Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q8IXL6 (RNS)
 1,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dysregulation of the myocardial extracellular matrix contributes to abnormal cardiac muscle function. Changes in the balance between matrix deposition and matrix degradation by matrix metalloproteinases (MMPs) can lead to cardiac fibrosis and dilation. In this review, we discuss the regulation of MMPs, their endogenous inhibitors (TIMPs) and collagen synthesis by inflammatory cytokines and reactive oxygen/nitrogen species (ROS/RNS). Inflammatory cytokines, such as interleukin-1beta and tumor necrosis factor-alpha, and ROS activate mitogen-activated protein kinases and stress-responsive protein kinases in cardiac cells. In non-cardiac tissues, inflammatory cytokine activation of these kinases is redox sensitive, suggesting ROS may also be involved in cytokine signaling in the heart. Subsequent activation of transcription factors including AP-1, Ets, and nuclear factor kappa-B leads to increased transcription of MMPs. ROS also directly activate MMPs post-translationally. In addition, inflammatory cytokines and ROS lead to decreased TIMP levels and collagen synthesis. Work in animal models suggests that inhibition of inflammatory cytokine or ROS signaling leads to less myocardial remodeling. Further study of the signaling of regulation of the cardiac extracellular matrix may lead to new approaches for the treatment of myocardial remodeling and failure.
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PMID:Regulation of matrix metalloproteinases by cytokines and reactive oxygen/nitrogen species in the myocardium. 1473 67

In cardiac muscle, a number of posttranslational protein modifications can alter the function of the Ca(2+) release channel of the sarcoplasmic reticulum (SR), also known as the ryanodine receptor (RyR). During every heartbeat RyRs are activated by the Ca(2+)-induced Ca(2+) release mechanism and contribute a large fraction of the Ca(2+) required for contraction. Some of the posttranslational modifications of the RyR are known to affect its gating and Ca(2+) sensitivity. Presently, research in a number of laboratories is focused on RyR phosphorylation, both by PKA and CaMKII, or on RyR modifications caused by reactive oxygen and nitrogen species (ROS/RNS). Both classes of posttranslational modifications are thought to play important roles in the physiological regulation of channel activity, but are also known to provoke abnormal alterations during various diseases. Only recently it was realized that several types of posttranslational modifications are tightly connected and form synergistic (or antagonistic) feed-back loops resulting in additive and potentially detrimental downstream effects. This review summarizes recent findings on such posttranslational modifications, attempts to bridge molecular with cellular findings, and opens a perspective for future work trying to understand the ramifications of crosstalk in these multiple signaling pathways. Clarifying these complex interactions will be important in the development of novel therapeutic approaches, since this may form the foundation for the implementation of multi-pronged treatment regimes in the future. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Cardiac Pathways of Differentiation, Metabolism and Contraction.
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PMID:Posttranslational modifications of cardiac ryanodine receptors: Ca(2+) signaling and EC-coupling. 2296 Jun 42