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Autophagy：组蛋白脱乙酰化酶抑制剂可通过FOXO1依赖的途径诱导自噬

2015-05-10 MedSci MedSci原创

自噬肿瘤细胞死亡组蛋白脱乙酰酶抑制剂mTOR
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自噬是细胞在饥饿、低氧及其他应激状态下，为维持细胞内代谢稳态，而进行的一种分解代谢过程。研究发现，组蛋白脱乙酰化酶抑制剂


自噬是细胞在饥饿、低氧及其他应激状态下，为维持细胞内代谢稳态，而进行的一种分解代谢过程。研究发现，组蛋白脱乙酰化酶抑制剂(HDACIs)，可通过抑制雷帕霉素（MTOR）途径诱导细胞自噬。FOXO1，是受蛋白激酶B（AKT）调节的转录因子，在诱导自噬过程中非常重要的作用。

但是，目前关于FOXO1在HDACIs诱导的自噬过程中所起的作用尚无报道。近来，有研究首次分别在mRNA和蛋白水平，证明了HDACIs可以增加FOXO1的表达。同时，还发现HDACIs可以通过增加FOXO1的核聚集和提高FOXO1的转录活性。此外，通过siRNA敲除技术或者特殊的化学抑制剂，可抑制FOXO1的功能，从而显著的抑制HDACIs诱导的细胞自噬。研究者还发现，FOXO1介导的自噬是通过激活FOXO1的转录获得的，最终使诱导细胞自噬表现出双重的效应：1）提高自噬相关基因（ATG）的表达；2）通过SESN3 (sestrin 3)基因的转录抑制MTOR信号途径。最终，研究者发现抑制自噬可以显著提高HDACIs介导的细胞死亡，这提示自噬是有助于细胞存活的重要机制。
    
综上所述，研究者认为，在HDACIs介导的人类肿瘤细胞的自噬中，FOXO1其非常重要的作用，将HDACIs与自噬抑制剂结合应用，有望成为新型的抗肿瘤治疗策略。

参考文献：

Zhang J, Ng S, Wang J, Histone deacetylase inhibitors induce autophagy through FOXO1-dependent pathways.Autophagy. 2015 Apr 3;11(4):629-42. .

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    2016-03-18 jklm09

    #抑制剂#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1851245, encodeId=850f185124564, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Fri Mar 18 09:00:00 CST 2016, time=2016-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=23444, encodeId=57ba2344451, content=看看, beContent=null, objectType=article, channel=null, level=null, likeNumber=144, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ee0d1618732, createdName=huaxipanxing, createdTime=Wed May 13 21:22:00 CST 2015, time=2015-05-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=23252, encodeId=69c02325227, content=求助这篇文章, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=42.203.95.**, createdTime=Tue May 12 23:32:00 CST 2015, time=2015-05-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1384650, encodeId=7d6a138465006, content=<a href='/topic/show?id=5c74e7739f0' target=_blank style='color:#2F92EE;'>#组蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77739, encryptionId=5c74e7739f0, topicName=组蛋白)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ea13490, createdName=xqptu, createdTime=Tue May 12 12:00:00 CST 2015, time=2015-05-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1533931, encodeId=dd8f15339310e, content=<a href='/topic/show?id=132ee62484' target=_blank style='color:#2F92EE;'>#FOXO1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7624, encryptionId=132ee62484, topicName=FOXO1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c82812497085, createdName=许安, createdTime=Tue May 12 12:00:00 CST 2015, time=2015-05-12, status=1, ipAttribution=)]
    2015-05-13 huaxipanxing

    看看

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1851245, encodeId=850f185124564, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Fri Mar 18 09:00:00 CST 2016, time=2016-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=23444, encodeId=57ba2344451, content=看看, beContent=null, objectType=article, channel=null, level=null, likeNumber=144, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ee0d1618732, createdName=huaxipanxing, createdTime=Wed May 13 21:22:00 CST 2015, time=2015-05-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=23252, encodeId=69c02325227, content=求助这篇文章, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=42.203.95.**, createdTime=Tue May 12 23:32:00 CST 2015, time=2015-05-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1384650, encodeId=7d6a138465006, content=<a href='/topic/show?id=5c74e7739f0' target=_blank style='color:#2F92EE;'>#组蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77739, encryptionId=5c74e7739f0, topicName=组蛋白)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ea13490, createdName=xqptu, createdTime=Tue May 12 12:00:00 CST 2015, time=2015-05-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1533931, encodeId=dd8f15339310e, content=<a href='/topic/show?id=132ee62484' target=_blank style='color:#2F92EE;'>#FOXO1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7624, encryptionId=132ee62484, topicName=FOXO1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c82812497085, createdName=许安, createdTime=Tue May 12 12:00:00 CST 2015, time=2015-05-12, status=1, ipAttribution=)]
    2015-05-12 42.203.95.**

    求助这篇文章

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1851245, encodeId=850f185124564, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Fri Mar 18 09:00:00 CST 2016, time=2016-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=23444, encodeId=57ba2344451, content=看看, beContent=null, objectType=article, channel=null, level=null, likeNumber=144, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ee0d1618732, createdName=huaxipanxing, createdTime=Wed May 13 21:22:00 CST 2015, time=2015-05-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=23252, encodeId=69c02325227, content=求助这篇文章, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=42.203.95.**, createdTime=Tue May 12 23:32:00 CST 2015, time=2015-05-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1384650, encodeId=7d6a138465006, content=<a href='/topic/show?id=5c74e7739f0' target=_blank style='color:#2F92EE;'>#组蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77739, encryptionId=5c74e7739f0, topicName=组蛋白)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ea13490, createdName=xqptu, createdTime=Tue May 12 12:00:00 CST 2015, time=2015-05-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1533931, encodeId=dd8f15339310e, content=<a href='/topic/show?id=132ee62484' target=_blank style='color:#2F92EE;'>#FOXO1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7624, encryptionId=132ee62484, topicName=FOXO1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c82812497085, createdName=许安, createdTime=Tue May 12 12:00:00 CST 2015, time=2015-05-12, status=1, ipAttribution=)]
    2015-05-12 xqptu

    #组蛋白#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1851245, encodeId=850f185124564, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Fri Mar 18 09:00:00 CST 2016, time=2016-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=23444, encodeId=57ba2344451, content=看看, beContent=null, objectType=article, channel=null, level=null, likeNumber=144, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ee0d1618732, createdName=huaxipanxing, createdTime=Wed May 13 21:22:00 CST 2015, time=2015-05-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=23252, encodeId=69c02325227, content=求助这篇文章, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=42.203.95.**, createdTime=Tue May 12 23:32:00 CST 2015, time=2015-05-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1384650, encodeId=7d6a138465006, content=<a href='/topic/show?id=5c74e7739f0' target=_blank style='color:#2F92EE;'>#组蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77739, encryptionId=5c74e7739f0, topicName=组蛋白)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ea13490, createdName=xqptu, createdTime=Tue May 12 12:00:00 CST 2015, time=2015-05-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1533931, encodeId=dd8f15339310e, content=<a href='/topic/show?id=132ee62484' target=_blank style='color:#2F92EE;'>#FOXO1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7624, encryptionId=132ee62484, topicName=FOXO1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c82812497085, createdName=许安, createdTime=Tue May 12 12:00:00 CST 2015, time=2015-05-12, status=1, ipAttribution=)]
    2015-05-12 许安

    #FOXO1#

    0

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