News Release

JCI table of contents: November 22, 2006

Peer-Reviewed Publication

JCI Journals

EDITOR'S PICK: Altered sodium channel function linked to heart failure

The results of a study, using mice and heart muscle cells from rabbits, by researchers from Georg-August-University Göttingen, Germany, have provided a potential molecular explanation for the abnormally rapid heartbeats known as ventricular tachyarrhythmias (VTs) that can cause the sudden death associated with heart failure.

Individuals who inherit mutations in genes regulating the influx of sodium ions (Na+) into the muscle cells of the heart through Na+ channels are predisposed to life-threatening VTs. So, because a protein known as calmodulin regulates Na+ channel function, and expression and activity of the calmodulin effector CaMKII is upregulated in humans with heart failure, Maier and colleagues investigated the effect of CaMKII on Na+ channel function. In this study, which appears online on November 22 in advance of publication in the December print issue of the Journal of Clinical Investigation, it was shown that overexpression of CaMKII in cultured heart muscle cells from rabbits and as a transgene in mice altered Na+ channel function. CaMKII mediated these effects by binding Na+ channel components and phosphorylating them. Importantly, mice overexpressing CaMKII were more susceptible to VTs than normal mice. These data lead the authors to suggest that CaMKII regulation of Na+ channel function might be a contributing factor to the onset of the potentially life-threatening VTs that are associated with heart failure.

TITLE: Ca2+/calmodulin-dependent protein kinase II regulates cardiac Na+ channels

AUTHOR CONTACT:

Lars S. Maier
Georg-August-University Göttingen, Göttingen, Germany.
Phone: +49-551-399481; Fax: +49-551-398941; E-mail: lmaier@med.uni-goettingen.de.

View the PDF of this article at: https://www.the-jci.org/article.php?id=26620


GASTROENTEROLOGY: Spot the difference: proteasome composition differs in Crohn disease and ulcerative colitis

Crohn disease (CD) and ulcerative colitis (UC) are the two most common inflammatory bowel diseases. Both are caused by chronic inflammation in the intestine, although the types of inflammation underlying these disorders differ -- CD is characterized by a Th1 inflammatory response and UC by a Th2 inflammatory response. One potential molecular explanation for the different types of inflammation observed in these two diseases is reported in a study that appears online on November 22 in advance of publication in the December print issue of the Journal of Clinical Investigation. In this study, Ulrich Steinhoff and colleagues at the Max Planck Institute of Infection Biology, Germany, showed that the composition of enzymatic complexes that degrade proteins (known as proteasomes) in the inflamed mucosa of patients with CD differed markedly from the composition of proteasomes in the mucosa of healthy individuals. By contrast, proteasomes in the inflamed mucosa of patients with UC differed only slightly from those in healthy individuals. These differences meant that proteasomes from individuals with CD were more efficient at degrading an inhibitor of NF-kappa-B and processing an NF-kappa-B precursor than proteasomes from individuals with UC, such that the inflammatory mucosa of patients with CD had increased amounts of active NF-kappa-B, an inducer of pro-inflammatory gene expression. This study therefore provides a potential molecular explanation for the different inflammatory responses underlying CD and UC.

TITLE: Proteasome-mediated degradation of I-kappa-B-alpha and processing of p105 in Crohn disease and ulcerative colitis

AUTHOR CONTACT:

Ulrich Steinhoff
Max Planck Institute of Infection Biology, Berlin, Germany.
Phone: +49-30-28460-560; Fax: +49-30-28460-503; E-mail: steinhoff@mpiib-berlin.mpg.de.

View the PDF of this article at: https://www.the-jci.org/article.php?id=28804

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