November 6, 2009

Aliquots — research highlights from VUMC laboratories

Genes that change with a fast pulse

Atrial fibrillation (AF) – the most common disorder of heart rhythm in the western world – is a major cause of stroke and death. During AF, rapid stimulation of the atria causes structural and electrical remodeling that increases arrhythmia susceptibility.

Katherine Murray, M.D., and colleagues previously showed that rapid electrical stimulation of cultured atrial cells causes electrical remodeling like that seen in AF and in experimental atrial tachycardia (rapid heart rate) in vivo. They have now explored the gene expression changes in rapidly stimulated atrial cells using microarray analysis and real-time quantitative RT-PCR. They identified 758 genes with altered expression and found similarities between the cultured atrial cells and human AF with respect to large-scale patterns of gene expression changes.

They also uncovered novel pathways and molecules that were regulated in both the in vitro model and in vivo. The report in the October Journal of Molecular and Cellular Cardiology demonstrates that cultured atrial cells are a suitable experimental model for investigating tachycardia-induced remodeling.

Leigh MacMillan


Alcohol animates amygdala

Chronic alcohol consumption can cause behavioral changes including increased anxiety and depression, possibly because of alterations to brain regions that regulate emotional behavior, such as the extended amygdala. No studies have examined the impact of in vivo alcohol exposure on neuronal function in the BNST, a principal region of the extended amygdala.

Danny Winder, Ph.D., and colleagues explored how in vivo alcohol exposure affects neuronal signaling in the mouse BNST, using electrophysiological and biochemical methods. They report in the October issue of Neuropsychopharmacology that chronic intermittent ethanol vapor exposure (causing blood alcohol levels of 0.21 percent) increased

They showed that the increase was due to higher levels of a particular NMDA receptor subunit (NR2B). The results suggest that NMDA receptor-mediated signaling is sensitized in the mouse BNST during chronic alcohol exposure, and that it may be a suitable target for moderating the behavioral effects of acute withdrawal from chronic alcohol consumption.

Leigh MacMillan


DNA fixer-upper

Our DNA is constantly being broken – both by environmental insults and during normal cellular processes. If not repaired, the affected cell may die, and if repaired incorrectly, the cell could turn cancerous.

Nonhomologous end joining (NHEJ) is a major DNA repair mechanism with two distinct but related subpathways: a deletional pathway (D-NHEJ) that generates mistakes in the DNA sequence; and a conservative pathway (C-NHEJ) that joins ends precisely without mistakes. But little is known about how these pathways are regulated. Fen Xia, M.D., Ph.D., and colleagues examined the role of a DNA-repair protein (called Mre11) in these repair pathways in human kidney cells.

They found that silencing Mre11 suppressed overall NHEJ efficiency,

Journal of Biological Chemistry

Melissa Marino


Mercury no match for worm neurons

The heavy metal mercury has well known toxic effects on the brain, kidney and lungs. Humans are typically exposed to mercury by inhalation of mercury vapor released from dental amalgam fillings or consumption of seafood containing an organic form of mercury known as methylmercury. While extensively studied, numerous questions remain about the mechanisms of methylmercury toxicity.

Michael Aschner, Ph.D., and colleagues are using the worm C. elegans to investigate methylmercury toxicity. In the Oct. 15 issue of Toxicology and Applied Pharmacology, they report that methylmercury accumulates in the worms, approaching levels toxic to mammals. At high doses, methylmercury was lethal and caused developmental delays.

However, worms that survived the exposure were surprisingly unaffected, showing no perturbations in lifespan, number of offspring, or swimming rate, and exhibiting no neuronal damage. The results suggest that C. elegans may have unique mechanisms for detoxifying, trafficking or metabolizing methylmercury, particularly in neurons, which may point to targets for combating or preventing mercury toxicity.

— Melissa Marino


We welcome suggestions for research to highlight in Aliquots. The items should be primary research articles (no reviews, editorials or commentaries) published within the last two months in a peer-reviewed journal. Please send the article citation (PDF if available) and any other feedback about the column to:

Past Aliquots

June 22, 2012
June 8, 2012
May 11, 2012
April 27, 2012
April 13, 2012
March 30, 2012
March 16, 2012