ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2013
Pharmacological inhibition of calpain-1 prevents red cell dehydration and reduces Gardos channel activity in a mouse model of sickle cell disease.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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.
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.
Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Article
- BDA-410 inhibits SARS-CoV-2 main protease activity and viral replication in mammalian cells.Journal of cellular and molecular medicine · 2022Article
- Rapid degradation of protein tyrosine phosphatase 1B in sickle cells: Possible contribution to sickle cell membrane weakening.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Early and Late-Phase 24 h Responses of Stored Red Blood Cells to Recipient-Mimicking Conditions.Frontiers in physiology · 2022Article
- Article
- Signaling Response to Transient Redox Stress in Human Isolated T Cells: Molecular Sensor Role of Syk Kinase and Functional Involvement of IL2 Receptor and L-Selectine.Sensors (Basel, Switzerland) · 2020Article
- Current challenges in the management of patients with sickle cell disease - A report of the Italian experience.Orphanet journal of rare diseases · 2019Review
- Factor H interferes with the adhesion of sickle red cells to vascular endothelium: a novel disease-modulating molecule.Haematologica · 2019Article
- New Therapeutic Options for the Treatment of Sickle Cell Disease.Mediterranean journal of hematology and infectious diseases · 2019Review
- Calpain-1 regulates platelet function in a humanized mouse model of sickle cell disease.Thrombosis research · 2017Article
- BDA-410 Treatment Reduces Body Weight and Fat Content by Enhancing Lipolysis in Sedentary Senescent Mice.The journals of gerontology. Series A, Biological sciences and medical sciences · 2017Article
- Calpain research for drug discovery: challenges and potential.Nature reviews. Drug discovery · 2016Review
- Genetic inactivation of calpain-1 attenuates pain sensitivity in a humanized mouse model of sickle cell disease.Haematologica · 2016Article
- Identification of signalling cascades involved in red blood cell shrinkage and vesiculation.Bioscience reports · 2015Article
- Calpain 1 inhibitor BDA-410 ameliorates α-klotho-deficiency phenotypes resembling human aging-related syndromes.Scientific reports · 2014Article
- The role of peroxiredoxin II in chemoresistance of breast cancer cells.Breast cancer (Dove Medical Press) · 2014Review
- Calcium in red blood cells-a perilous balance.International journal of molecular sciences · 2013Review
- Oxidative stress and β-thalassemic erythroid cells behind the molecular defect.Oxidative medicine and cellular longevity · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Sickle cell disease (SCD) is a globally distributed hereditary red blood cell (RBC) disorder. One of the hallmarks of SCD is the presence of circulating dense RBCs, which are important in SCD-related clinical manifestations. In human dense sickle cells, we found reduced calpastatin activity and protein expression compared to either healthy RBCs or unfractionated sickle cells, suggesting an imbalance between activator and inhibitor of calpain-1 in favor of activator in dense sickle cells. Calpain-1 is a nonlysosomal cysteine proteinase that modulates multiple cell functions through the selective cleavage of proteins. To investigate the relevance of this observation in vivo, we evaluated the effects of the orally active inhibitor of calpain-1, BDA-410 (30 mg/kg/d), on RBCs from SAD mice, a mouse model for SCD. In SAD mice, BDA-410 improved RBC morphology, reduced RBC density (D(20); from 1106 ± 0.001 to 1100 ± 0.001 g/ml; P<0.05) and increased RBC-K(+) content (from 364 ± 10 to 429 ± 12.3 mmol/kg Hb; P<0.05), markedly reduced the activity of the Ca(2+)-activated K(+)channel (Gardos channel), and decreased membrane association of peroxiredoxin-2. The inhibitory effect of calphostin C, a specific inhibitor of protein kinase C (PKC), on the Gardos channel was eliminated after BDA-410 treatment, which suggests that calpain-1 inhibition affects the PKC-dependent fraction of the Gardos channel. BDA-410 prevented hypoxia-induced RBC dehydration and K(+) loss in SAD mice. These data suggest a potential role of BDA-410 as a novel therapeutic agent for treatment of SCD.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.