May 29, 2009

Aliquots — research highlights from VMC laboratories

Raymond Harris and Ming-Zhi Zhang Raymond Harris, left, and Ming-Zhi Zhang are studying the neurotransmitter dopamine’s role in renal function, blood pressure regulation and life span. (Joe Howell/Vanderbilt)

Fats vs. proteins

Oxidative stress induced by toxic chemicals, inflammation and other environmental factors sparks the formation of lipid “electrophiles.” These reactive fat molecules can attack and damage other cellular components, particularly cellular proteins. Although lipid electrophiles are thought to contribute to a host of diseases, little is known about the scope of protein damage these molecules can cause.

Using new proteomic approaches and chemical affinity capture techniques, Dan Liebler, Ph.D., and colleagues are identifying protein targets of one lipid electrophile, called 4-hydroxy-2-nonenal (HNE). In the April issue of Molecular and Cellular Proteomics, they report identification of more than 400 protein targets that are damaged by HNE. Among the targets were proteins involved in protein folding and degradation, the translation of RNA to protein, and a large network of ribonucleoproteins (which manage processing and transport of RNA). The findings provide an important basis for understanding the mechanisms of oxidant-induced stress and its role in many disease processes.

Melissa Marino


Pregnancy trouble scrambles kidneys

Placental insufficiency – a pregnancy complication in which the placenta cannot deliver enough oxygen and nutrients to the developing baby – is associated with increased infant mortality and diseases later in life. The kidney is particularly sensitive to placental insufficiency late in pregnancy when it is undergoing rapid growth.

Mark de Caestecker, M.D., Ph.D., and colleagues explored how placental insufficiency affects development of the renal medulla – the innermost part of the kidney. They report in the April Journal of the American Society of Nephrology that mice with late gestation placental insufficiency – caused by inactivation of the gene Cited1 in the placenta – have abnormal growth and patterning (dysplasia) of the renal medulla. They show that the dysplasia is associated with decreased tissue oxygen levels and increased apoptosis (cell death) in the expanding renal medulla.

The study provides direct evidence that placental insufficiency promotes renal medullary dysplasia and introduces a novel model for exploring how placental insufficiency causes kidney defects.

Leigh MacMillan


Stomach bug on the map

Helicobacter pylori infection increases gastric cancer risk, but not all infected persons develop cancer. However, one bacterial protein, CagA, increases this risk. Once inside a stomach cell, CagA is modified at sites containing the amino acid sequence EPIYA, which then induces cellular changes similar to those seen in cancer development. The number and type of EPIYA motifs vary by geographic region, suggesting that variations in these motifs might influence regional differences in gastric cancer risk.

Richard Peek, Jr., M.D., and colleagues examined EPIYA variations among H. pylori strains isolated from a high-risk gastric cancer region – Colombia (South America) – and a low-risk region – Nashville. They found that CagA proteins from strains isolated from persons with precancerous lesions contained more motifs, and that precancerous strains from Nashville caused increased production of an inflammatory molecule, IL-8, than Colombian strains. The results reported in the April 15 Journal of Infectious Diseases suggest that geographical differences in gastric cancer risk might be influenced by variations in CagA.

Melissa Marino


Controlling a daughter’s inheritance

Each time a cell divides, it must ensure that both of the resulting cells contain a full complement of specialized cellular structures called organelles. To explore organelle inheritance, Christopher Hardy, Ph.D., and colleagues are studying how the vacuole (an organelle involved in breaking down molecules) is divided between “mother” and “daughter” cells in the budding yeast S. cerevisiae. As a mother cell begins to bud, a “segregation structure” forms to actively transport a portion of the vacuole into the bud. The segregation structure then resolves, splitting the vacuole in two, but mechanisms regulating this event are unknown.

Now, Clinton Bartholomew, Ph.D., and Hardy report a series of findings in the April issue of Eukaryotic Cell that suggest roles for two protein kinases (Cla4 and Ste20) in resolving the segregation structure. Both proteins are localized to and activated in the bud, and their activity is required for degradation of a protein called Vac17, which has been implicated in segregation structure formation and vacuolar inheritance.

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:

Past Aliquots

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