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Circulation：BOLA3缺陷调控肺动脉高压的内皮细胞代谢和甘氨酸稳态

2019-05-16 MedSci MedSci原创

BOLA3肺动脉高压内皮细胞代谢甘氨酸
关注

控制氧化还原状态和线粒体代谢的金属复合物铁-硫（Fe-S）簇缺陷与肺动脉高压（PH）相关。BOLA3（BolA家族成员3）调节Fe-S合成，BOLA3突变可导致多种线粒体功能异常综合征，一种与PH相关的致死性疾病。但BOLA3在PH中的作用机制尚不明确。研究人员发现在培养的缺氧肺动脉内皮细胞、1/3级肺动脉高压患者的肺和多种肺动脉高压的啮齿动物模型中，内皮BOLA3的表达水平下调，涉及缺氧诱导因子

控制氧化还原状态和线粒体代谢的金属复合物铁-硫（Fe-S）簇缺陷与肺动脉高压（PH）相关。BOLA3（BolA家族成员3）调节Fe-S合成，BOLA3突变可导致多种线粒体功能异常综合征，一种与PH相关的致死性疾病。但BOLA3在PH中的作用机制尚不明确。

研究人员发现在培养的缺氧肺动脉内皮细胞、1/3级肺动脉高压患者的肺和多种肺动脉高压的啮齿动物模型中，内皮BOLA3的表达水平下调，涉及缺氧诱导因子-2α依赖性的转录抑制（通过组蛋白脱乙酰酶介导的组蛋白脱乙酰化）。体外功能获得性和丧失性实验显示，BOLA3调节Fe-S簇的完整性，从而调节含有脂肪的2-草酸脱氢酶，进而控制糖酵解和线粒体呼吸。

siRNA敲低和自然遗传突变时，细胞BOLA3不足可下调甘氨酸裂解系统蛋白H，从而提高胞内的甘氨酸含量。氧化代谢和甘氨酸水平改变时，BOLA3缺乏会促进内皮细胞的增殖、存活和血管收缩，同时降低血管生成能力。此外，研究人员还发现BOLA3缺陷可促进肺动脉高压的组织学和血流动力学表现。值得注意的是，BOLA3表达的治疗效果可被外源性补充甘氨酸逆转。

BOLA3是连接Fe-S依赖性的氧化呼吸和甘氨酸稳态与内皮细胞代谢重编程的关键环节，对肺动脉高压的病理至关重要。本研究为肺动脉高压伴随高血糖综合征和线粒体疾病之间的临床联系提供了分子解释。

原始出处：

Qiujun Yu， et al.BOLA (BolA Family Member 3) Deficiency Controls Endothelial Metabolism and Glycine Homeostasis in Pulmonary Hypertension. Circulation.7 May 2019. https：//doi.org/10.1161/CIRCULATIONAHA.118.035889. 2019；139：2238–2255

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    2019-10-13 changfy

    #稳态#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1646738, encodeId=353a1646e38d0, content=<a href='/topic/show?id=4478e5315e1' target=_blank style='color:#2F92EE;'>#稳态#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75315, encryptionId=4478e5315e1, topicName=稳态)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3ebc23344390, createdName=changfy, createdTime=Sun Oct 13 03:08:00 CST 2019, time=2019-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1969741, encodeId=b2081969e41e0, content=<a href='/topic/show?id=74646881270' target=_blank style='color:#2F92EE;'>#甘氨酸#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=68812, encryptionId=74646881270, topicName=甘氨酸)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c2b4297, createdName=徐岩, createdTime=Tue Jul 23 14:08:00 CST 2019, time=2019-07-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1780438, encodeId=3e7c1e80438e4, content=<a href='/topic/show?id=2bfa361543' target=_blank style='color:#2F92EE;'>#BOLA3#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3615, encryptionId=2bfa361543, topicName=BOLA3)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=38232500109, createdName=1249898am15暂无昵称, createdTime=Sat Mar 28 05:08:00 CST 2020, time=2020-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1925279, encodeId=87fc19252e948, content=<a href='/topic/show?id=26d633354c9' target=_blank style='color:#2F92EE;'>#动脉高压#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33354, encryptionId=26d633354c9, topicName=动脉高压)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Mon Jun 24 11:08:00 CST 2019, time=2019-06-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1529469, encodeId=c7451529469a2, content=<a href='/topic/show?id=ba3be7774b6' target=_blank style='color:#2F92EE;'>#细胞代谢#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77774, encryptionId=ba3be7774b6, topicName=细胞代谢)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=771d11946860, createdName=yangshch, createdTime=Sat May 18 12:08:00 CST 2019, time=2019-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=366368, encodeId=9dd136636864, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82311653708, createdName=医者仁心5538, createdTime=Fri May 17 20:51:39 CST 2019, time=2019-05-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1050842, encodeId=6b1710508428b, content=肺动脉高压表面是罕见病，事实上临床上并不少见，治疗药物虽然有一些，但是整体仍然不理解，可能未来需要采用综合治疗措施。, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=明天jing, createdTime=Fri May 17 00:08:00 CST 2019, time=2019-05-17, status=1, ipAttribution=)]
    2019-07-23 徐岩

