Effect of chronic obstructive pulmonary disease on calcium pump ATPase expression in human diaphragm.

Effect of chronic obstructive pulmonary disease on calcium pump ATPase expression in human diaphragm.
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慢性阻塞性肺疾病对人膈肌钙泵 ATP 酶表达的影响。

DOI:
10.1152/japplphysiol.00767.2004
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发表时间:
2005
期刊:
Journal of applied physiology (Bethesda, Md. : 1985)
影响因子:
--
通讯作者:
Levine,Sanford
Levine,Sanford
中科院分区:
--
文献类型:
--
作者:
Nguyen,Taitan;Rubinstein,NealA;Vijayasarathy,Camasamudram;Rome,LawrenceC;Kaiser,LarryR;Shrager,JosephB;Levine,Sanford

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我们先前已经证明,由严重的慢性阻塞性肺疾病(COPD)引起的人类横隔膜重塑的特征是肌球蛋白重链亚型由快变慢。为了验证COPD诱导的横隔膜重塑也引起骨骼肌中另一种主要的ATPase--肌内质网Ca~(2+)-ATPase(SERCA)--由快变慢的假说,我们在术中采集了10例重度COPD患者和10例对照组的肋膈组织标本。然后,我们使用针对SERCA异构体的特异性单抗来表征隔膜纤维的SERCA异构体的表达。与对照组相比,慢阻肺隔膜中仅表达快SerCA(即Serca 1;P<0.001)的纤维减少了63%,同时含有快和慢Serca亚型的纤维增加了190%(P<0.01),仅表达慢Serca亚型(即Serca 2)的纤维增加了19%(P<0.05)。此外,在横隔膜匀浆上进行的免疫印迹实验表明,COPD横隔膜的SERCA1含量仅为对照横隔膜的三分之一;相比之下,COPD和对照横隔膜的SERCA2含量没有差异。这些组织学和免疫印迹结果的结合符合这样的假设,即重度COPD引起的横隔膜重塑以快到慢的SERCA异构体转化为特征。此外,结合这些SERCA数据和我们之前报道的肌球蛋白重链亚型数据(Levine S,Nguyen T,Kaiser LR,Rubinstein na,Maislin G,Gregory C,Roman LC,Dudley GA,Sieck GC和Shrager JB.Am J Respir Crit Care Med168:706-713,2003),表明严重COPD引起的横隔膜重塑应该会减少横隔膜对ATP的利用。
We have previously demonstrated that human diaphragm remodeling elicited by severe chronic obstructive pulmonary disease (COPD) is characterized by a fast-to-slow myosin heavy chain isoform transformation. To test the hypothesis that COPD-induced diaphragm remodeling also elicits a fast-to-slow isoform shift in the sarcoendoplasmic reticulum Ca2+ATPase (SERCA), the other major ATPase in skeletal muscle, we obtained intraoperative biopsies of the costal diaphragm from 10 severe COPD patients and 10 control subjects. We then used isoform-specific monoclonal antibodies to characterize diaphragm fibers with respect to the expression of SERCA isoforms. Compared with control diaphragms, COPD diaphragms exhibited a 63% decrease in fibers expressing only fast SERCA (i.e., SERCA1;P< 0.001), a 190% increase in fibers containing both fast and slow SERCA isoforms (P< 0.01), and a 19% increase (P< 0.05) in fibers expressing only the slow SERCA isoform (i.e., SERCA2). Additionally, immunoblot experiments carried out on diaphragm homogenates indicated that COPD diaphragms expressed only one-third the SERCA1 content noted in control diaphragms; in contrast, COPD and control diaphragms did not differ with respect to SERCA2 content. The combination of these histological and immunoblot results is consistent with the hypothesis that diaphragm remodeling elicited by severe COPD is characterized by a fast-to-slow SERCA isoform transformation. Moreover, the combination of these SERCA data and our previously reported myosin heavy chain isoform data (Levine S, Nguyen T, Kaiser LR, Rubinstein NA, Maislin G, Gregory C, Rome LC, Dudley GA, Sieck GC, and Shrager JB.Am J Respir Crit Care Med168: 706–713, 2003) suggests that diaphragm remodeling elicited by severe COPD should decrease ATP utilization by the diaphragm.
DOI: 10.1111/j.1432-1033.1984.tb08154.x
发表时间: 1984
期刊: European journal of biochemistry
影响因子: --
作者:
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通讯作者: Martonosi,A
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发表时间: 2001
影响因子: 5.7
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DOI: --
发表时间: 1988
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影响因子: --
作者:
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DOI: 10.1164/arrd.1983.128.1.54
发表时间: 1983-01-01
期刊: AMERICAN REVIEW OF RESPIRATORY DISEASE
影响因子: --
作者:
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发表时间: 1982
影响因子: 2.7
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