據(jù)美國物理學(xué)家組織網(wǎng)近日報道,，美國約翰·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)量會隨著年齡增長而下降。經(jīng)動物實驗證明，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)的老年病帶來新的治療方法，如糖尿病,、聽力下降,、身體衰弱和帕金森病（振顫麻痹）等,。研究發(fā)表在美國《國家科學(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）水平會影響線粒體制造能量,。霍普金斯醫(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立運作的控制系統(tǒng),，能對線粒體內(nèi)的能量調(diào)控產(chǎn)生影響,。”沃爾斯頓說，“該系統(tǒng)可以被一種醫(yī)療中常用的降壓藥來激活,，當(dāng)收到藥物信號時,，能同時影響細(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,，這表明線粒體制造了更少的能量,，降低了血壓。
研究人員對幼年和老年鼠線粒體中血管緊張素進(jìn)行了檢測,，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,，這對血壓有好處并能降低炎癥,。”沃爾斯頓說。
研究人員表示，他們下一步將從細(xì)胞培養(yǎng)和動物實驗轉(zhuǎn)到人類實驗,，希望開發(fā)新的治療方法,。在老年人常患的各類慢性疾病中,，很多都與線粒體功能衰退有關(guān),，沃爾斯頓說：“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.
