Evidence map›Paper›PMID 22142024›Full record

ArticleBritish journal of pharmacology2012

17β-Oestradiol inhibits doxorubicin-induced apoptosis via block of the volume-sensitive Cl(-) current in rabbit articular chondrocytes.

Kousuke Kumagai, Shinji Imai, Futoshi Toyoda, Noriaki Okumura, Eiji Isoya, Hiroshi Matsuura, Yoshitaka Matsusue

Open access · hybridAbstract read
In one paragraph

Article in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.1field-weighted citation impact, top 25% 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

17 citing papers in PubMed, 25 citations in OpenAlex.

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  12. 17β-estradiol activates mTOR in chondrocytes by AKT-dependent and AKT-independent signaling pathways.International journal of clinical and experimental pathology · 2015
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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

7 authors at 1 institution in 1 country.

Kousuke KumagaiDepartment of Orthopaedic Surgery, Shiga University of Medical Science, Otsu, Shiga, Japan.
Shinji Imai
Futoshi Toyoda
Noriaki Okumura
Eiji Isoya
Hiroshi Matsuura
Yoshitaka Matsusue
Shiga University of Medical Science · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND PURPOSE Chondrocyte apoptosis contributes to disruption of cartilage integrity in osteoarthritis. Recent evidence suggested that the volume-sensitive organic osmolyte/anion channel [volume-sensitive (outwardly rectifying) Cl(-) current (I(Cl,vol) )] plays a functional role in the development of cell shrinkage associated with apoptosis (apoptotic volume decrease) in several cell types. In this study, we investigated the cellular effects of 17β-oestradiol on doxorubicin-induced apoptotic responses in rabbit articular chondrocytes. EXPERIMENTAL APPROACH Whole-cell membrane currents and cross-sectional area were measured from chondrocytes using a patch-clamp method and microscopic cell imaging, respectively. Caspase-3/7 activity was assayed as an index of apoptosis. KEY RESULTS Addition of doxorubicin (1 µM) to isosmotic bath solution rapidly activated the Cl(-) current with properties similar to those of I(Cl,vol) in chondrocytes. Doxorubicin also gradually decreased the cross-sectional area of chondrocytes, followed by enhanced caspase-3/7 activity; both of these responses were totally abolished by the I(Cl,vol) blocker DCPIB (20 µM). Pretreatment of chondrocytes with 17β-oestradiol (1 nM) for short (approximately 10 min) and long (24 h) periods almost completely prevented the doxorubicin-induced activation of I(Cl,vol) and subsequent elevation of caspase-3/7 activity. These effects of 17β-oestradiol were significantly attenuated by the oestrogen receptor blocker ICI 182780 (10 µM), as well as the phosphatidyl inositol-3-kinase (PI3K) inhibitors wortmannin (100 nM) and LY294002 (20 µM). Testosterone (10 nM) had no effect on the doxorubicin-induced Cl(-) current. CONCLUSIONS AND IMPLICATIONS 17β-Oestradiol prevents the doxorubicin-induced cell shrinkage mediated through activation of I(Cl,vol) and subsequent induction of apoptosis signals, through a membrane receptor-dependent PI3K pathway in rabbit articular chondrocytes.

Indexed as

AnimalsApoptosisCartilage, ArticularCaspase 3Caspase 7Cells, CulturedChloridesChondrocytesDoxorubicinEstradiolEstrogensMaleNADPH OxidasesPatch-Clamp TechniquesPhosphatidylinositol 3-KinasesRabbitsCaspase 3Caspase 7ChloridesDoxorubicinEstradiolEstrogensNADPH OxidasesPhosphatidylinositol 3-KinasesReactive Oxygen Species

Identifiers

PMID22142024
PMCPMC3417499
OpenAlexW1963165149

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.