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Circulation：HDAC4的糖基化修饰可降低糖尿病患者的心衰风险

2019-08-19 MedSci MedSci原创

HDAC4糖尿病心衰糖基化
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在世界范围内，糖尿病和心力衰竭是常见的共发病，具有较高的社会经济影响和稳步增长的发病率，需要更好地了解糖尿病代谢如何促进心功能障碍。矛盾的是，一些降糖药已经被证明会加重心力衰竭，这就提出了一个问题：血糖是如何调节保护性/有害的心脏信号传导的？研究人员发现组蛋白去乙酰化酶4 (HDAC4)的一个亚结构域可能是糖尿病心脏适应性和非适应性信号的分子检查点，并通过小鼠实验进行验证。研究人员发现HDAC4的

在世界范围内，糖尿病和心力衰竭是常见的共发病，具有较高的社会经济影响和稳步增长的发病率，需要更好地了解糖尿病代谢如何促进心功能障碍。矛盾的是，一些降糖药已经被证明会加重心力衰竭，这就提出了一个问题：血糖是如何调节保护性/有害的心脏信号传导的？

研究人员发现组蛋白去乙酰化酶4 (HDAC4)的一个亚结构域可能是糖尿病心脏适应性和非适应性信号的分子检查点，并通过小鼠实验进行验证。

研究人员发现HDAC4的心脏保护性的N端蛋白水解片段在糖尿病患者和小鼠模型体内增强，在体外高糖和高O-GlcNAc条件下也增强。1/2型糖尿病的HDAC4敲除小鼠模型发展出心力衰竭，而野生型小鼠未出现明显的心力衰竭迹象，表明HDAC4可预防糖尿病心脏病。再表达HDAC4的N端片段可以预防HDAC4依赖性的糖尿病心肌病。

在机制上，翻译后HDAC4在642位丝氨酸上的糖基化修饰是产生HDAC4 N端片段的重要步骤，该过程可被Ca2+/钙调素依赖的蛋白激酶II介导的Ser-632位点磷酸化减弱。预防Ser-642位点的糖基化不仅可完全阻断HDAC4 N末端片段的产生，还可促进Ca2+/钙调素依赖的蛋白激酶II介导的Ser-632位点磷酸化，提示翻译后修饰Ser-632位点的磷酸化（心脏损伤性）和Ser-642位点的糖基化（心脏保护性）存在交联作用。

在本研究中，研究人员发现HDAC4 Ser-642位点的糖基化在糖尿病中具有心脏保护作用，可抵消病理性Ca2+/钙调蛋白依赖性蛋白激酶II信号通路。

原始出处：

Mariya Kronlage ， et al.O-GlcNAcylation of Histone Deacetylase 4 Protects the Diabetic Heart From Failure. Circulation. 2019；140：580–594. https：//doi.org/10.1161/CIRCULATIONAHA.117.031942

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    2019-09-27 lingaifan

    #HDAC#

    0

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    2020-07-05 liuquan

    #糖基化修饰#

    0

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    2019-08-21 lfyang

    #糖基化#

    0

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    2019-08-21 ms3994565386320060

    #心衰风险#

    0

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    2019-08-21 xue8604

    #糖尿病患者#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=2003414, encodeId=e84220034144c, content=<a href='/topic/show?id=86d585931d' target=_blank style='color:#2F92EE;'>#HDAC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8593, encryptionId=86d585931d, topicName=HDAC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e07307, createdName=lingaifan, createdTime=Fri Sep 27 23:15:00 CST 2019, time=2019-09-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2085429, encodeId=4872208542948, content=<a href='/topic/show?id=69cde66454a' target=_blank style='color:#2F92EE;'>#糖基化修饰#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76645, encryptionId=69cde66454a, topicName=糖基化修饰)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=28b7142, createdName=liuquan, createdTime=Sun Jul 05 08:15:00 CST 2020, time=2020-07-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1318310, encodeId=9810131831066, content=<a href='/topic/show?id=b5dde6644b1' target=_blank style='color:#2F92EE;'>#糖基化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76644, encryptionId=b5dde6644b1, topicName=糖基化)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=43cb463, createdName=lfyang, createdTime=Wed Aug 21 10:15:00 CST 2019, time=2019-08-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1389463, encodeId=623d138946347, content=<a href='/topic/show?id=8425519625e' target=_blank style='color:#2F92EE;'>#心衰风险#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=51962, encryptionId=8425519625e, topicName=心衰风险)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/101296147/4E6244DB7C1860858424437821E08291/100, createdBy=a6a52500039, createdName=ms3994565386320060, createdTime=Wed Aug 21 10:15:00 CST 2019, time=2019-08-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1474798, encodeId=dd2a14e47981d, content=<a href='/topic/show?id=935fe6718e3' target=_blank style='color:#2F92EE;'>#糖尿病患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76718, encryptionId=935fe6718e3, topicName=糖尿病患者)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a38f7243741, createdName=xue8604, createdTime=Wed Aug 21 10:15:00 CST 2019, time=2019-08-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1569372, encodeId=e44e15693e234, content=<a href='/topic/show?id=1c562e42646' target=_blank style='color:#2F92EE;'>#修饰#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27426, encryptionId=1c562e42646, topicName=修饰)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=29c615505859, createdName=zhangyxzsh, createdTime=Wed Aug 21 10:15:00 CST 2019, time=2019-08-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1042652, encodeId=d26d104265222, content=谢谢MedSci提供最新的资讯, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=misszhang, createdTime=Mon Aug 19 22:15:00 CST 2019, time=2019-08-19, status=1, ipAttribution=)]
    2019-08-21 zhangyxzsh

    #修饰#

    0

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    2019-08-19 misszhang

    谢谢MedSci提供最新的资讯

    0