ArticleEuropean journal of pharmacology2008
Doxazosin induces apoptosis of cells expressing hERG K+ channels.
Article in European journal of pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- Hsa_circ_0011385 accelerates the progression of thyroid cancer by targeting miR-361-3p.Cancer cell international · 2020Article
- Doxazosin Stimulates Galectin-3 Expression and Collagen Synthesis in HL-1 Cardiomyocytes Independent of Protein Kinase C Pathway.Frontiers in pharmacology · 2016Article
- HERG K+ channel-dependent apoptosis and cell cycle arrest in human glioblastoma cells.PloS one · 2014Article
- Mechanisms of zolpidem-induced long QT syndrome: acute inhibition of recombinant hERG K(+) channels and action potential prolongation in human cardiomyocytes derived from induced pluripotent stem cells.British journal of pharmacology · 2013Article
- Regulation of apoptosis in HL-1 cardiomyocytes by phosphorylation of the receptor tyrosine kinase EphA2 and protection by lithocholic acid.British journal of pharmacology · 2012Article
- Predicting the potency of hERG K⁺ channel inhibition by combining 3D-QSAR pharmacophore and 2D-QSAR models.Journal of molecular modeling · 2012Article
- Novel roles for hERG K(+) channels in cell proliferation and apoptosis.Cell death & disease · 2011Review
- hERG K+ channel-associated cardiac effects of the antidepressant drug desipramine.Naunyn-Schmiedeberg's archives of pharmacology · 2011Article
- Rescue of mutated cardiac ion channels in inherited arrhythmia syndromes.Journal of cardiovascular pharmacology · 2010Review
- Multiple mechanisms of hERG liability: K+ current inhibition, disruption of protein trafficking, and apoptosis induced by amoxapine.Naunyn-Schmiedeberg's archives of pharmacology · 2010Article
- Apoptosis induction by doxazosin and other quinazoline alpha1-adrenoceptor antagonists: a new mechanism for cancer treatment?Naunyn-Schmiedeberg's archives of pharmacology · 2009Article
- Transforming growth factor-beta type I receptor/ALK5 contributes to doxazosin-induced apoptosis in H9C2 cells.Naunyn-Schmiedeberg's archives of pharmacology · 2009Article
- Homozygous missense N629D hERG (KCNH2) potassium channel mutation causes developmental defects in the right ventricle and its outflow tract and embryonic lethality.Circulation research · 2008Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
The antihypertensive drug doxazosin has been associated with an increased risk for congestive heart failure and cardiomyocyte apoptosis. Human ether-a-go-go-related gene (hERG) K(+) channels, previously shown to be blocked by doxazosin at therapeutically relevant concentrations, represent plasma membrane receptors for the antihypertensive drug. To elucidate the molecular basis for doxazosin-associated pro-apoptotic effects, cell death was studied in human embryonic kidney cells using three independent apoptosis assays. Doxazosin specifically induced apoptosis in hERG-expressing HEK cells, while untransfected control groups were insensitive to treatment with the antihypertensive agent. An unexpected biological mechanism has emerged: binding of doxazosin to its novel membrane receptor, hERG, triggers apoptosis, possibly representing a broader pathophysiological mechanism in drug-induced heart failure.
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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.