在新出版的Nature Genetics雜志上，新加坡和德國的科學(xué)家發(fā)現(xiàn),， PYCR1基因發(fā)生突變將導(dǎo)致皮膚過早衰老，也稱之為”皺皮綜合癥(wrinkly skin syndrome)”,。這項發(fā)現(xiàn)不僅說明了PYCR1蛋白質(zhì)水平升高可以緩解快速衰老,、皮膚皺縮癥狀，而且還發(fā)現(xiàn)了某些基因與保持肌膚年輕態(tài)有關(guān),。
研究人員Bruno Reversade及其課題組利用生物信息學(xué)工具,，分析了患“皺皮綜合癥”患者的DNA樣品的信息。研究人員發(fā)現(xiàn)患者的17號染色體PYCR1基因發(fā)生缺陷,，并且發(fā)現(xiàn)該基因發(fā)生某些特異性突變會導(dǎo)致老年人皮膚松弛,，估量丟失，快關(guān)節(jié)脫位以及白內(nèi)障,。
他們還研究了皺皮綜合癥患者的皮膚和骨骼,，這兩種組織受該疾病的影響最嚴重。在正常條件下,，皮膚和骨骼中含有較高水平的PYCR1蛋白,，因此，正對提高PYCR1蛋白活性水平的療法或許能夠減緩衰老的過程,。
PYCR1蛋白位于線粒體內(nèi),。在試驗中，研究人員觀察到PYCR1突變體中線粒體形態(tài)的變化以及結(jié)締組織中細胞死亡,。為了確定PYCR1蛋白減少對機體產(chǎn)生的影響,，研究人員利用基因工程手段關(guān)閉模式生物青蛙和魚的PYCR1基因,，再研究它們的生長狀況。他們發(fā)現(xiàn),，這些動物皮膚的線粒體功能發(fā)生改變,，細胞死亡量增加。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Genetics 41, 1016 - 1021 (2009) 2 August 2009 | doi:10.1038/ng.413
Mutations in PYCR1 cause cutis laxa with progeroid features
Bruno Reversade1,33, Nathalie Escande-Beillard1,33, Aikaterini Dimopoulou2, Bj?rn Fischer2, Serene C Chng1, Yun Li3, Mohammad Shboul1, Puay-Yoke Tham1, Hülya Kayserili4, Lihadh Al-Gazali5, Monzer Shahwan6, Francesco Brancati7,8, Hane Lee9, Brian D O'Connor9, Mareen Schmidt-von Kegler2,10, Barry Merriman9, Stanley F Nelson9, Amira Masri11, Fawaz Alkazaleh11, Deanna Guerra12, Paola Ferrari13, Arti Nanda14, Anna Rajab15, David Markie16, Mary Gray16, John Nelson17, Arthur Grix18, Annemarie Sommer19, Ravi Savarirayan20, Andreas R Janecke21, Elisabeth Steichen22, David Sillence23, Ingrid Hauer24, Birgit Budde25, Gudrun Nürnberg25, Peter Nürnberg25, Petra Seemann10,26, Désirée Kunkel26, Giovanna Zambruno27, Bruno Dallapiccola7, Markus Schuelke28, Stephen Robertson29, Hanan Hamamy6, Bernd Wollnik3,30,31, Lionel Van Maldergem32, Stefan Mundlos2,10,26 & Uwe Kornak2,10
Autosomal recessive cutis laxa (ARCL) describes a group of syndromal disorders that are often associated with a progeroid appearance, lax and wrinkled skin, osteopenia and mental retardation1, 2, 3. Homozygosity mapping in several kindreds with ARCL identified a candidate region on chromosome 17q25. By high-throughput sequencing of the entire candidate region, we detected disease-causing mutations in the gene PYCR1. We found that the gene product, an enzyme involved in proline metabolism, localizes to mitochondria. Altered mitochondrial morphology, membrane potential and increased apoptosis rate upon oxidative stress were evident in fibroblasts from affected individuals. Knockdown of the orthologous genes in Xenopus and zebrafish led to epidermal hypoplasia and blistering that was accompanied by a massive increase of apoptosis. Our findings link mutations in PYCR1 to altered mitochondrial function and progeroid changes in connective tissues.
