據(jù)美國(guó)物理學(xué)家組織網(wǎng)近日?qǐng)?bào)道，美國(guó)約翰·霍普金斯大學(xué)醫(yī)學(xué)院在細(xì)胞的“能量工廠”線粒體中發(fā)現(xiàn)了一種與血壓控制有關(guān)的蛋白質(zhì),，其數(shù)量會(huì)隨著年齡增長(zhǎng)而下降,。經(jīng)動(dòng)物實(shí)驗(yàn)證明,，抗高血壓藥物氯沙坦（losartan）能增加這種蛋白質(zhì)的數(shù)量，使細(xì)胞恢復(fù)較年輕水平,。該發(fā)現(xiàn)有助于為那些與線粒體相關(guān)的老年病帶來(lái)新的治療方法,，如糖尿病、聽(tīng)力下降,、身體衰弱和帕金森?。ㄕ耦澛楸裕┑取Ｑ芯堪l(fā)表在美國(guó)《國(guó)家科學(xué)院院刊》網(wǎng)站上,。
根據(jù)以往研究顯示,，改變細(xì)胞內(nèi)血管緊張素（angiotensin）水平會(huì)影響線粒體制造能量?；羝战鹚贯t(yī)學(xué)院老年醫(yī)學(xué)教授杰里米·沃爾斯頓和副教授彼得·阿貝德對(duì)血管緊張素在線粒體中的作用進(jìn)行了深入研究,。他們用高倍顯微鏡觀察了小鼠的腎臟、肝臟,、心肌細(xì)胞和人類(lèi)白細(xì)胞,，在線粒體內(nèi)發(fā)現(xiàn)了血管緊張素和它的一種受體，并確定了該受體在線粒體中的位置,。
“我們發(fā)現(xiàn)線粒體中的血管緊張素有一套獨(dú)立運(yùn)作的控制系統(tǒng),，能對(duì)線粒體內(nèi)的能量調(diào)控產(chǎn)生影響。”沃爾斯頓說(shuō),，“該系統(tǒng)可以被一種醫(yī)療中常用的降壓藥來(lái)激活,，當(dāng)收到藥物信號(hào)時(shí),，能同時(shí)影響細(xì)胞的氧化氮水平和能量制造。”
研究小組用化學(xué)方法激活血管緊張素受體來(lái)觀察細(xì)胞的反應(yīng),，發(fā)現(xiàn)細(xì)胞的耗氧量下降了一半,，而產(chǎn)生的氧化氮有所增加。沃爾斯頓解釋說(shuō),，這表明線粒體制造了更少的能量,，降低了血壓。
研究人員對(duì)幼年和老年鼠線粒體中血管緊張素進(jìn)行了檢測(cè),，發(fā)現(xiàn)老年鼠線粒體血管緊張素受體Ⅱ型的數(shù)量降低了近1/3,，這表明老年鼠的細(xì)胞已經(jīng)不能控制能量的使用。他們用降壓藥物氯沙坦對(duì)這些老年鼠進(jìn)行了20周的治療,，發(fā)現(xiàn)它們細(xì)胞中血管緊張素受體的數(shù)量增加了,。“用氯沙坦治療老年鼠，可以使受體數(shù)量顯著增加,，這對(duì)血壓有好處并能降低炎癥,。”沃爾斯頓說(shuō)。
研究人員表示,，他們下一步將從細(xì)胞培養(yǎng)和動(dòng)物實(shí)驗(yàn)轉(zhuǎn)到人類(lèi)實(shí)驗(yàn),，希望開(kāi)發(fā)新的治療方法。在老年人?；嫉母黝?lèi)慢性疾病中,，很多都與線粒體功能衰退有關(guān)，沃爾斯頓說(shuō)：“我們的發(fā)現(xiàn)有助于找到那些能介入受體的藥物,，增進(jìn)線粒體功能，提高能量制造水平,，幫助治療各種老年慢性病,。”(生物谷 Bioon.com)
doi:10.1073/pnas.1101507108
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PMID:
Identification and characterization of a functional mitochondrial angiotensin system
Abadir, Peter M.; Foster, D. Brian; Crow, Michael; Cooke, Carol A.; Rucker, Jasma J.; Jain, Alka; Smith, Barbara J.; Burks, Tyesha N.; Cohn, Ronald D.; Fedarko, Neal S.; Carey, Robert M.; O’Rourke, Brian; Walston, Jeremy D.
The renin-angiotensin (Ang) system regulates multiple physiological functions through Ang II type 1 and type 2 receptors.Prior studies suggest an intracellular pool of Ang II that may be released in an autocrine manner upon stretch to activatesurface membrane Ang receptors. Alternatively, an intracellular renin-Ang system has been proposed, with a primary focus onnuclear Ang receptors. A mitochondrial Ang system has not been previously described. Here we report that functional Ang IItype 2 receptors are present on mitochondrial inner membranes and are colocalized with endogenous Ang. We demonstrate thatactivation of the mitochondrial Ang system is coupled to mitochondrial nitric oxide production and can modulate respiration.In addition, we present evidence of age-related changes in mitochondrial Ang receptor expression, i.e., increased mitochondrialAng II type 1 receptor and decreased type 2 receptor density that is reversed by chronic treatment with the Ang II type 1receptor blocker losartan. The presence of a functional Ang system in human mitochondria provides a foundation for understandingthe interaction between mitochondria and chronic disease states and reveals potential therapeutic targets for optimizing mitochondrialfunction and decreasing chronic disease burden with aging.
