title: Silencing of FABP3 leads to apoptosis-induced mitochondrial dysfunction and stimulates Wnt signaling in zebrafish.
abstract: Fatty acid binding protein 3 (FABP3, also termed heart-type fatty acid binding protein) is a member of the intracellular lipid-binding 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 apoptosis-associated 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 FABP3‑morpholino (MO)-induced apoptosis and mitochondrial dysfunction in cardiac development. During the early stages of cardiac development, injection of FABP3‑MO into zebrafish resulted in significant impairment in cardiac development and promoted the rate of apoptosis which was correlated with signiﬁcant dysfunction of the mitochondria. For example, the ATP content was markedly decreased at 24 and 48 h post-fertilization (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 FABP3-induced 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.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Pediatrics, Nanjing Maternity and Child Health Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210029, P.R China.
authors.forename: Yao-Qiu
authors.initials: YQ
authors.lastname: Liu
authors.forename: Gui-Xian
authors.initials: GX
authors.lastname: Song
authors.forename: Hai-Lang
authors.initials: HL
authors.lastname: Liu
authors.forename: Xue-Jie
authors.initials: XJ
authors.lastname: Wang
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Shen
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Zhou
authors.forename: Jin
authors.initials: J
authors.lastname: Jin
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Shi
authors.forename: Ling-Mei
authors.initials: LM
authors.lastname: Qian
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D056915:DNA Copy Number Variations / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000254:growth & development; D000072576:Homeobox Protein Nkx-2.5; D007814:Larva / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D060172:Morpholinos / Q000737:chemistry / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway; D015027:Zebrafish / Q000254:growth & development / Q000378:metabolism; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; C476998:Fabp3 protein, zebrafish; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D000072576:Homeobox Protein Nkx-2.5; D060172:Morpholinos; C528182:Nkx2.5 protein, zebrafish; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D000255:Adenosine Triphosphate