February 8, 2008

Aliquots — Research highlights from VUMC laboratories

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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.

Stomach bug’s cancer role

About half of the world's population harbors the bacterium Helicobacter pylori — the strongest known risk factor for gastric cancer — in their stomachs. Yet only a fraction of infected individuals develops gastric cancer. H. pylori strains that possess certain virulence factor genes, including cagA, vacA, and oipA, appear most likely to spark cancer.

In the Jan. 15 issue of Cancer Research, Richard Peek, M.D., and colleagues define the contributions of these bacterial virulence factors in H. pylori-mediated carcinogenesis. The investigators infected gerbils with either a carcinogenic wild-type H. pylori strain, which expresses all of these factors, or strains lacking one of the virulence factors. While all strains induced gastric inflammation, strains lacking cagA and oipA showed reduced incidence of cancer, suggesting that these factors are key mediators of the development of H. pylori-induced gastric cancer. The results illustrate the complex interplay of bacterial virulence factors in gastric carcinogenesis and provide a model for understanding how malignancies arise in the context of inflammation.

— Melissa Marino

MOR relief for aches and pains

Morphine and related opiates are clinically effective painkillers, but their precise neuronal sites and modes of action are still unclear. Multiple populations of spinal cord neurons express the morphine mu-opioid receptor (MOR), and Robert Kline and Ronald Wiley, M.D., Ph.D., sought to determine the role of one population — the dorsal horn neurons — in the pain-relieving actions of morphine. Using a targeted toxin, they selectively destroyed the MOR-expressing dorsal horn neurons in rats and tested behavioral responses to thermal and chemical pain stimuli and the effects of morphine in blunting those responses.

The investigators report in the Jan. 23 Journal of Neuroscience that MOR-expressing dorsal horn neurons are not required for protective reflex responses to transient thermal pain, but that these neurons modulate responses to persistent chemical pain and are required for the full analgesic effects of morphine. The findings suggest that the MOR-expressing dorsal horn neurons are part of the body's innate analgesic system and may be a target for new pain-killing strategies.

— Leigh MacMillan

The protein that binds mom and baby

A successful pregnancy requires a carefully choreographed series of events: embryo attachment to the uterus; formation of the decidua, which nurtures the developing embryo, from uterine cells; and development of the placenta from embryonic components. Although numerous signaling pathways govern each of these processes, S.K. Dey, Ph.D., and colleagues now demonstrate a common link that coordinates embryonic and uterine events.

In the Journal of Biological Chemistry, they show that a protein that regulates gene expression, PPAR-delta, plays a central role at various stages of pregnancy. Maternal PPAR-delta is critical for attachment and decidualization, while embryonic PPAR-delta is vital for normal placenta development. The investigators further detail how PPAR-delta interacts with other signaling pathways in embryo attachment and the specification of placental cell types. The evidence that PPAR-delta is a molecular link that coordinates implantation, decidualization, and placenta development may have important implications for spontaneous pregnancy loss and pre-eclampsia. (See related story this page.)

— Susanne Tranguch

“Knockout” mice eat fat, stay thin

After eating, gut hormones called incretins enhance insulin secretion from pancreatic beta-cells to maintain blood glucose levels. These incretins act through two pancreatic incretin receptors, but may also regulate glucose balance independent of insulin secretion.

Julio Ayala, Ph.D., and colleagues explored insulin action in “double incretin receptor knockout” (DIRKO) mice, which lack both incretin receptors. They found that while DIRKO mice fed either regular or high-fat diets demonstrated impaired beta-cell function, this impairment was overcome by enhanced insulin signaling in liver and muscle. Also, even though DIRKO mice consumed a similar fat content as wild-type mice, they were protected from high-fat diet-induced insulin resistance and obesity. The findings, published in the February issue of Diabetes, emphasize the importance of incretin hormones in regulating glucose homeostasis at sites outside of the pancreas, and may have implications for understanding the mechanisms of diabetes drugs like Byetta (exenatide), which are designed to mimic the “incretin effect.”

— Susanne Tranguch

Past Aliquots

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