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Circulation：MicroRNA-195通过调节去乙酰化酶3的表达和线粒体蛋白乙酰化水平调节衰竭心肌细胞的能量代谢

2018-05-13 MedSci MedSci原创

microRNA-195心力衰竭乙酰化SIRT3
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心力衰竭导致衰竭心肌线粒体功能障碍和代谢异常，并伴有心室重塑。线粒体去乙酰化酶3（SIRT3）通过调节线粒体乙酰基在维持线粒体功能中发挥重要作用。目前已发现某些microRNAs可通过调节心肌的关键信号因子在心室重塑过程中发挥重要作用。现有研究人员对microRNA-195（miR-195）和SIRT3调控心室重塑的机制，及其之间是否存在相互关系进行研究。研究人员通过人类心肌样AC16细胞分析细胞

心力衰竭导致衰竭心肌线粒体功能障碍和代谢异常，并伴有心室重塑。线粒体去乙酰化酶3（SIRT3）通过调节线粒体乙酰基在维持线粒体功能中发挥重要作用。目前已发现某些microRNAs可通过调节心肌的关键信号因子在心室重塑过程中发挥重要作用。现有研究人员对microRNA-195（miR-195）和SIRT3调控心室重塑的机制，及其之间是否存在相互关系进行研究。

研究人员通过人类心肌样AC16细胞分析细胞信号，并检测纯合敲除SIRT3（SIRT3-/-）和过表达microRNA-195（miR-195）的小鼠的乙酰化水平是否发生变化。

研究人员发现，在衰竭的心肌细胞中，诱导miR-195表达会伴随线粒体去乙酰化酶SIRT3的表达量减少、整体蛋白乙酰化水平增强。研究人员对miR-195在SIRT3介导的代谢过程中的作用及其对脱乙酰化的调节酶的影响进行深入研究。全乙酰化蛋白质组学分析显示总体乙酰化水平增强，2个中心线粒体的代谢酶PDH和ATP合成酶的特异性赖氨酸乙酰化作用也增强。miR-195通过直接靶向3’UTR区下调SIRT3的表达。用去乙酰化酶抑制剂尼克酰胺处理、小干扰RNA介导敲除SIRT3或过表达miR-195均可增强PDH复合物和ATP合成酶的乙酰化，削弱PDH和ATP合成酶活性，进而抑制线粒体呼吸。SIRT3-/-和miR-195转基因小鼠的整体蛋白（PDH复合物和ATP合成酶）的乙酰化水平持续增强，而酶活性相应降低。

综上所述，本研究结果表明衰竭心肌细胞的miR-195水平增高，直接抑制SIRT3的表达，并通过增强对心脏能量代谢至关重要的PDH和ATP合成酶的乙酰化水平抑制其活性。

原始出处：

https：//doi.org/10.1161/CIRCULATIONAHA.117.030486

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    2018-08-02 jiafufeng@yaho

    #CRO#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1857647, encodeId=e1cb185e647e6, content=<a href='/topic/show?id=3f48525849' target=_blank style='color:#2F92EE;'>#CRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5258, encryptionId=3f48525849, topicName=CRO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c30265, createdName=jiafufeng@yaho, createdTime=Thu Aug 02 21:05:00 CST 2018, time=2018-08-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2084399, encodeId=d5de20843991d, content=<a href='/topic/show?id=61f411e013b' target=_blank style='color:#2F92EE;'>#Micro#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11701, encryptionId=61f411e013b, topicName=Micro)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, createdName=xjy02, createdTime=Mon Dec 31 04:05:00 CST 2018, time=2018-12-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2060513, encodeId=a18f2060513ac, content=<a href='/topic/show?id=d4183e22569' target=_blank style='color:#2F92EE;'>#去乙酰化酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37225, encryptionId=d4183e22569, topicName=去乙酰化酶)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e2dd327, createdName=许安, createdTime=Mon Jul 02 08:05:00 CST 2018, time=2018-07-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1435720, encodeId=3ba41435e2038, content=<a href='/topic/show?id=31df11e1642' target=_blank style='color:#2F92EE;'>#microRNA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11716, encryptionId=31df11e1642, topicName=microRNA)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Tue May 15 08:05:00 CST 2018, time=2018-05-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1492710, encodeId=ffeb1492e100c, content=<a href='/topic/show?id=7050842e999' target=_blank style='color:#2F92EE;'>#能量代谢#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84279, encryptionId=7050842e999, topicName=能量代谢)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=38b18951187, createdName=amyloid, createdTime=Tue May 15 08:05:00 CST 2018, time=2018-05-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=314931, encodeId=2cce31493182, content=学习学习谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Mon May 14 06:55:37 CST 2018, time=2018-05-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=314777, encodeId=f3ed314e77f5, content=好好, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b5a62240667, createdName=张新亮1853311252142e2fm, createdTime=Sun May 13 18:06:47 CST 2018, time=2018-05-13, status=1, ipAttribution=)]
    2018-12-31 xjy02

