Calcineurin plays a modulatory role in loading-induced regulation of type I myosin heavy chain gene expression in slow skeletal muscle.

Calcineurin plays a modulatory role in loading-induced regulation of type I myosin heavy chain gene expression in slow skeletal muscle.
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钙调神经磷酸酶在慢骨骼肌中负载诱导的 I 型肌球蛋白重链基因表达调节中发挥调节作用。

DOI:
10.1152/ajpregu.00349.2009
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发表时间:
2009
期刊:
American journal of physiology. Regulatory, integrative and comparative physiology
影响因子:
--
通讯作者:
Haddad,Fadia
Haddad,Fadia
中科院分区:
--
文献类型:
--
作者:
Pandorf,ClayE;Jiang,WeihuaH;Qin,AnqiX;Bodell,PaulW;Baldwin,KennethM;Haddad,Fadia

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钙调神经磷酸酶(Cn)在骨骼肌纤维型表达中的作用一直是一个非常感兴趣的课题,因为有报道表明它控制慢肌表型。为了描述Cn在表型重塑中的作用,特别是其在驱动I型肌球蛋白重链(MHC)基因表达中的作用,我们使用了一种新的策略,即在不存在和存在环孢菌素A(CsA)(Cn抑制剂)的情况下诱导和检查从快速到慢速纤维类型的深刻转变。为了诱导从快到慢的转变,我们首先将大鼠进行7天的后肢悬吊(HS)+甲状腺激素[三碘甲腺原氨酸(T3)]以抑制比目鱼肌中I型MHC mRNA的几乎所有表达。然后停止HS + T3给药,大鼠恢复正常的Amphibia和甲状腺状态,在此期间给予溶剂或CsA(30 mg·kg-1·d-1)7或14 d。结果表明,尽管Cn显著抑制,但I型MHC的前mRNA、mRNA和蛋白丰度在再负荷期间相对于HS + T3显著增加(P< 0.05)。I型MHC的表达,但是,衰减CsA与车辆治疗相比。此外,IIa和IIx型MHC前mRNA,mRNA和相对蛋白质水平增加,在Cn治疗的大鼠相比,溶剂治疗。这些发现表明,Cn在MHC转录中具有调节作用,而不是作为慢MHC基因表达的主要调节因子的作用。
The role of calcineurin (Cn) in skeletal muscle fiber-type expression has been a subject of great interest because of reports indicating that it controls the slow muscle phenotype. To delineate the role of Cn in phenotype remodeling, particularly its role in driving expression of the type I myosin heavy chain (MHC) gene, we used a novel strategy whereby a profound transition from fast to slow fiber type is induced and examined in the absence and presence of cyclosporin A (CsA), a Cn inhibitor. To induce the fast-to-slow transition, we first subjected rats to 7 days of hindlimb suspension (HS) + thyroid hormone [triiodothyronine (T3)] to suppress nearly all expression of type I MHC mRNA in the soleus muscle. HS + T3was then withdrawn, and rats resumed normal ambulation and thyroid state, during which vehicle or CsA (30 mg·kg−1·day−1) was administered for 7 or 14 days. The findings demonstrate that, despite significant inhibition of Cn, pre-mRNA, mRNA, and protein abundance of type I MHC increased markedly during reloading relative to HS + T3(P< 0.05). Type I MHC expression was, however, attenuated by CsA compared with vehicle treatment. In addition, type IIa and IIx MHC pre-mRNA, mRNA, and relative protein levels were increased in Cn-treated compared with vehicle-treated rats. These findings indicate that Cn has a modulatory role in MHC transcription, rather than a role as a primary regulator of slow MHC gene expression.
成年比目鱼肌中钙调神经磷酸酶的药理学抑制作用所诱导的表型转变需要甲状腺激素。
DOI: 10.1152/ajpendo.00173.2007
发表时间: 2008
期刊: American journal of physiology. Endocrinology and metabolism
影响因子: --
作者:
N. Koulmann;L. Bahi;F. Ribera;H. Sanchez;B. Serrurier;R. Chapot;A. Peinnequin;R. Ventura;X. Bigard
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通过 RT-PCR 分析肌球蛋白重链 mRNA 表达。
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发表时间: 1997
期刊: Journal of applied physiology (Bethesda, Md. : 1985)
影响因子: --
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DOI: --
发表时间: 2000
期刊: --
影响因子: --
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DOI: 10.1152/ajpcell.2000.279.4.c915
发表时间: 2000-10-01
影响因子: 5.5
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Swoap, SJ;Hunter, RB;Kandarian, SC
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DOI: 10.1101/gad.12.16.2499
发表时间: 1998-08-15
影响因子: 10.5
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