ZFIN ID: ZDB-PUB-130722-4
Silencing of FABP3 leads to apoptosis-induced mitochondrial dysfunction and stimulates Wnt signaling in zebrafish
Liu, Y.Q., Song, G.X., Liu, H.L., Wang, X.J., Shen, Y.H., Zhou, L.J., Jin, J., Liu, M., Shi, C.M., and Qian, L.M.
Date: 2013
Source: Molecular Medicine Reports   8(3): 806-12 (Journal)
Registered Authors:
Keywords: none
MeSH Terms:
  • Adenosine Triphosphate/metabolism
  • Animals
  • Apoptosis/drug effects*
  • DNA Copy Number Variations/drug effects
  • DNA, Mitochondrial/metabolism
  • Embryo, Nonmammalian/metabolism
  • Fatty Acid-Binding Proteins/antagonists & inhibitors*
  • Fatty Acid-Binding Proteins/metabolism
  • Heart/drug effects
  • Heart/growth & development
  • Larva/metabolism
  • Mitochondria/drug effects
  • Mitochondria/genetics
  • Mitochondria/metabolism*
  • Morpholinos/chemistry
  • Morpholinos/toxicity*
  • Reactive Oxygen Species/metabolism
  • Transcription Factors/metabolism
  • Wnt Proteins/metabolism
  • Wnt Signaling Pathway
  • Zebrafish/growth & development
  • Zebrafish/metabolism
  • Zebrafish Proteins/antagonists & inhibitors*
  • Zebrafish Proteins/metabolism
PubMed: 23846528 Full text @ Mol. Med. Rep.
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ABSTRACT

Fatty acid binding protein 3 (FABP3, also termed hearttype fatty acid binding protein) is a member of the intracellular lipidbinding protein family that may be essential in fatty acid transport, cell growth, cellular signaling and gene transcription. Previously, we demonstrated that FABP3 was involved in apoptosisassociated congenital cardiac malformations; however, its mechanism of regulation remains unclear. Apoptosis has increasingly been considered to be important in cardiac development. In the present study, a zebrafish model was used to investigate the involvement of FABP3morpholino (MO)induced apoptosis and mitochondrial dysfunction in cardiac development. During the early stages of cardiac development, injection of FABP3MO into zebrafish resulted in significant impairment in cardiac development and promoted the rate of apoptosis which was correlated with signicant dysfunction of the mitochondria. For example, the ATP content was markedly decreased at 24 and 48 h postfertilization (pf), reactive oxygen species production was significantly enhanced at 24 and 48 h pf and the mitochondrial DNA copy number was reduced at 24, 48 and 72 h pf. Additionally, Nkx2.5 expression was upregulated in FABP3-MO zebrafish, and Wnt signaling molecules (Wnt1, Wnt5 and Wnt11) were also highly expressed in FABP3-MO zebrafish at 24, 48 and 72 h pf. In conclusion, the results indicated that FABP3 knockdown exhibited significant toxic effects on cardiac development and mitochondrial function, which may be responsible for the knockdown of FABP3induced apoptosis. Apoptosis was one of the mechanisms underlying this effect, and was correlated with the activation of Wnt signaling. These studies identified FABP3 as a candidate gene underlying the etiology of congenital heart defects.

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