Molecular mechanism of curcumin-induced myopathy in zebrafish
Date Issued
2015
Date
2015
Author(s)
Huang, Yi- Lin
Abstract
Abstract Curcumin (diferuloylmethane) is a pigment derived from the plant species Curcuma longa, which is frequently added in food for spice. In addition, it has been reported to be a new member of the histone deacetylase (HDAC) inhibitors and anti- cancer drug. In our previous studies, we found that curcumin functioned in inducing myopathy in zebrafish embryos during early developmental stages. In this study, our data indicated that curcumin- induced myopathy were in a dose and temperature- dependent manner. Then, a time-lapse recording was shown curcumin- induced myopathy with continuous damages. On the other hand, we used tissue specific transgenic lines to label keratinocytes and muscle cells (krt4:mCherry, ap:GFP). After the muscle damage occurred, the muscle cells and keratinocytes started to collapse and released the component proteins of the cells. We then detected these proteins in Mass analysis. The in situ hybridization and whole mount immunostaining analysis were performed to analyze this myopathy of zebrafish embryo. We found that the expression of laminin, a protein for tail bud and membrane structure, was decreased in curcumin treated embryos. To investigate possible mechanism of curcumin- induded myopathy in zebrafish embryos, we injected morpholino (MO) to knock down HDCA1 and HDAC8 expression, but it couldn’t recapitulate the phenotype of curcumin- induced myopathy. Finally, we used this zebrafish model to screen several known inhibitors, such as apoptosis inhibitors, autophagy inhibitors and immunosuppressors with the roles to inhibit the progression of curcumin-induced myopathy. Interestingly, a TOR independent autophagy inducer, inhibited curcumin- induced myopathy effectively.
Subjects
curcumin
zebrafish
myopathy
trehalose
histone deacetylase
SDGs
Type
thesis
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