Evidence map›Paper›PMID 30890112›Full record

ArticleStroke2019

Mitophagy Reduces Oxidative Stress Via Keap1 (Kelch-Like Epichlorohydrin-Associated Protein 1)/Nrf2 (Nuclear Factor-E2-Related Factor 2)/PHB2 (Prohibitin 2) Pathway After Subarachnoid Hemorrhage in Rats.

Tongyu Zhang, Pei Wu, Enkhjargal Budbazar, Qiquan Zhu, Chengmei Sun, Jun Mo, Jianhua Peng, Vadim Gospodarev, Jiping Tang, Huaizhang Shi and 1 more

Expression of concernErratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stroke, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 93 papers.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed
12.7field-weighted citation impact, top 1% of its field
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

93 citing papers in PubMed, 167 citations in OpenAlex.

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  18. Apigenin Ameliorates HPharmaceuticals (Basel, Switzerland) · 2024
    Article
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  20. Article

33 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Tongyu ZhangFrom the Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China (T.Z., P.W., H.S.).
Pei WuFrom the Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China (T.Z., P.W., H.S.).
Enkhjargal BudbazarDepartment of Physiology and Pharmacology, Loma Linda University, CA (T.Z., P.W., E.B., Q.Z., C.S., J.M., J.P., V.G., J.T., J.H.Z.).
Qiquan ZhuDepartment of Physiology and Pharmacology, Loma Linda University, CA (T.Z., P.W., E.B., Q.Z., C.S., J.M., J.P., V.G., J.T., J.H.Z.).
Chengmei SunDepartment of Physiology and Pharmacology, Loma Linda University, CA (T.Z., P.W., E.B., Q.Z., C.S., J.M., J.P., V.G., J.T., J.H.Z.).
Jun MoDepartment of Physiology and Pharmacology, Loma Linda University, CA (T.Z., P.W., E.B., Q.Z., C.S., J.M., J.P., V.G., J.T., J.H.Z.).
Jianhua PengDepartment of Physiology and Pharmacology, Loma Linda University, CA (T.Z., P.W., E.B., Q.Z., C.S., J.M., J.P., V.G., J.T., J.H.Z.).
Vadim GospodarevDepartment of Physiology and Pharmacology, Loma Linda University, CA (T.Z., P.W., E.B., Q.Z., C.S., J.M., J.P., V.G., J.T., J.H.Z.).
Jiping TangDepartment of Physiology and Pharmacology, Loma Linda University, CA (T.Z., P.W., E.B., Q.Z., C.S., J.M., J.P., V.G., J.T., J.H.Z.).
Huaizhang ShiFrom the Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China (T.Z., P.W., H.S.).
John H ZhangDepartment of Physiology and Pharmacology, Loma Linda University, CA (T.Z., P.W., E.B., Q.Z., C.S., J.M., J.P., V.G., J.T., J.H.Z.).
First Affiliated Hospital of Harbin Medical University · CNHarbin Medical University · CN

Funding

Vascular Biology Core FacilityP01NS082184 · NINDS · LOMA LINDA UNIVERSITY · PI PEARCE, WILLIAM J. · 2014 to 2018
$6.1M
Neurovascular Protection for Early Brain Injury after SAHR01NS081740 · NINDS · LOMA LINDA UNIVERSITY · PI ZHANG, JOHN H · 2013 to 2017
$1.6M
NINDS NIH HHS P01 NS082184NINDS NIH HHS R01 NS081740
6 · The paper itself

Abstract

Background and Purpose- Mitoquinone has been reported as a mitochondria-targeting antioxidant to promote mitophagy in various chronic diseases. Here, our aim was to study the role of mitoquinone in mitophagy activation and oxidative stress-induced neuronal death reduction after subarachnoid hemorrhage (SAH) in rats. Methods- Endovascular perforation was used for SAH model of male Sprague-Dawley rats. Exogenous mitoquinone was injected intraperitoneally 1 hour after SAH. ML385, an inhibitor of Nrf2 (nuclear factor-E2-related factor 2), was given intracerebroventricularly 24 hours before SAH. Small interfering RNA for PHB2 (prohibitin 2) was injected intracerebroventricularly 48 hours before SAH. Nuclear, mitochondrial, and cytoplasmic fractions were gathered using nucleus and mitochondria isolation kits. SAH grade evaluation, short- and long- term neurological function tests, oxidative stress, and apoptosis measurements were performed. Pathway related proteins were investigated with Western blot and immunofluorescence staining. Results- Expression of Keap1 (Kelch-like epichlorohydrin-associated protein 1, 2.84× at 24 hours), Nrf2 (2.78× at 3 hours), and LC3II (light chain 3-II; 1.94× at 24 hours) increased, whereas PHB2 (0.46× at 24 hours) decreased after SAH compared with sham group. Mitoquinone treatment attenuated oxidative stress and neuronal death, both short-term and long-term. Administration of mitoquinone resulted in a decrease in expression of Keap1 (0.33×), Romo1 (reactive oxygen species modulator 1; 0.24×), Bax (B-cell lymphoma-2 associated X protein; 0.31×), Cleaved Caspase-3 (0.29×) and an increase in Nrf2 (2.13×), Bcl-xl (B-cell lymphoma-extra large; 1.67×), PINK1 (phosphatase and tensin-induced kinase 1; 1.67×), Parkin (1.49×), PHB2 (1.60×), and LC3II (1.67×) proteins compared with SAH+vehicle group. ML385 abolished the treatment effects of mitoquinone on behavior and protein levels. PHB2 small interfering RNA reversed the outcomes of mitoquinone administration through reduction in protein expressions downstream of PHB2. Conclusions- Mitoquinone inhibited oxidative stress-related neuronal death by activating mitophagy via Keap1/Nrf2/PHB2 pathway after SAH. Mitoquinone may serve as a potential treatment to relieve brain injury after SAH.

Indexed as

AnimalsApoptosisKelch-Like ECH-Associated Protein 1MaleMitophagyNF-E2-Related Factor 2Organophosphorus CompoundsOxidative StressRatsRats, Sprague-DawleyRepressor ProteinsSignal TransductionSubarachnoid HemorrhageUbiquinoneKelch-Like ECH-Associated Protein 1mitoquinoneNfe2l2 protein, ratNF-E2-Related Factor 2Organophosphorus CompoundsRepressor ProteinsUbiquinoneKelch-like epichlorohydrin-associated protein 1mitoquinonenuclear factor E2-related factor 2prohibitin 2ratssubarachnoid hemorrhage

Identifiers

PMID30890112
PMCPMC6433519
OpenAlexW2924791331

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.