Baicalein induces functional hypoxia-inducible factor-1alpha and angiogenesis

Molecular Pharmacology
Hyunju ChoEun Gyeong Yang

Abstract

Targeting the oxygen-sensing mechanisms of the hypoxiainducible factor (HIF) pathway provides pharmacological ways of manipulating the HIF response. Because HIF-1alpha-specific prolyl-4 hydroxylases (PHDs) prime degradation of HIF-1alpha, we have made an effort to find a small molecule capable of up-regulating the HIF pathway by inhibiting prolyl hydroxylation. Through an in vitro high-throughput screen, we have discovered a PHD2 inhibitor baicalein, which is also found to abrogate asparaginyl hydroxylation of HIF-1alpha. Such inhibitory effects are reversed by the addition of excess 2-oxoglutarate and iron(II), suggesting the involvement of baicalein's binding at the enzyme active sites, which has also been corroborated by spectroscopic binding assays between baicalein and enzyme. In addition, baicalein suppresses ubiquitination of HIF-1alpha, which works in concert with the inhibition of the HIF-specific hydroxylases to increase the HIF-1alpha content, leading to induction of HIF-1-mediated reporter gene activity and target gene transcription in tissue culture cells, whereas it induces HIF-independent activation of other genes. Furthermore, in vivo organ models based on the chick chorioallantoic membrane assay demonstrate tha...Continue Reading

References

Mar 31, 2000·Nature Medicine·P Carmeliet
Mar 13, 2001·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Z GaoH Xu
Aug 4, 2001·Cancer Letters·K IguraK Kaji
Oct 13, 2001·Science·R K Bruick, S L McKnight
Apr 24, 2002·Seminars in Cell & Developmental Biology·Patrick H Maxwell, Peter J Ratcliffe
Sep 28, 2002·Proceedings of the National Academy of Sciences of the United States of America·Mircea IvanWilliam G Kaelin
Nov 15, 2002·Proceedings of the National Academy of Sciences of the United States of America·Charles E DannJohann Deisenhofer
Nov 26, 2002·The Journal of Biological Chemistry·Jonathan M ElkinsChristopher J Schofield
Feb 21, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Tobias LindenRoland H Wenger
Mar 26, 2003·European Journal of Pharmacology·Yuh-Chiang ShenChieh-Fu Chen
Jun 5, 2003·Nature Medicine·Christopher W Pugh, Peter J Ratcliffe
Jun 6, 2003·The Journal of Biological Chemistry·Maija HirsiläJohanna Myllyharju
Jul 8, 2003·International Journal of Cancer. Journal International Du Cancer·Jun-Jen LiuFung-Jou Lu
Aug 12, 2004·Physiology·Gregg L Semenza
May 26, 2005·Journal of the American Chemical Society·Michael A McDonoughChristopher J Schofield
Aug 13, 2005·Advances in Genetics·Pinak B Shah, Douglas W Losordo
Sep 6, 2005·Biochemical and Biophysical Research Communications·Charles E Dann, Richard K Bruick
Sep 27, 2005·Biochemical and Biophysical Research Communications·Hyunju ChoEun Gyeong Yang
Oct 18, 2005·The Journal of Biological Chemistry·Ambreena SiddiqRajiv R Ratan
Dec 16, 2005·Nature·Napoleone Ferrara, Robert S Kerbel
Apr 28, 2006·The Journal of Biological Chemistry·Daotai NieKenneth V Honn
Jun 20, 2006·Proceedings of the National Academy of Sciences of the United States of America·Michael A McDonoughChristopher J Schofield
Aug 2, 2006·Molecular BioSystems·Luke A McNeillChristopher J Schofield
Sep 12, 2006·Bioorganic & Medicinal Chemistry Letters·Namal C WarshakoonMarlene Mekel
Nov 15, 2006·Biochemical Pharmacology·M Christiane Brahimi-Horn, Jacques Pouysségur
Feb 27, 2007·The Journal of Pathology·T MurakamiT Kishida

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Citations

Feb 2, 2012·The British Journal of Radiology·M I Koukourakis
Nov 28, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·So Yeon Kim, Eun Gyeong Yang
Mar 4, 2009·Cell Biology International·Wen-Bin LiBing-Jun Shi
Aug 23, 2016·The Journal of Clinical Investigation·Monica M Olcina, Amato J Giaccia
Apr 27, 2013·Biochemical and Biophysical Research Communications·Yu-Ran NaEun Gyeong Yang
Mar 16, 2017·Biochemical and Biophysical Research Communications·Hyunju KimEun Gyeong Yang
May 18, 2010·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Young-Suk ChoJong-Wan Park
Apr 2, 2009·Organogenesis·Lauren S SefcikEdward A Botchwey
Dec 23, 2016·Medicinal Chemistry Research : an International Journal for Rapid Communications on Design and Mechanisms of Action of Biologically Active Agents·Ying GaoYi Charlie Chen
Jan 23, 2010·Molecular BioSystems·Masaaki SakuraiAnton Simeonov
Feb 18, 2011·Fundamental & Clinical Pharmacology·Chandrashekar NaveenkumarThiruvengadam Devaki
Aug 19, 2015·Journal of Cellular Biochemistry·Hyunju KimEun Gyeong Yang
Mar 11, 2011·Chemical Society Reviews·Nathan R RoseChristopher J Schofield
May 26, 2020·Tissue Engineering and Regenerative Medicine·Ahmed G Abu-ShahbaBettina Mannerström
Jan 15, 2021·International Journal of Molecular Sciences·Zdeněk KejíkMilan Jakubek

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