    #甘氨酸#

    0

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    2020-03-28 1249898am15暂无昵称

    #BOLA3#

    0

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    2019-06-24 jklm09

    #动脉高压#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1646738, encodeId=353a1646e38d0, content=<a href='/topic/show?id=4478e5315e1' target=_blank style='color:#2F92EE;'>#稳态#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75315, encryptionId=4478e5315e1, topicName=稳态)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3ebc23344390, createdName=changfy, createdTime=Sun Oct 13 03:08:00 CST 2019, time=2019-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1969741, encodeId=b2081969e41e0, content=<a href='/topic/show?id=74646881270' target=_blank style='color:#2F92EE;'>#甘氨酸#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=68812, encryptionId=74646881270, topicName=甘氨酸)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c2b4297, createdName=徐岩, createdTime=Tue Jul 23 14:08:00 CST 2019, time=2019-07-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1780438, encodeId=3e7c1e80438e4, content=<a href='/topic/show?id=2bfa361543' target=_blank style='color:#2F92EE;'>#BOLA3#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3615, encryptionId=2bfa361543, topicName=BOLA3)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=38232500109, createdName=1249898am15暂无昵称, createdTime=Sat Mar 28 05:08:00 CST 2020, time=2020-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1925279, encodeId=87fc19252e948, content=<a href='/topic/show?id=26d633354c9' target=_blank style='color:#2F92EE;'>#动脉高压#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33354, encryptionId=26d633354c9, topicName=动脉高压)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Mon Jun 24 11:08:00 CST 2019, time=2019-06-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1529469, encodeId=c7451529469a2, content=<a href='/topic/show?id=ba3be7774b6' target=_blank style='color:#2F92EE;'>#细胞代谢#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77774, encryptionId=ba3be7774b6, topicName=细胞代谢)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=771d11946860, createdName=yangshch, createdTime=Sat May 18 12:08:00 CST 2019, time=2019-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=366368, encodeId=9dd136636864, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82311653708, createdName=医者仁心5538, createdTime=Fri May 17 20:51:39 CST 2019, time=2019-05-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1050842, encodeId=6b1710508428b, content=肺动脉高压表面是罕见病，事实上临床上并不少见，治疗药物虽然有一些，但是整体仍然不理解，可能未来需要采用综合治疗措施。, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=明天jing, createdTime=Fri May 17 00:08:00 CST 2019, time=2019-05-17, status=1, ipAttribution=)]
    2019-05-18 yangshch

