Abstract：
:The cardiac ryanodine receptor-Ca2+ release channel (RyR2) is an essential sarcoplasmic reticulum (SR) transmembrane protein that plays a central role in excitation-contraction coupling (ECC) in cardiomyocytes. Aberrant spontaneous, diastolic Ca2+ leak from the SR due to dysfunctional RyR2 contributes to the formation of delayed after-depolarisations, which are thought to underlie the fatal arrhythmia that occurs in both heart failure (HF) and in catecholaminergic polymorphic ventricular tachycardia (CPVT). CPVT is an inherited disorder associated with mutations in either the RyR2 or a SR luminal protein, calsequestrin. RyR2 shows normal function at rest in CPVT but the RyR2 dysfunction is unmasked by physical exercise or emotional stress, suggesting abnormal RyR2 activation as an underlying mechanism. Several potential mechanisms have been advanced to explain the dysfunctional RyR2 observed in HF and CPVT, including enhanced RyR2 phosphorylation status, altered RyR2 regulation at luminal/cytoplasmic sites and perturbed RyR2 intra/inter-molecular interactions. This review considers RyR2 dysfunction in the context of the structural and functional modulation of the channel, and potential therapeutic strategies to stabilise RyR2 function in cardiac pathology.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Blayney LM,Lai FAdoi
10.1016/j.pharmthera.2009.03.006subject
Has Abstractpub_date
2009-08-01 00:00:00pages
151-77issue
2eissn
0163-7258issn
1879-016Xpii
S0163-7258(09)00053-9journal_volume
123pub_type
杂志文章,评审abstract：:RSV infection of the lower respiratory tract in infants is the leading cause of pediatric hospitalizations and second to malaria in causing infant deaths worldwide. RSV also causes substantial morbidity in immunocompromised and elderly populations. The only available therapeutic is a prophylactic drug called Palivizum...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
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更新日期：2020-10-27 00:00:00
abstract：:The receptor tyrosine kinase MERTK is aberrantly expressed in numerous human malignancies, and is a novel target in cancer therapeutics. Physiologic roles of MERTK include regulation of tissue homeostasis and repair, innate immune control, and platelet aggregation. However, aberrant expression in a wide range of liqui...
journal_title：Pharmacology & therapeutics
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更新日期：2020-09-01 00:00:00
abstract：:Nitric oxide (NO) exerts a variety of biological actions under both physiological and pathological conditions. NO is synthesized by three distinct NO synthase (NOS) isoforms, including neuronal (nNOS), inducible (iNOS), and endothelial NOS (eNOS), all of which are expressed in the human cardiovascular system. The role...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
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更新日期：2010-12-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
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更新日期：2010-07-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(93)90069-p
更新日期：1993-09-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
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更新日期：2008-09-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
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更新日期：1993-01-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
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更新日期：2018-01-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
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更新日期：2013-07-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
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更新日期：1991-12-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2014.12.005
更新日期：2015-04-01 00:00:00
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pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2014.11.015
更新日期：2015-04-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(99)00062-5
更新日期：2000-03-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2016.09.011
更新日期：2016-12-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(90)90035-z
更新日期：1990-01-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2010.09.005
更新日期：2011-02-01 00:00:00
abstract：:Hepatic methionine adenosyltransferase (MAT) deficiency is caused by mutations in the human MAT1A gene that abolish or reduce hepatic MAT activity that catalyzes the synthesis of S-adenosylmethionine from methionine and ATP. This genetic disorder is characterized by isolated persistent hypermethioninemia in the absenc...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(99)00047-9
更新日期：2000-01-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2010.04.004
更新日期：2010-09-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
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更新日期：2016-08-01 00:00:00
abstract：:Necrosis of skeletal muscle is produced by two types of snake venom components: single chain peptides consisting of 42-44 amino acid residues and phospholipases A2 representing either single chain proteins or existing as complexes of several enzyme subunits or combined with other nonenzymatic proteins. Vacuolation, ly...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
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更新日期：1990-01-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章
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更新日期：2000-07-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107555
更新日期：2020-08-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2004.11.009
更新日期：2005-05-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2015.06.009
更新日期：2015-10-01 00:00:00
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journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2009.08.002
更新日期：2010-01-01 00:00:00
abstract：:Cardiovascular diseases (CVDs) remain the leading cause of death in the developed countries. Taking into account the mounting evidence about the role of cytochrome P450 (CYP) enzymes in cardiovascular physiology, CYP polymorphisms can be considered one of the major determinants of individual susceptibility to CVDs. On...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2009.12.002
更新日期：2010-03-01 00:00:00
abstract：:Aside from their pharmacokinetic properties, e.g. their speed of action and the duration of residual effects, benzodiazepines are still considered as equivalent in terms of their effects on cognition. Here we review evidence suggesting that certain benzodiazepines, especially lorazepam, differ in a number of respects,...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2010.01.004
更新日期：2010-04-01 00:00:00
abstract：:Polycyclic aromatic hydrocarbons (PAH) are carcinogens requiring metabolic activation to react with cellular macromolecules, the initial event in carcinogenesis. Cytochrome P450 mediates binding of PAH to DNA by two pathways of activation. One-electron oxidation to form radical cations is the major pathway of activati...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(92)90015-r
更新日期：1992-01-01 00:00:00
abstract：:The nuclear transport proteins, importins and exportins (karyopherin-β proteins), may play an important role in cancer by transporting key mediators of oncogenesis across the nuclear membrane in cancer cells. During nucleocytoplasmic transport of tumor suppressor proteins and cell cycle regulators during the processin...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2016.03.020
更新日期：2016-08-01 00:00:00
abstract：:Glucose-6-phospate dehydrogenase (G6PD) deficiency is estimated to affect more than 400 million people world-wide. This X-linked genetic deficiency puts stress on red blood cells (RBC), which may be further augmented under certain pathophysiological conditions and drug treatments. These conditions can cause hemolytic ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107788
更新日期：2020-12-14 00:00:00
