June 12, 2009

Aliquots — research highlights from VUMC laboratories

Heart protein keeps the beat

The rhythmic heartbeat relies on the coordinated release of calcium inside heart muscle cells, a process that is governed by multi-protein complexes called calcium release units (CRUs).

Björn Knollmann, M.D., Ph.D., and colleagues have explored the role of a CRU protein called triadin by evaluating heart muscle cell structure and function in mice lacking the triadin gene. They report in the May 5 Proceedings of the National Academy of Sciences that mouse hearts without triadin have lower levels of other CRU proteins and fewer connections between the cell membrane and the sarcoplasmic reticulum (SR, the internal calcium storage site). The triadin-deficient heart cells also have impaired CRU function, including reduced SR calcium release and faulty feedback systems that lead to cellular calcium overload and ventricular arrhythmias.

The findings demonstrate that triadin has a role in maintaining the structural and functional integrity of the cardiac CRU and suggest that the triadin gene should be considered as a candidate for arrhythmia susceptibility in humans.

Leigh MacMillan


Life and death in the stomach lining

Infection with the gut bacterium Helicobacter pylori increases the risk of gastric cancer, in part by disrupting the delicate balance between cell proliferation and death in the stomach lining.

Brent Polk, M.D., and colleagues examined how H. pylori-induced activation of the epidermal growth factor receptor (EGFR) – a molecule that regulates cell survival – upsets this balance. Using mouse and human gastric cell cultures, as well as mouse models of H. pylori infection, the researchers found that the bacterially induced activation of EGFR protects gastric epithelial cells from programmed cell death (apoptosis) and that blocking this activation increased H. pylori-induced apoptosis. They also identified downstream activation of the Akt and Bcl families of signaling molecules as mediators of this anti-apoptotic response.

The findings reported in the April issue of Gastroenterology offer insights into how H. pylori infection might contribute to the development of gastric cancer and lend support to the concept of targeting EGFR for cancer prevention or treatment.

Melissa Marino


Soy may lower breast cancer risk

Soy foods are rich in estrogen-like compounds (isoflavones) shown to have anti-cancer effects. High soy intake has been linked to a reduced risk of breast cancer. However, some animal studies have implicated isoflavones in stimulating tumor growth, calling the beneficial effects of soy into question.

In the large, prospective, population-based “Shanghai Women’s Health Study,” Wei Zheng, M.D., Ph.D., and colleagues assessed soy intake in 73,223 women. Over the seven and a half year study, 592 women were diagnosed with breast cancer. The researchers found that women who reported consuming a high level of soy foods during adolescence or adulthood had a reduced risk of developing breast cancer before menopause. Soy intake had no affect on breast cancer risk after menopause.

The results – in the June issue of the American Journal of Clinical Nutrition – suggest that soy food intake may reduce the risk of breast cancer in premenopausal women – and may help explain the lower incidence of breast cancer in Asian countries where soy food consumption is high.

Melissa Marino


Tool for tracking mitochondrial DNA

Mitochondria – the “power plants” of cells – have their own genome. Analysis of mitochondrial DNA (mtDNA) has been valuable for studies of human evolution, and variations in mtDNA are being increasingly linked to a variety of diseases.

But existing databases of mtDNA sequences are becoming outdated, and researchers need tools to access and use the constantly updated information in centralized databases like GenBank, the NIH-maintained collection of all publicly available DNA sequences. David Samuels, Ph.D., and colleagues developed mtDNA-GeneSyn, a downloadable software tool that identifies and classifies the variation present in large genetic data sets. They used mtDNA-GeneSyn to analyze the diversity of the 5,140 human mitochondrial genomes in GenBank as of August 2008.

Their report in the May 15 American Journal of Human Genetics provides researchers with a current list of mtDNA variation and the computational tools for carrying out this type of analysis on any mtDNA sequence data sets.

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