July 14, 2011

Aliquots — research highlights from VUMC laboratories


Protein loss sets up pro-tumor state

Breakdown of the gut lining is associated with inflammatory bowel disorders and colon cancer. Previously, Albert Reynolds, Ph.D., and colleagues showed that the protein p120 helps maintain integrity of the gut lining in mice and its loss may play a role in inflammatory bowel disorders. However, these mice did not survive long enough to investigate the protein’s role in cancer formation.

Now, using a different mouse model that eliminates p120 expression in about 10 percent of the intestinal epithelium, the investigators have found that 45 percent of mice with focal (limited) p120 loss developed colon tumors within 18 months. However, none of the tumors showed complete loss of p120, suggesting that p120 loss promotes tumor formation indirectly.

The findings published recently in PLoS ONE suggest that p120 loss may set up an environment that allows an increased rate of mutation in tissues subjected to chronic inflammation, and that tumor formation may be driven by a lifelong inability to heal chronic wounds in such an environment.

— Melissa Marino


Dad’s diet influences birth timing

Preterm birth – before 37 weeks of gestation – is the leading cause of infant mortality and morbidity in industrialized nations. Inflammation, frequently associated with infection, is a well-known cause of preterm birth.



Kaylon Bruner-Tran, Ph.D., Kevin Osteen, Ph.D., and their research team are exploring the possibility that environmental pollutants – such as dioxins – promote inappropriate inflammation and disrupt pregnancy. They previously demonstrated that in utero exposure of male mice to a certain dioxin increased the risk of preterm birth following mating to unexposed females. Earlier findings also indicated that toxicant exposure of male mice increased the placental inflammatory response, disrupting communication at the maternal-fetal interface. The researchers now report that providing a diet high in anti-inflammatory omega-3 fatty acids (fish oil) to toxicant-exposed males prior to mating eliminated preterm birth in unexposed females and was associated with a reduction in placental inflammatory response.

This study, published in the journal Reproduction, suggests that the father’s diet before conception can be modulated to prevent toxicant-associated inflammation and preterm birth.

— Leigh MacMillan


Stress circuitry key to drug relapse

Dopamine, the “feel good” brain chemical at the focus of most drug addiction research, helps reinforce drug use. But the negative aspects of drug addiction – e.g., stress-induced relapse – involve other brain systems that may represent therapeutic targets for combating relapse.

Danny Winder, Ph.D., and colleagues are examining the involvement of the adrenergic system and corticotrophin-releasing factor receptor (CRFR) signaling – systems involved in the body’s stress response – in the brain’s response to cocaine. They recorded electrical activity in mouse brain slices and found that activation of beta-adrenergic receptors in the BNST, a region of the amygdala, enhances excitatory neurotransmission through a circuit involving CRFR. Chronic cocaine administration transiently disrupts this enhancement of excitatory neurotransmission. This disruption wanes over time, but can later be recovered by cocaine administration.

The results, in the June 1 issue of Biological Psychiatry, reveal circuitry within the BNST that may play an important role in drug-seeking behaviors and suggest that this circuitry could provide targets for therapies aimed at preventing relapse.

— Melissa Marino


Give me some skin

Our skin stands between us and our environment – it protects us from pathogens and forms a barrier to water loss. Defects in the water barrier can result in dry, thickened, scaly skin – symptoms of a group of mostly genetic skin diseases called ichthyoses.



The essential fatty acid linoleate and two epidermal lipoxygenase enzymes (12R-LOX and eLOX3) are required for formation of the mammalian skin barrier – deficiencies in linoleate or either enzyme cause skin disease. However, the precise roles of these key players are poorly understood. Now, in a Journal of Biological Chemistry “Paper of the Week,” Alan Brash, Ph.D., and colleagues report a novel biochemical pathway by which 12R-LOX and eLOX3 act on linoleate to generate the skin barrier. The researchers demonstrate that the enzymes oxidize linoleate linked to ceramide. This releases the linoleate and frees the ceramide to bind to protein and form the “corneocyte lipid envelope,” a crucial component of the epidermal barrier. Understanding this pathway has implications for the treatment of ichthyoses.

— Leigh MacMillan


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: aliquots@vanderbilt.edu.

Past Aliquots

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