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Aliquots ó research highlights from VUMC laboratories

6/21/2012 -  

Low oxygen in the kidney

Hypoxia – too little oxygen – is associated with fibrosis (scarring), inflammation and the progression of chronic kidney disease. Hypoxia-inducible factors (HIF) regulate cellular responses to hypoxia, but the role of these factors in kidney disease has not been established.

Volker Haase, M.D., and colleagues used a genetic approach to address the role of HIF in an experimental mouse model of chronic kidney disease. They report in the May 15 Journal of Immunology that activation of HIF ameliorated inflammation and reduced renal fibrosis, whereas deletion of HIF enhanced renal inflammation. Activating or deleting HIF only in macrophage cells demonstrated the importance of HIF signaling in these cells. The researchers also showed that hypoxia and/or activation of the HIF pathway in the kidney reduced the expression of pro-inflammatory chemokines and chemokine receptors.

The findings suggest that hypoxia and HIF activation may be protective in chronic kidney disease and support further studies of HIF as a potential target for controlling inflammation in this setting.

This research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (DK081646, DK081420, DK019525) of the National Institutes of Health.

Leigh MacMillan

 

Receptor’s role in fasting brain circuitry

(iStockphoto.com)

(iStockphoto.com)

Defects in the melanocortin-4 receptor cause a genetic obesity syndrome in humans and have implicated melanocortin brain circuitry in regulating long-term energy balance. The role of the melanocortin-3 receptor (MC3-R) in modulating energy balance is less clear. Deletion of the MC3-R gene in mice causes mild obesity, without hyperphagia (abnormally increased appetite) or hypometabolism.

Roger Cone, Ph.D., and colleagues have now characterized the mechanistic changes underlying this mild obesity syndrome. They report in the June 5 Proceedings of the National Academy of Sciences that mice missing MC3-R have defective responses to fasting, such as blunted mobilization of fatty acids from adipose tissue and reduced activation of the central hypothalamic-pituitary-adrenal signaling axis. These defects alter nutrient distribution and increase fat tissue. The researchers also showed that MC3-R deletion resulted in a Cushing-like syndrome with elevated levels of corticosteroids.

The findings suggest a specific role for MC3-R-containing brain circuits in communicating nutritional status and in regulating nutrient distribution in response to fasting.

This research was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (DK078850) of the National Institutes of Health and by the VA Medical Research Service.

Leigh MacMillan

 

Spelling out HIV risk in urban China

Dramatic economic and social changes in China over the past 30 years have transformed attitudes toward sexuality. As risky sexual activity is increasingly common in both the general population and college students, sexually transmitted infections, once rare in China, have been rapidly increasing and are particularly high in some large Chinese cities.

(iStockphoto.com)

(iStockphoto.com)

Han-Zhu Qian, M.D., Ph.D., MPH and colleagues compared the risks of HIV and syphilis infection among student and non-student men who have sex with other men in a metropolitan city in southwestern China.

They report in PLoS ONE that overall HIV and syphilis rates were high. But although the prevalence of risky sexual behaviors was similar in both groups, HIV rate among students was one-quarter of that in non-students (5.5 percent in students versus 20.9 percent in non-students). There was no significant difference in syphilis rate between two groups. The authors caution that the actual HIV rate among students might be higher due to the shorter time the student population has been sexually active.

The research was supported by grants from the National Institute of Allergy and Infectious Diseases (AI078933, AI094562) and the Fogarty International Center (TW001035) of the National Institutes of Health, the Ministry of Science and Technology of China, and the Chinese State Key Laboratory for Infectious Disease.

Melissa Marino

 

Kids’ cells okay after maternal cancer

Mitochondria – cellular structures known as the “power plants” of the cell – are inherited exclusively from the mother. These organelles contain their own DNA (mtDNA), which is highly vulnerable to damage by environmental insults – for example radiation exposure to the ovaries during treatment for childhood cancer.

Because such damage could be passed on to the offspring of female cancer survivors, John Boice, Jr., Sc.D., and colleagues evaluated mtDNA of 18 mothers who had been treated for cancer as children and their 26 children.

They reported in the May 15 Mutation Research that nine of the 18 families had at least one child who inherited mutated mtDNA. However, there was no significant difference in the number of single nucleotide polymorphisms (mutations in a single “letter” of the DNA code) between mother and child, and radiation dose to the mothers’ ovaries was not linked to mtDNA mutations in offspring.

The results suggest that radiation therapy in female children does not affect mitochondrial mutation rate, and therefore may not increase future cancer risk in the offspring of those survivors.

The research was funded by a grant from the National Cancer Institute (CA104666) of the National Institutes of Health.

Melissa Marino

 

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
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