Evidence map›Paper›PMID 25863936›Full record

ArticleJournal of neural transmission (Vienna, Austria : 1996)2015

Rasagiline and selegiline suppress calcium efflux from mitochondria by PK11195-induced opening of mitochondrial permeability transition pore: a novel anti-apoptotic function for neuroprotection.

Yuqiu Wu, Kimiko Kazumura, Wakako Maruyama, Toshihiko Osawa, Makoto Naoi

Abstract read
PubMed Publisher
In one paragraph

Article in Journal of neural transmission (Vienna, Austria : 1996), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
3.8field-weighted citation impact, top 6% 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

27 citing papers in PubMed, 48 citations in OpenAlex.

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  16. 90 years of monoamine oxidase: some progress and some confusion.Journal of neural transmission (Vienna, Austria : 1996) · 2018
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 1 country.

Yuqiu WuDepartment of Health and Nutrition, Faculty of Psychological and Physical Science, Aichi Gakuin University, 12 Araike, Iwasaki-cho, Nisshin, Aichi, 470-0195, Japan.
Kimiko KazumuraCentral Research Laboratory, Hamamatsu Photonics, Hamamatsu, Shizuoka, Japan.
Wakako MaruyamaDepartment of Cognitive Brain Science, National Research Center for Geriatrics and Gerontology, Obu, Aichi, Japan.
Toshihiko OsawaDepartment of Health and Nutrition, Faculty of Psychological and Physical Science, Aichi Gakuin University, 12 Araike, Iwasaki-cho, Nisshin, Aichi, 470-0195, Japan.
Makoto NaoiDepartment of Health and Nutrition, Faculty of Psychological and Physical Science, Aichi Gakuin University, 12 Araike, Iwasaki-cho, Nisshin, Aichi, 470-0195, Japan. mnaoi@dpc.agu.ac.jp.
Aichi Gakuin University · JPHamamatsu Photonics (Japan) · JPNational Center for Geriatrics and Gerontology · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Rasagiline and selegiline, inhibitors of type B monoamine oxidase (MAO-B), protect neurons from cell death in cellular and animal models. Suppression of mitochondrial membrane permeabilization and subsequent activation of apoptosis cascade, and induction of anti-apoptotic, pro-survival genes are proposed to contribute the anti-apoptotic function. Rasagiline suppresses neurotoxin- and oxidative stress-induced membrane permeabilization in isolated mitochondria, but the mechanism has been not fully clarified. In this paper, regulation of the mitochondrial permeability transition pore by rasagiline and selegiline was examined in apoptosis induced by PK11195, a ligand of the outer membrane translocator protein 18 kDa (TSPO) in SH-SY5Y cells. The pore opening was quantitatively measured using a simultaneous monitoring system for calcium (Ca(2+)) and superoxide (O2(-)) (Ishibashi et al. in Biochem Biophys Res Commun 344:571-580, 2006). The association of the pore opening with Ca(2+) efflux and ROS increase was proved by the inhibition of Bcl-2 overexpression and cyclosporine A treatment. Potency to release Ca(2+) was correlated with the cytotoxicity of TSPO antagonists, PK11195, FGIN-1-27 and protoporphyrin IX, whereas a TSPO agonist, 4-chloro-diazepamine, did not significantly increase Ca(2+) or cause cell death. Rasagiline and selegiline inhibited mitochondrial Ca(2+) efflux through the mitochondrial permeability transition pore dose dependently. Ca(2+) efflux was confirmed as the initial signal in mitochondrial apoptotic cascade, and the suppression of Ca(2+) efflux may account for the neuroprotective function of rasagiline and selegiline. The quantitative measurement of Ca(2+) efflux can be applied to determine anti-apoptotic activity of neuroprotective compounds. The role of mitochondrial Ca(2+) release in neuronal death and also in neuroprotection by MAO-B inhibitors is discussed.

Indexed as

ApoptosisCalciumCell Line, TumorCyclosporineCytoplasmHumansIndansIndoleacetic AcidsIsoquinolinesMitochondriaMitochondrial Membrane Transport ProteinsMitochondrial Permeability Transition PoreMonoamine Oxidase InhibitorsNeuroprotective AgentsProto-Oncogene Proteins c-bcl-2ProtoporphyrinsBCL2 protein, humanCalciumCyclosporineIndansIndoleacetic AcidsIsoquinolinesMitochondrial Membrane Transport ProteinsMitochondrial Permeability Transition PoreMonoamine Oxidase InhibitorsNeuroprotective AgentsN,N-di-n-hexyl-2-(4-fluorophenyl)indole-3-acetamidePK 11195Proto-Oncogene Proteins c-bcl-2protoporphyrin IXProtoporphyrinsrasagilineReceptors, GABASelegilineSuperoxidesTSPO protein, humanApoptosisCalciumMembrane permeability transition poreMitochondriaNeuroprotectionOuter membrane translocator protein 18 kDaPK11195RasagilineSelegiline

Identifiers

PMID25863936
OpenAlexW2001020719

What OpenQuestion holds

Textmetadata
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.