May 30, 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:

New leads to treat tremors

Depleting dopamine in the rat brain striatum, with a neurotoxin that kills dopamine-secreting cells, causes motor impairments like those of Parkinson’s disease. Though the molecular mechanisms responsible are poorly understood, changes in protein phosphorylation – a modification that alters protein activity – have been implicated.

Roger Colbran, Ph.D., and colleagues previously showed that dopamine depletion in rats increases phosphorylation of CaMKII, a protein whose function is critical to normal neuronal physiology. They now report that dopamine depletion significantly decreases the activity of PP1-gamma1, a protein that normally dephosphorylates CaMKII and other synaptic proteins, which could explain why these proteins are hyper-phosphorylated. The reduced PP1-gamma1 activity appears to be caused by its enhanced association with the scaffolding molecule spinophilin. The findings in the May 23 Journal of Biological Chemistry suggest that strategies aimed at increasing the activity of proteins like PP1-gamma1 might normalize phosphorylation levels and effectively treat some symptoms of Parkinson’s disease.

— Leigh MacMillan

Dopamine adapts to drinking

The biological basis of alcohol addiction is puzzling because the pleasant immediate effects of alcohol consumption would seemingly be outweighed in the long term by the discomfort and illness associated with withdrawal. In the laboratory of Danny Winder, Ph.D., Thomas Kash, Ph.D., and Julie Healey studied the brain adaptations that may underlie the continuing desire for alcohol, focusing specifically on the brain’s dopaminergic system, the key neurotransmitter pathway involved in reward.

In mice exposed to alcohol vapors either continuously or intermittently (which mimics repeated binge drinking and withdrawal), they found that markers of dopamine activity varied across the brain regions examined. For example, intermittent exposure increased dopamine transporter (DAT) levels in the nucleus accumbens, a forebrain pleasure and reward center, whereas continuous exposure decreased DAT in that region. The findings, appearing in the May Alcohol, suggest that chronic alcohol exposure and subsequent withdrawal can cause region-specific alterations in dopamine transmission in reward-related brain circuits, a phenomenon that may explain some of the behavioral consequences of chronic alcohol exposure.

— Melissa Marino

Protein marks malignant skin cancer

A recently described class of proteins may offer pathologists additional guidance in distinguishing benign from malignant moles. Minichromosome maintenance, or MCM, proteins are involved in DNA replication and are only seen in dividing cells. Their presence in various cancer types is associated with more advanced disease and poorer prognosis.

Alan Boyd, M.D., and colleagues investigated whether MCM protein expression might offer additional information that could help differentiate benign from malignant skin moles. The researchers compared the expression of MCM2 – one of the most extensively evaluated of the MCM proteins – in benign moles, precancerous moles, primary melanomas and melanoma metastases. They report in the May Journal of the American Academy of Dermatology that MCM2 expression was significantly increased in melanomas compared to benign and precancerous moles. There was no difference, however, between primary melanomas and melanoma metastases. These results suggest that MCM proteins may be a useful marker to aid in the diagnosis of skin cancer.

— Melissa Marino

All breast tumors not created equal

Breast cancer – the leading cancer type for women in the United States – is a heterogeneous disease. But differences in the biology of individual tumors that may have implications for treatment and prognosis are not usually discernible based on microscopic features alone.

To explore the molecular characteristics of breast cancers, Melinda Sanders, M.D., and colleagues examined protein expression in human breast tumors and normal breast tissue using MALDI mass spectrometry. The investigators “captured” cells for analysis with a laser microdissection tool. From the resulting mass spectra, they identified candidate biomarkers and developed algorithms to classify samples as breast tumor or normal breast tissue and to classify tumors by their estrogen receptor status (positive or negative). The results, reported in the April Journal of Proteome Research, support using proteomic analysis to find molecular features of breast tumors that may improve understanding of the disease and guide clinical decisions.

— Leigh MacMillan

Past Aliquots

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