feliciano, CE ;
Wood, TM ;
Melendez, JA ;
Rodriguez, AM ;
Schumacker, PT .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (33) :25130-25138
[9]   The transcription factor NRF2 protects against pulmonary fibrosis [J].
Cho, HY ;
Reddy, SPM ;
Yamamoto, M ;
Kleeberger, SR .
FASEB JOURNAL, 2004, 18 (09) :1258-+
[10]   Role of NRF2 in protection against hyperoxic lung injury in mice [J].
Cho, HY ;
Jedlicka, AE ;
Reddy, SP ;
Kensler, TW ;
Yamamoto, M ;
Zhang, LY ;
Kleeberger, SR .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2002, 26 (02) :175-182