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Cited by 141Intracerebral and Subarachnoid Hemorrhage ResearchNeonatal and fetal brain pathologyHeme Oxygenase-1 and Carbon Monoxide

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

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Karuppagounder, Saravanan S., Alim, Ishraq, Khim, Soah J., Bourassa, Megan W., Sleiman, Sama F., John, Roseleen, Thinnes, Cyrille C., Yeh, Tzu-Lan +24 more·2016·Science Translational Medicine
DOI 10.1126/scitranslmed.aac6008PMC PMC5341138
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Abstract

Blocking oxygen-sensing prolyl hydroxylases in the rodent CNS enhances functional recovery after brain hemorrhage.

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  • Known ATF4 target genes Trib3 and Chac1 were induced by 2-DG.

    “We verified that known ATF4 target genes, Tribbles 3 (Trib3), a modulator of AKT, and Chac1, a cyclohydrolase that degrades glutathione,51”

    From 2-Deoxyglucose drives plasticity via an adaptive ER stress-ATF4 pathway and elicits stroke recovery and Alzheimer’s resilience (2023) · cites this paper as [52]

    The Results section identifies Trib3 as an ATF4-regulated gene and a negative regulator of Akt. Our copy does not establish Chac1 as an ATF4 target or report induction of either gene by 2-DG; the experiments described here use other treatments, including HCA. (LLM, conf=0.88)

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References 53 · Cited by 141

Research works printed but not linked: 46

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Authors
Karuppagounder, S. S., Alim, I., Khim, S. J., Bourassa, M. W., Sleiman, S. F., John, R., Thinnes, C. C., Yeh, T.-L., Demetriades, M., Neitemeier, S., Cruz, D., Gazaryan, I., Killilea, D. W., Morgenstern, L., Xi, G., Keep, R. F., Schallert, T., Tappero, R. V., Zhong, J., Cho, S., Maxfield, F. R., Holman, T. R., Culmsee, C., Fong, G.-H., Su, Y., Ming, G.-L., Song, H., Cave, J. W., Schofield, C. J., Colbourne, F., Coppola, G., & Ratan, R. R.
Affiliations
  • Cornell University (US)
  • University of Alberta (CA)
  • University of Oxford (GB)
  • Philipps University of Marburg (DE)
  • Children’s Hospital of Oakland, Oakland, CA 94609, USA.
  • University of Michigan (US)
  • The University of Texas at Austin (US)
  • Brookhaven National Laboratory (US)
  • University of California, Santa Cruz (US)
  • UConn Health (US)
  • Johns Hopkins University (US)
  • University of California, Los Angeles (US)
Corresponding author
Ratan, Rajiv R.
ORCID
Venue
Science Translational Medicine
Publisher
American Association for the Advancement of Science (AAAS)
Published
2016-03-02
Volume
8
Issue
328
Pages
328ra29-328ra29
ISSN
  • 1946-6234 (ISSN-L)
  • 1946-6242
DOI
10.1126/scitranslmed.aac6008
PMC
PMC5341138
OpenAlex
W2290683813
Cited by
141
References
53
Citations by year
2026: 8 · 2025: 13 · 2024: 13 · 2023: 10 · 2022: 16 · 2021: 21 · 2020: 17 · 2019: 12 · 2018: 13 · 2017: 10 · 2016: 8
FWCI
10.77
Type
journal article
Language
en
Open access
Licence
www.sciencemag.org/about/science-licenses-journal-article-reuse (vor, 365 d)
Locations
  • Science Translational Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • eScholarship (California Digital Library) (submittedVersion)
  • Open Repository and Bibliography (University of Luxembourg) (submittedVersion, cc-by-nc-sa)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
Funders
  • Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
  • Burke Foundation
  • Sperling Center for Hemorrhagic Stroke Recovery
  • New York State Department of Health Center for Research Excellence in Spinal Cord Injury (DOHC019772)
  • NIH (P01 NIA AG014930)
  • National Institute of Neurological Disorders and Stroke (P30 NS062691)
  • Welcome Trust
  • British Heart Foundation
Topics
  • Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
Keywords
intracerebral hemorrhage, HIF prolyl hydroxylase, ATF4, neuronal cell death, oxidative stress, iron chelation, blood-brain barrier permeability, functional recovery, striatum, hypoxia-inducible factor
MeSH terms
Protein Domains, Animals, Brain, Cells, Cultured, Disease Models, Animal, Gene Expression Regulation, Hemin, Iron, Iron Chelating Agents, Neurons, Oxygen, Procollagen-Proline Dioxygenase, Cell Death, Genes, Reporter, Neuroprotective Agents, Protein Isoforms, Recovery of Function, Intracranial Hemorrhages, Mice, Rats, Activating Transcription Factor 4, Hypoxia-Inducible Factor 1, alpha Subunit, Molecular Targeted Therapy

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