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Archive - Dec 22, 2011

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Naked Mole-Rat Insensitive to Acid-Induced Pain Due to Altered Ion Channel

British researchers of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch have found out why the African naked mole-rat (Heterocephalus glaber), one of the world's most unusual mammals, feels no pain when exposed to acid. African naked mole-rats live densely packed in narrow dark burrows where ambient carbon dioxide (CO2) levels are very high. In body tissues, CO2 is converted into acid, which continuously activates pain sensors. However, naked mole-rats are an exception: they have an altered ion channel in their pain receptors that is inactivated by acid and makes the animals insensitive to this type of pain. Dr. Ewan St. John Smith and Professor Gary Lewin conclude that this pain insensitivity is due to the African mole-rats' adaptation to their extreme habitat over the course of evolution. The results are published in the December 16, 2011 issue of Science. The Nav1.7 sodium ion channel plays a key role in the transmission of painful stimuli to the brain. It triggers a nerve impulse (action potential) in the pain receptors – sensory nerve cells, the endings of which are found in the skin and which transmit pain signals to the brain. Dentists already use sodium ion channel blockers in the form of local anesthetics, but these target all sodium ion channels they come into contact with, not just the Nav1.7 ion channel. People with defective Nav1.7 ion channels due to a genetic mutation feel no pain, but for them, pain insensitivity is not at all an advantage; minor injuries or infections can go unnoticed, often with serious consequences. However, this is different for the African naked mole-rat. For these animals, pain insensitivity to acid is evidently a survival advantage.

Severe Congenital Disorder Treated Successfully in Mouse Model

Using a mouse model, Heidelberg University Hospital researchers have for the first time successfully treated a severe congenital disorder in which sugar metabolism is disturbed. The team headed by Professor Christian Körner, group leader at the Center for Child and Adolescent Medicine, demonstrated that if female mice are given mannose with their drinking water prior to mating and during pregnancy, their offspring will develop normally even if they carry the genetic mutation for the congenital disorder. The team’s outstanding work will contribute to better understanding of the molecular processes of this metabolic disease, along with the key stages in embryonic development, and may offer a therapeutic approach for the first time. The Heidelberg-based researchers also collaborated with colleagues working with Professor Hermann-Josef Gröne of the German Cancer Research Center (DKFZ)’s Division of Cellular and Molecular Pathology in Heidelberg. Their results were published online on December 11, 2011 in Nature Medicine in advance of their publication in the print edition of that journal. So far, 1,000 children worldwide are affected by congenital disorders of glycosylation (CDG), which are classified as rare diseases. Affecting around 800 children, type CDG-Ia is most frequent. The number of unreported cases is high, however. Children with CDG are severely physically and mentally disabled, with approximately 20 percent dying before the age of two. To date, no therapy has been available to treat the disorder. CDG-Ia is caused by mutations in the genetic information for the enzyme phosphomannomutase 2 which is involved in important glycosylation processes: mannose-1-phosphate is not produced in sufficient quantities.

Fish Oil Metabolite Kills Leukemia Stem Cells in Mice

A compound produced from fish oil that appears to target leukemia stem cells could lead to a cure for the disease, according to Penn State researchers. The compound -- delta-12-protaglandin J3, or D12-PGJ3 -- targeted and killed the stem cells of chronic myelogenous leukemia (CML) in mice, said Dr. Sandeep Prabhu, associate professor of immunology and molecular toxicology in the Department of Veterinary and Medical Sciences. The compound is produced from EPA -- eicosapentaenoic Acid -- an omega-3 fatty acid found in fish and in fish oil, he said. "Research in the past on fatty acids has shown the health benefits of fatty acids on cardiovascular system and brain development, particularly in infants, but we have shown that some metabolites of omega-3 have the ability to selectively kill the leukemia-causing stem cells in mice," said Dr. Prabhu. "The important thing is that the mice were completely cured of leukemia with no relapse." The researchers, who released their findings in the December 22, 2011 issue of Blood, said the compound kills cancer-causing stem cells in the mice's spleen and bone marrow. Specifically, it activates a gene -- p53 -- in the leukemia stem cell that programs the cell's own death. "p53 is a tumor suppressor gene that regulates the response to DNA damage and maintains genomic stability," Dr. Prabhu said. Killing the stem cells in leukemia, a cancer of the white blood cells, is important because stem cells can divide and produce more cancer cells, as well as create more stem cells, Dr. Prabhu said. The current therapy for CML extends the patient's life by keeping the number of leukemia cells low, but the drugs fail to completely cure the disease because they do not target leukemia stem cells, said Dr.