Up-regulation of alpha-smooth muscle actin in cardiomyocytes from non-hypertrophic and non-failing transgenic mouse hearts expressing N-terminal truncated cardiac troponin I
| Autor: | J.-P. Jin, Hongguang Wei, Han Zhong Feng, Stephanie Kern, Steven E. Cala |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Genetically modified mouse
α-SKA alpha-skeletal muscle actin Pathology medicine.medical_specialty N-terminal truncation Cardiomyocyte macromolecular substances TnT Troponin T Article cTnI cardiac troponin I General Biochemistry Genetics and Molecular Biology Contractility 03 medical and health sciences 0302 clinical medicine Transgenic mouse Troponin I Medicine cTnI-ND N-terminal truncated cardiac troponin I lcsh:QH301-705.5 Actin 030304 developmental biology 0303 health sciences Smooth muscle tissue Troponin T business.industry α-SMA alpha-smooth muscle actin α-CA alpha-cardiac actin α-SMA Cell biology medicine.anatomical_structure lcsh:Biology (General) Cardiac muscle remodeling TnI troponin I business Myofibril 030217 neurology & neurosurgery Blood vessel |
| Zdroj: | FEBS Open Bio FEBS Open Bio, Vol 4, Iss C, Pp 11-17 (2014) |
| ISSN: | 2211-5463 |
| DOI: | 10.1016/j.fob.2013.11.002 |
| Popis: | We previously reported that a restrictive N-terminal truncation of cardiac troponin I (cTnI-ND) is up-regulated in the heart in adaptation to hemodynamic stresses. Over-expression of cTnI-ND in the hearts of transgenic mice revealed functional benefits such as increased relaxation and myocardial compliance. In the present study, we investigated the subsequent effect on myocardial remodeling. The alpha-smooth muscle actin (α-SMA) isoform is normally expressed in differentiating cardiomyocytes and is a marker for myocardial hypertrophy in adult hearts. Our results show that in cTnI-ND transgenic mice of between 2 and 3 months of age (young adults), a significant level of α-SMA is expressed in the heart as compared with wild-type animals. Although blood vessel density was increased in the cTnI-ND heart, the mass of smooth muscle tissue did not correlate with the increased level of α-SMA. Instead, immunocytochemical staining and Western blotting of protein extracts from isolated cardiomyocytes identified cardiomyocytes as the source of increased α-SMA in cTnI-ND hearts. We further found that while a portion of the up-regulated α-SMA protein was incorporated into the sarcomeric thin filaments, the majority of SMA protein was found outside of myofibrils. This distribution pattern suggests dual functions for the up-regulated α-SMA as both a contractile component to affect contractility and as possible effector of early remodeling in non-hypertrophic, non-failing cTnI-ND hearts. Highlights • N-terminal truncated cardiac troponin I (cTnI-ND) upregulates α-smooth muscle actin. • This myocardial hypertrophy marker is expressed early in cardiomyocytes. • Increased relaxation by cTnI-ND has a potent effect on myocardial remodeling. • The majority of α-smooth muscle actin was found outside of myofibrils. |
| Databáze: | OpenAIRE |
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