Abstract
Acetazolamide has been recognized as an effective treatment for acute mountain sickness. The efficacy of acetazolamide is related to metabolic acidosis, which promotes chemoreceptors to respond to hypoxic stimuli at altitude. In this study, adult male Sprague-Dawley rats were treated with acetazolamide (100mg/kg or 50mg/kg, I.P.) for 3 days. Primary cultured cortical neurons and PC12 cell lines were exposed to acidosis-permissive (pH 6.5) or standard (pH 7.2) media for 20h. HIF-1alpha and its target genes were assayed by Western blot, real-time PCR, HIF-1 DNA-binding assay and chloramphenicol acetyltransferase reporter gene assay. HIF-1alpha protein level and HIF-1 DNA-binding activities were increased in cerebral cortices of rats treated with acetazolamide. Moreover, the mRNA levels of erythropoietin, vascular endothelial growth factor, and glucose transporter-1 also increased. The HIF-1alpha protein level and activity of HIF-driven chloramphenicol acetyltransferase reporters of cortical neurons and PC12 cells treated with acidosis media were significantly enhanced. We conclude that the normoxic induction of HIF-1alpha and HIF-1 mediated genes by acetazolamide may mediate the effect of acetazolamide in the reduction of symptom...Continue Reading
References
Aug 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·M S GhandourW S Sly
Jan 8, 1990·Brain Research·G C Tombaugh, R M Sapolsky
Oct 1, 1985·Archives of Internal Medicine·I HellerE Theodor
Jun 4, 1993·Science·D A KakuD W Choi
May 1, 1997·Critical Care Medicine·Y MorimotoE S Alojado
Jan 7, 1999·The European Respiratory Journal·E R Swenson
Aug 29, 2001·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·N M Jones, M Bergeron
Oct 2, 2001·The Journal of Physiology·O B NielsenK Overgaard
Oct 13, 2001·Science·R K Bruick, S L McKnight
Sep 5, 2002·Nature Reviews. Cancer·William G Kaelin
Jun 8, 2004·Nature Cell Biology·Karim MekhailStephen Lee
Aug 10, 2004·The Journal of Experimental Biology·Hugo H Marti
Jun 23, 2007·The Journal of Physiology·Jorge SolizVincent Joseph
Oct 11, 2007·Science's STKE : Signal Transduction Knowledge Environment·Gregg L Semenza
Citations
Jan 13, 2012·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Vien Khach LaiHusnain Kh Haider
Dec 17, 2009·Cardiovascular Research·Roberta MelchionnaMonica Napolitano
Mar 22, 2014·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Akiko SuzukiKen Okumura
Mar 15, 2014·Molecular Neurobiology·Li ZhaoRui-Yun Peng
Jan 29, 2011·Biomaterials·Lirija AliliPeter Brenneisen
May 23, 2015·Military Medical Research·Yan-Hui HaoRui-Yun Peng
Mar 21, 2015·BioMed Research International·Emanuele SassoNicola Zambrano
Feb 16, 2010·Journal of Neuroscience Research·Chunhua ChenJohn H Zhang
Sep 4, 2015·The Journal of Pharmacology and Experimental Therapeutics·Mohamed BejaouiJoan Rosselló-Catafau
Aug 29, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shih-Hung TsaiShing-Jong Lin
May 22, 2020·Current Eye Research·Xi HanYang Liu
Aug 22, 2015·Journal of Applied Physiology·Erik R Swenson
Jan 5, 2019·Cancer Metastasis Reviews·Oliver Thews, Anne Riemann
Jun 26, 2013·Journal of Chemical Information and Modeling·Mahesh Kumar Teli, Rajanikant G K
Aug 27, 2021·Neural Plasticity·Yanping WangShuxia Qian