Evidence map›Paper›PMID 25892200›Full record

ArticleChemistry & biology2015

Hydroxamate-based histone deacetylase inhibitors can protect neurons from oxidative stress via a histone deacetylase-independent catalase-like mechanism.

David E Olson, Sama F Sleiman, Megan W Bourassa, Florence F Wagner, Jennifer P Gale, Yan-Ling Zhang, Rajiv R Ratan, Edward B Holson

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Chemistry & biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed.

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  16. The role of post-translational modifications in hearing and deafness.Cellular and molecular life sciences : CMLS · 2016
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

David E OlsonStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: dolson@broadinstitute.org.
Sama F SleimanDepartment of Natural Sciences, Lebanese American University, PO Box 36, Byblos, Lebanon.
Megan W BourassaBurke Medical Research Institute, White Plains, NY 10605, USA; Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY 10065, USA.
Florence F WagnerStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jennifer P GaleStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Yan-Ling ZhangStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Rajiv R RatanBurke Medical Research Institute, White Plains, NY 10605, USA; Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY 10065, USA.
Edward B HolsonStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: edholson@broadinstitute.org.

Funding

TRANSCRIPTIONAL RESPONSES TO MITOCHONDRIAL DYSFUNCTIONP01AG014930 · NIA · WINIFRED MASTERSON BURKE MED RES INST · PI STARKOV, ANATOLY A · 1999 to 2020
$30.7M
NIA NIH HHS P01 AG014930
6 · The paper itself

Abstract

Histone deacetylase (HDAC) inhibitors have shown enormous promise for treating various disease states, presumably due to their ability to modulate acetylation of histone and non-histone proteins. Many of these inhibitors contain functional groups capable of strongly chelating metal ions. We demonstrate that several members of one such class of compounds, the hydroxamate-based HDAC inhibitors, can protect neurons from oxidative stress via an HDAC-independent mechanism. This previously unappreciated antioxidant mechanism involves the in situ formation of hydroxamate-iron complexes that catalyze the decomposition of hydrogen peroxide in a manner reminiscent of catalase. We demonstrate that while many hydroxamate-containing HDAC inhibitors display a propensity for binding iron, only a subset form active catalase mimetics capable of protecting neurons from exogenous H2O2. In addition to their impact on stroke and neurodegenerative disease research, these results highlight the possibility that HDAC-independent factors might play a role in the therapeutic effects of hydroxamate-based HDAC inhibitors.

Indexed as

AnimalsCatalaseCoordination ComplexesHistone Deacetylase InhibitorsHistone DeacetylasesHydrogen PeroxideHydroxamic AcidsIronMiceNeuronsNeuroprotective AgentsOxidative StressProtein BindingReactive Oxygen SpeciesCatalaseCoordination ComplexesFenton's reagentHistone Deacetylase InhibitorsHistone DeacetylasesHydrogen PeroxideHydroxamic AcidsIronNeuroprotective AgentsReactive Oxygen Species

Identifiers

PMID25892200
PMCPMC4562013

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.