標題: Imaging of Zebrafish In Vivo with Second-Harmonic Generation Reveals Shortened Sarcomeres Associated with Myopathy Induced by Statin
作者: Huang, Shih-Hao
Hsiao, Chung-Der
Lin, Dar-Shong
Chow, Cho-Yen
Chang, Chia-Jen
Liau, Ian
應用化學系分子科學碩博班
Institute of Molecular science
公開日期: 23-九月-2011
摘要: We employed second-harmonic generation (SHG) imaging and the zebrafish model to investigate the myopathy caused by statin in vivo with emphasis on the altered microstructures of the muscle sarcomere, the fundamental contractile element of muscles. This approach derives an advantage of SHG imaging to observe the striated skeletal muscle of living zebrafish based on signals produced mainly from the thick myosin filament of sarcomeres without employing exogenous labels, and eliminates concern about the distortion of muscle structures caused by sample preparation in conventional histological examination. The treatment with statin caused a significantly shortened sarcomere relative to an untreated control (1.73 +/- 0.09 mu m vs 1.91 +/- 0.08 mu m, P<0.05) while the morphological integrity of the muscle fibers remained largely intact. Mechanistic tests indicated that this microstructural disorder was associated with the biosynthetic pathway of cholesterol, or, specifically, with the impaired production of mevalonate by statins. This microstructural disorder exhibited a strong dependence on both the dosage and the duration of treatment, indicating a possibility to assess the severity of muscle injury according to the altered length of the sarcomeres. In contrast to a conventional assessment of muscle injury using clinical biomarkers in blood, such as creatine kinase that is released from only disrupted myocytes, the ability to determine microstructural modification of sarcomeres allows diagnosis of muscle injury before an onset of conventional clinical symptoms. In light of the increasing prevalence of the incidence of muscle injuries caused by new therapies, our work consolidates the combined use of the zebrafish and SHG imaging as an effective and sensitive means to evaluate the safety profile of new therapeutic targets in vivo.
URI: http://dx.doi.org/10.1371/journal.pone.0024764
http://hdl.handle.net/11536/19071
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0024764
期刊: PLOS ONE
Volume: 6
Issue: 9
結束頁: 
顯示於類別:期刊論文


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