Baidu
map

JCMM:HIF-1α激活瞬时受体TRPC通道促进轻度缺氧心肌细胞肥大

2012-03-08 MedSci MedSci原创

近日,国际著名杂志《细胞与分子医学期刊》(Journal of Cellular and Molecular Medicine)发表了哈尔滨医科大学的一项研究成果,首次证实了轻度缺氧HIF-1α可以调控心肌肥厚,可望为生理性或病理性心肌肥厚的防治提供新的靶点和药物干预策略。 这篇题为《缺氧诱导因子HIF-1α激活瞬时受体TRPC通道促进轻度缺氧心肌细胞肥大》的论文是哈医大药学院青年专家初文峰教授

近日,国际著名杂志《细胞与分子医学期刊》(Journal of Cellular and Molecular Medicine)发表了哈尔滨医科大学的一项研究成果,首次证实了轻度缺氧HIF-1α可以调控心肌肥厚,可望为生理性或病理性心肌肥厚的防治提供新的靶点和药物干预策略。

这篇题为《缺氧诱导因子HIF-1α激活瞬时受体TRPC通道促进轻度缺氧心肌细胞肥大》的论文是哈医大药学院青年专家初文峰教授在杨宝峰院士的指导下完成的研究成果。
 
据课题组成员初文峰教授介绍,体育锻炼人群或高原性心脏病人均可出现心肌肥厚。其中,氧浓度的变化是一种细胞生理学的基本特征,长期的慢性缺氧作为一个重要诱因参与到心肌肥厚的发生发展过程之中。而细胞内钙浓度([Ca2+]i) 的增高为诱发心肌肥厚的重要机制之一,但在缺氧条件下其增高机制尚不明确。缺氧应答中起重要作用的转录因子是缺氧诱导因子HIF-1α,在细胞缺氧时细胞内HIF-1α显著增高。如瞬时受体电位通道(TRP),在细胞凋亡、增殖、分化过程中起重要调节作用,其亚型TRPC1,TRPC3和TRPC6在心肌细胞中存在且与心肌肥厚发生密切相关,电生理学特征为一种钙通透的非选择性阳离子通道。
 
该课题采用电生理学、影像学和分子生物学等实验技术,在证明轻度缺氧(10% O2)造成心肌细胞肥大的基础上,进一步阐明其机制与HIF-1α的表达上调,从而激活TRPC3,TRPC6通道,并导致外钙内流引起 [Ca 2+ ]i的增加,增高的[Ca2+]i继而激活参与心肌细胞肥大关键调节分子-活化T细胞核因子(NFAT)信号通路有关。
 
该研究首次证实了轻度缺氧时HIF-1α调控心肌肥厚,并为生理性或病理性心肌肥厚的防治提供新的靶点和药物干预策略,对人们如何在缺氧条件下进行科学锻炼保护心脏具有指导意义。

NCoR1 Is a Conserved Physiological Modulator of Muscle Mass and Oxidative Function

Hiroyasu Yamamoto, Evan G. Williams, Laurent Mouchiroud, Carles Cantó, Weiwei Fan, Michael Downes, Christophe Héligon, Grant D. Barish, Béatrice Desvergne, Ronald M. Evans et al.

Transcriptional coregulators control the activity of many transcription factors and are thought to have wide-ranging effects on gene expression patterns. We show here that muscle-specific loss of nuclear receptor corepressor 1 (NCoR1) in mice leads to enhanced exercise endurance due to an increase of both muscle mass and of mitochondrial number and activity. The activation of selected transcription factors that control muscle function, such as MEF2, PPARβ/, and ERRs, underpins these phenotypic alterations. NCoR1 levels are decreased in conditions that require fat oxidation, resetting transcriptional programs to boost oxidative metabolism. Knockdown of gei-8, the sole C. elegans NCoR homolog, also robustly increased muscle mitochondria and respiration, suggesting conservation of NCoR1 function. Collectively, our data suggest that NCoR1 plays an adaptive role in muscle physiology and that interference with NCoR1 action could be used to improve muscle function.

版权声明:
本网站所有内容来源注明为“梅斯医学”或“MedSci原创”的文字、图片和音视频资料,版权均属于梅斯医学所有。非经授权,任何媒体、网站或个人不得转载,授权转载时须注明来源为“梅斯医学”。其它来源的文章系转载文章,或“梅斯号”自媒体发布的文章,仅系出于传递更多信息之目的,本站仅负责审核内容合规,其内容不代表本站立场,本站不负责内容的准确性和版权。如果存在侵权、或不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。
在此留言
评论区 (2)
#插入话题
  1. [GetPortalCommentsPageByObjectIdResponse(id=1522139, encodeId=2cf0152213927, content=<a href='/topic/show?id=1b34881e59' target=_blank style='color:#2F92EE;'>#HIF-1α#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8817, encryptionId=1b34881e59, topicName=HIF-1α)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=847f11414102, createdName=changfy, createdTime=Sat Mar 10 14:05:00 CST 2012, time=2012-03-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1556012, encodeId=064715560121e, content=<a href='/topic/show?id=b3e98813c3' target=_blank style='color:#2F92EE;'>#HIF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8813, encryptionId=b3e98813c3, topicName=HIF)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=293014689254, createdName=wrj0126, createdTime=Sat Mar 10 14:05:00 CST 2012, time=2012-03-10, status=1, ipAttribution=)]
    2012-03-10 changfy
  2. [GetPortalCommentsPageByObjectIdResponse(id=1522139, encodeId=2cf0152213927, content=<a href='/topic/show?id=1b34881e59' target=_blank style='color:#2F92EE;'>#HIF-1α#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8817, encryptionId=1b34881e59, topicName=HIF-1α)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=847f11414102, createdName=changfy, createdTime=Sat Mar 10 14:05:00 CST 2012, time=2012-03-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1556012, encodeId=064715560121e, content=<a href='/topic/show?id=b3e98813c3' target=_blank style='color:#2F92EE;'>#HIF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8813, encryptionId=b3e98813c3, topicName=HIF)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=293014689254, createdName=wrj0126, createdTime=Sat Mar 10 14:05:00 CST 2012, time=2012-03-10, status=1, ipAttribution=)]
    2012-03-10 wrj0126
Baidu
map
Baidu
map
Baidu
map