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China-US Cooperative Research Discovers Sialin Function as a Nitrate Transporter in Plasma Membrane

Nitrate is an inorganic compound that widely exists in the nature. In the 1980s, it was discovered that nitrates can be produced endogenously in human body. Though the relationship between nitrates and tumor has long been an important concern, recent researches discover that nitrite (NO2−) and nitric oxide (NO) can be generated from nitrates by human body and undertake important physiological functions, but how the body transports nitrates remains unclear. On July 9, 2012, the PNAS published an article reporting an important progress in this area made by the research group led by Prof. Wang Songling from the Capital Medical University in collaboration with NIH and Beijing Institute for Cancer Research.

The nitrate (NO3−) in vivo recycling and the nitrite (NO2−) and nitric oxide (NO) generated from nitrate play an important role for nitrate–nitrite–NO balance of the body. More than 25% of the circulating NO3− is actively removed and secreted by salivary glands. Oral commensal bacteria convert salivary NO3− to NO2−, which enters circulation and leads to NO generation. The transporters for NO3− in salivary glands have not yet been identified. The previous researches of Prof. Wang’s group found that parotid gland is an important organ in the regulation and metabolism of nitrates. It takes the research group another 10 years to unveil, on the basis of in vitro cytology, animal experiment and studies on mutations which cause Salla disease and infantile sialic acid storage disorder (ISSD), that Sialin (SLC17A5) functions as an electrogenic 2NO3−/H+ cotransporter in the plasma membrane of salivary gland acinar cell. Further research proves that nitrates carried by Sialin can be transferred into nitric oxide and Sialin has high expression in important organs such as brain, liver, kidney and spleen, which could have potential physiological implication and clinical application. The function and clinical significance of nitric oxide generated  by nitric oxide synthase in cells have been well-known, but in acidic or hypoxia conditions, the amount of nitric oxide generated by nitric oxide synthase decreases remarkably and the NO3−-NO2−-NO system starts to generate nitric oxide to maintain cell function. The research is the first that discovers the nitrate transportation mechanism in mammal plasma membrane, which can contribute significantly to clearance of serum nitrate, as well as nitrate recycling and physiological nitrite-NO homeostasis. The research was funded by NSFC key project (No. 30430690).

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