    #Micro#

    0

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    2018-07-02 许安

    #去乙酰化酶#

    0

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    2018-05-15 zhouqu_8

    #microRNA#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1857647, encodeId=e1cb185e647e6, content=<a href='/topic/show?id=3f48525849' target=_blank style='color:#2F92EE;'>#CRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5258, encryptionId=3f48525849, topicName=CRO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c30265, createdName=jiafufeng@yaho, createdTime=Thu Aug 02 21:05:00 CST 2018, time=2018-08-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2084399, encodeId=d5de20843991d, content=<a href='/topic/show?id=61f411e013b' target=_blank style='color:#2F92EE;'>#Micro#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11701, encryptionId=61f411e013b, topicName=Micro)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, createdName=xjy02, createdTime=Mon Dec 31 04:05:00 CST 2018, time=2018-12-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2060513, encodeId=a18f2060513ac, content=<a href='/topic/show?id=d4183e22569' target=_blank style='color:#2F92EE;'>#去乙酰化酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37225, encryptionId=d4183e22569, topicName=去乙酰化酶)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e2dd327, createdName=许安, createdTime=Mon Jul 02 08:05:00 CST 2018, time=2018-07-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1435720, encodeId=3ba41435e2038, content=<a href='/topic/show?id=31df11e1642' target=_blank style='color:#2F92EE;'>#microRNA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11716, encryptionId=31df11e1642, topicName=microRNA)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Tue May 15 08:05:00 CST 2018, time=2018-05-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1492710, encodeId=ffeb1492e100c, content=<a href='/topic/show?id=7050842e999' target=_blank style='color:#2F92EE;'>#能量代谢#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84279, encryptionId=7050842e999, topicName=能量代谢)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=38b18951187, createdName=amyloid, createdTime=Tue May 15 08:05:00 CST 2018, time=2018-05-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=314931, encodeId=2cce31493182, content=学习学习谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Mon May 14 06:55:37 CST 2018, time=2018-05-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=314777, encodeId=f3ed314e77f5, content=好好, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b5a62240667, createdName=张新亮1853311252142e2fm, createdTime=Sun May 13 18:06:47 CST 2018, time=2018-05-13, status=1, ipAttribution=)]
    2018-05-15 amyloid

    #能量代谢#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1857647, encodeId=e1cb185e647e6, content=<a href='/topic/show?id=3f48525849' target=_blank style='color:#2F92EE;'>#CRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5258, encryptionId=3f48525849, topicName=CRO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c30265, createdName=jiafufeng@yaho, createdTime=Thu Aug 02 21:05:00 CST 2018, time=2018-08-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2084399, encodeId=d5de20843991d, content=<a href='/topic/show?id=61f411e013b' target=_blank style='color:#2F92EE;'>#Micro#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11701, encryptionId=61f411e013b, topicName=Micro)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, createdName=xjy02, createdTime=Mon Dec 31 04:05:00 CST 2018, time=2018-12-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2060513, encodeId=a18f2060513ac, content=<a href='/topic/show?id=d4183e22569' target=_blank style='color:#2F92EE;'>#去乙酰化酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37225, encryptionId=d4183e22569, topicName=去乙酰化酶)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e2dd327, createdName=许安, createdTime=Mon Jul 02 08:05:00 CST 2018, time=2018-07-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1435720, encodeId=3ba41435e2038, content=<a href='/topic/show?id=31df11e1642' target=_blank style='color:#2F92EE;'>#microRNA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11716, encryptionId=31df11e1642, topicName=microRNA)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Tue May 15 08:05:00 CST 2018, time=2018-05-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1492710, encodeId=ffeb1492e100c, content=<a href='/topic/show?id=7050842e999' target=_blank style='color:#2F92EE;'>#能量代谢#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84279, encryptionId=7050842e999, topicName=能量代谢)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=38b18951187, createdName=amyloid, createdTime=Tue May 15 08:05:00 CST 2018, time=2018-05-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=314931, encodeId=2cce31493182, content=学习学习谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Mon May 14 06:55:37 CST 2018, time=2018-05-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=314777, encodeId=f3ed314e77f5, content=好好, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b5a62240667, createdName=张新亮1853311252142e2fm, createdTime=Sun May 13 18:06:47 CST 2018, time=2018-05-13, status=1, ipAttribution=)]
    2018-05-14 kafei

    学习学习谢谢

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1857647, encodeId=e1cb185e647e6, content=<a href='/topic/show?id=3f48525849' target=_blank style='color:#2F92EE;'>#CRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5258, encryptionId=3f48525849, topicName=CRO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c30265, createdName=jiafufeng@yaho, createdTime=Thu Aug 02 21:05:00 CST 2018, time=2018-08-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2084399, encodeId=d5de20843991d, content=<a href='/topic/show?id=61f411e013b' target=_blank style='color:#2F92EE;'>#Micro#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11701, encryptionId=61f411e013b, topicName=Micro)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, createdName=xjy02, createdTime=Mon Dec 31 04:05:00 CST 2018, time=2018-12-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2060513, encodeId=a18f2060513ac, content=<a href='/topic/show?id=d4183e22569' target=_blank style='color:#2F92EE;'>#去乙酰化酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37225, encryptionId=d4183e22569, topicName=去乙酰化酶)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e2dd327, createdName=许安, createdTime=Mon Jul 02 08:05:00 CST 2018, time=2018-07-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1435720, encodeId=3ba41435e2038, content=<a href='/topic/show?id=31df11e1642' target=_blank style='color:#2F92EE;'>#microRNA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11716, encryptionId=31df11e1642, topicName=microRNA)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Tue May 15 08:05:00 CST 2018, time=2018-05-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1492710, encodeId=ffeb1492e100c, content=<a href='/topic/show?id=7050842e999' target=_blank style='color:#2F92EE;'>#能量代谢#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=75, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84279, encryptionId=7050842e999, topicName=能量代谢)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=38b18951187, createdName=amyloid, createdTime=Tue May 15 08:05:00 CST 2018, time=2018-05-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=314931, encodeId=2cce31493182, content=学习学习谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Mon May 14 06:55:37 CST 2018, time=2018-05-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=314777, encodeId=f3ed314e77f5, content=好好, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b5a62240667, createdName=张新亮1853311252142e2fm, createdTime=Sun May 13 18:06:47 CST 2018, time=2018-05-13, status=1, ipAttribution=)]
    2018-05-13 张新亮1853311252142e2fm

    好好

    0

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