    #细胞代谢#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1646738, encodeId=353a1646e38d0, content=<a href='/topic/show?id=4478e5315e1' target=_blank style='color:#2F92EE;'>#稳态#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75315, encryptionId=4478e5315e1, topicName=稳态)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3ebc23344390, createdName=changfy, createdTime=Sun Oct 13 03:08:00 CST 2019, time=2019-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1969741, encodeId=b2081969e41e0, content=<a href='/topic/show?id=74646881270' target=_blank style='color:#2F92EE;'>#甘氨酸#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=68812, encryptionId=74646881270, topicName=甘氨酸)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c2b4297, createdName=徐岩, createdTime=Tue Jul 23 14:08:00 CST 2019, time=2019-07-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1780438, encodeId=3e7c1e80438e4, content=<a href='/topic/show?id=2bfa361543' target=_blank style='color:#2F92EE;'>#BOLA3#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3615, encryptionId=2bfa361543, topicName=BOLA3)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=38232500109, createdName=1249898am15暂无昵称, createdTime=Sat Mar 28 05:08:00 CST 2020, time=2020-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1925279, encodeId=87fc19252e948, content=<a href='/topic/show?id=26d633354c9' target=_blank style='color:#2F92EE;'>#动脉高压#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33354, encryptionId=26d633354c9, topicName=动脉高压)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Mon Jun 24 11:08:00 CST 2019, time=2019-06-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1529469, encodeId=c7451529469a2, content=<a href='/topic/show?id=ba3be7774b6' target=_blank style='color:#2F92EE;'>#细胞代谢#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77774, encryptionId=ba3be7774b6, topicName=细胞代谢)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=771d11946860, createdName=yangshch, createdTime=Sat May 18 12:08:00 CST 2019, time=2019-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=366368, encodeId=9dd136636864, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82311653708, createdName=医者仁心5538, createdTime=Fri May 17 20:51:39 CST 2019, time=2019-05-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1050842, encodeId=6b1710508428b, content=肺动脉高压表面是罕见病，事实上临床上并不少见，治疗药物虽然有一些，但是整体仍然不理解，可能未来需要采用综合治疗措施。, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=明天jing, createdTime=Fri May 17 00:08:00 CST 2019, time=2019-05-17, status=1, ipAttribution=)]
    2019-05-17 医者仁心5538

    学习了

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1646738, encodeId=353a1646e38d0, content=<a href='/topic/show?id=4478e5315e1' target=_blank style='color:#2F92EE;'>#稳态#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75315, encryptionId=4478e5315e1, topicName=稳态)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3ebc23344390, createdName=changfy, createdTime=Sun Oct 13 03:08:00 CST 2019, time=2019-10-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1969741, encodeId=b2081969e41e0, content=<a href='/topic/show?id=74646881270' target=_blank style='color:#2F92EE;'>#甘氨酸#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=68812, encryptionId=74646881270, topicName=甘氨酸)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c2b4297, createdName=徐岩, createdTime=Tue Jul 23 14:08:00 CST 2019, time=2019-07-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1780438, encodeId=3e7c1e80438e4, content=<a href='/topic/show?id=2bfa361543' target=_blank style='color:#2F92EE;'>#BOLA3#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3615, encryptionId=2bfa361543, topicName=BOLA3)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=38232500109, createdName=1249898am15暂无昵称, createdTime=Sat Mar 28 05:08:00 CST 2020, time=2020-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1925279, encodeId=87fc19252e948, content=<a href='/topic/show?id=26d633354c9' target=_blank style='color:#2F92EE;'>#动脉高压#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33354, encryptionId=26d633354c9, topicName=动脉高压)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Mon Jun 24 11:08:00 CST 2019, time=2019-06-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1529469, encodeId=c7451529469a2, content=<a href='/topic/show?id=ba3be7774b6' target=_blank style='color:#2F92EE;'>#细胞代谢#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77774, encryptionId=ba3be7774b6, topicName=细胞代谢)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=771d11946860, createdName=yangshch, createdTime=Sat May 18 12:08:00 CST 2019, time=2019-05-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=366368, encodeId=9dd136636864, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82311653708, createdName=医者仁心5538, createdTime=Fri May 17 20:51:39 CST 2019, time=2019-05-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1050842, encodeId=6b1710508428b, content=肺动脉高压表面是罕见病，事实上临床上并不少见，治疗药物虽然有一些，但是整体仍然不理解，可能未来需要采用综合治疗措施。, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=明天jing, createdTime=Fri May 17 00:08:00 CST 2019, time=2019-05-17, status=1, ipAttribution=)]
    2019-05-17 明天jing

    肺动脉高压表面是罕见病，事实上临床上并不少见，治疗药物虽然有一些，但是整体仍然不理解，可能未来需要采用综合治疗措施。

    0