近日,，首都醫(yī)科大學(xué)教授王松靈課題組與美國(guó)國(guó)立衛(wèi)生研究院,、北京市腫瘤研究所課題組合作,，首次發(fā)現(xiàn)哺乳類(lèi)動(dòng)物細(xì)胞膜的硝酸鹽轉(zhuǎn)運(yùn)通道,。相關(guān)論文發(fā)表在美國(guó)《國(guó)家科學(xué)院院刊》（PNAS）上,。
硝酸鹽是自然界廣泛存在的一種無(wú)機(jī)物,，上世紀(jì)80年代，學(xué)者們發(fā)現(xiàn)機(jī)體可以?xún)?nèi)源性產(chǎn)生硝酸鹽,。盡管硝酸鹽與腫瘤的關(guān)系一直是學(xué)者關(guān)注的重要領(lǐng)域,，但近年來(lái)的研究發(fā)現(xiàn)，人體可還原硝酸鹽，轉(zhuǎn)化為亞硝酸鹽及一氧化氮,，從而發(fā)揮重要的生理功能,。而機(jī)體是如何轉(zhuǎn)運(yùn)硝酸鹽并發(fā)揮功能的機(jī)理尚不清楚。
體內(nèi)循環(huán)的硝酸鹽經(jīng)硝酸鹽還原為亞硝酸鹽,，進(jìn)而產(chǎn)生的一氧化氮在維持全身硝酸根離子和一氧化氮平衡中起著重要作用,，機(jī)體內(nèi)25%的硝酸鹽是由唾液腺攝取分泌至唾液而進(jìn)入胃腸血液再循環(huán)。王松靈課題組的研究表明,，腮腺是機(jī)體調(diào)節(jié)代謝硝酸鹽的重要器官,。課題組利用唾液腺模式器官，通過(guò)國(guó)內(nèi)外合作研究,，以體外細(xì)胞學(xué),、動(dòng)物實(shí)驗(yàn)及唾液酸轉(zhuǎn)運(yùn)蛋白（Sialin）突變所致疾病患者和對(duì)照組研究為基礎(chǔ)，發(fā)現(xiàn)了Sialin是唾液腺細(xì)胞膜硝酸鹽的轉(zhuǎn)運(yùn)通道,。進(jìn)一步研究證實(shí),，經(jīng)Sialin轉(zhuǎn)運(yùn)的硝酸鹽在細(xì)胞內(nèi)可轉(zhuǎn)化為一氧化氮，Sialin在包括腦,、肝,、腎、脾在內(nèi)的機(jī)體重要臟器廣泛高表達(dá),，可能具有潛在的生理意義和臨床應(yīng)用前景,。
細(xì)胞內(nèi)經(jīng)一氧化氮合成酶產(chǎn)生一氧化氮的功能具有重要臨床意義，細(xì)胞在乏氧及酸性條件下經(jīng)合成酶產(chǎn)生的一氧化氮明顯減少,，會(huì)啟動(dòng)補(bǔ)償性系統(tǒng),，產(chǎn)生一氧化氮來(lái)維持細(xì)胞的功能。該研究是首次發(fā)現(xiàn)哺乳類(lèi)動(dòng)物細(xì)胞膜的硝酸鹽轉(zhuǎn)運(yùn)通道,，在機(jī)體硝酸鹽循環(huán)代謝及在維持亞硝酸鹽及一氧化氮穩(wěn)態(tài)方面有重要作用,。（生物谷Bioon.com）
doi:10.1073/pnas.1116633109
PMC:
PMID:
Sialin (SLC17A5) functions as a nitrate transporter in the plasma membrane
Lizheng Qina,1, Xibao Liub,1, Qifei Suna, Zhipeng Fana, Dengsheng Xiaa, Gang Dinga, Hwei Ling Ongb, David Adamsc, William A. Gahlc, Changyu Zhengb, Senrong Qia, Luyuan Jina, Chunmei Zhanga, Liankun Gud, Junqi Hee, Dajun Dengd,2, Indu S. Ambudkarb,2, and Songlin Wanga,e,2
In vivo recycling of nitrate (NO3?) and nitrite (NO2?) is an important alternative pathway for the generation of nitric oxide (NO) and maintenance of systemic nitrate–nitrite–NO balance. 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. Here we report that sialin (SLC17A5), mutations in which cause Salla disease and infantile sialic acid storage disorder (ISSD), functions as an electrogenic 2NO3?/H+ cotransporter in the plasma membrane of salivary gland acinar cells. We have identified an extracellular pH-dependent anion current that is carried by NO3? or sialic acid (SA), but not by Br?, and is accompanied by intracellular acidification. Both responses were reduced by knockdown of sialin expression and increased by the plasma membrane-targeted sialin mutant (L22A-L23A). Fibroblasts from patients with ISSD displayed reduced SA- and NO3?-induced currents compared with healthy controls. Furthermore, expression of disease-associated sialin mutants in fibroblasts and salivary gland cells suppressed the H+-dependent NO3? conductance. Importantly, adenovirus-dependent expression of the sialinH183R mutant in vivo in pig salivary glands decreased NO3? secretion in saliva after intake of a NO3?-rich diet. Taken together, these data demonstrate that sialin mediates nitrate influx into salivary gland and other cell types. We suggest that the 2NO3?/H+ transport function of sialin in salivary glands can contribute significantly to clearance of serum nitrate, as well as nitrate recycling and physiological nitrite-NO homeostasis.
