β-Lapachone induces heart morphogenetic and functional defects by promoting the death of erythrocytes and the endocardium in zebrafish embryos

Wu, Yi-Ting; Lin, Che Yi; Tsai, Ming‐Fa; Chen, Yihua; Lu, Yu-Fen; Huang, Chang-Jen; Cheng, Chao‐Min; Hwang, Sheng-Ping L.

doi:10.1186/1423-0127-18-70

Cited by 13 publications

(5 citation statements)

References 54 publications

(61 reference statements)

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“…To measure intestinal ROS production in zebrafish in vivo, zebrafish were incubated with CM-H2DCFDA (0.5 µg/mL, Thermofisher C6827, diluted in gnotobiotic medium) for 1 hr as indicated by previous studies (Wu et al, 2011). The zebrafish were then washed with GZM and imaged immediately using an stereofluorescence microcope (Leica M205 FA microscope equipped with a Leica DFC 365FX camera).…”

Section: Methodsmentioning

confidence: 99%

High fat diet induces microbiota-dependent silencing of enteroendocrine cells

Mueller

Bagwell

et al. 2019

eLife

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Enteroendocrine cells (EECs) are specialized sensory cells in the intestinal epithelium that sense and transduce nutrient information. Consumption of dietary fat contributes to metabolic disorders, but EEC adaptations to high fat feeding were unknown. Here, we established a new experimental system to directly investigate EEC activity in vivo using a zebrafish reporter of EEC calcium signaling. Our results reveal that high fat feeding alters EEC morphology and converts them into a nutrient insensitive state that is coupled to endoplasmic reticulum (ER) stress. We called this novel adaptation 'EEC silencing'. Gnotobiotic studies revealed that germ-free zebrafish are resistant to high fat diet induced EEC silencing. High fat feeding altered gut microbiota composition including enrichment of Acinetobacter bacteria, and we identified an Acinetobacter strain sufficient to induce EEC silencing. These results establish a new mechanism by which dietary fat and gut microbiota modulate EEC nutrient sensing and signaling.

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Section: Methodsmentioning

confidence: 99%

High fat diet induces microbiota-dependent silencing of enteroendocrine cells

Mueller

Bagwell

et al. 2019

eLife

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“…All the experiments were performed in compliance with the approval of USC Institutional Animal Care and Use Committee (IACUC) protocol (Zebrafish IACUC Protocol number: 11767). These fish were maintained with filtered fresh water under 14 hours of incandescent light and 10 hours of dark conditions [20]. The fli1a promoter-driven enhanced green fluorescent protein (GFP) is expressed predominantly in vascular endothelial and endocardial cells.…”

Section: Methodsmentioning

confidence: 99%

“…The composition of zebrafish blood was assumed to be similar to that of humans, and viscosity was estimated from the relative viscosity and particle volume fraction using literature data [2,24]. The obtained value, 7 centipoise (cP), was close to that of the trout (8cP) [20]. The density of blood was assumed to be similar to that of humans (1.06g/cm 2 ).…”

Section: Methodsmentioning

confidence: 99%

Moving Domain Computational Fluid Dynamics to Interface with an Embryonic Model of Cardiac Morphogenesis

et al. 2013

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Peristaltic contraction of the embryonic heart tube produces time- and spatial-varying wall shear stress (WSS) and pressure gradients (∇P) across the atrioventricular (AV) canal. Zebrafish (Danio rerio) are a genetically tractable system to investigate cardiac morphogenesis. The use of Tg(fli1a:EGFP)y1 transgenic embryos allowed for delineation and two-dimensional reconstruction of the endocardium. This time-varying wall motion was then prescribed in a two-dimensional moving domain computational fluid dynamics (CFD) model, providing new insights into spatial and temporal variations in WSS and ∇P during cardiac development. The CFD simulations were validated with particle image velocimetry (PIV) across the atrioventricular (AV) canal, revealing an increase in both velocities and heart rates, but a decrease in the duration of atrial systole from early to later stages. At 20-30 hours post fertilization (hpf), simulation results revealed bidirectional WSS across the AV canal in the heart tube in response to peristaltic motion of the wall. At 40-50 hpf, the tube structure undergoes cardiac looping, accompanied by a nearly 3-fold increase in WSS magnitude. At 110-120 hpf, distinct AV valve, atrium, ventricle, and bulbus arteriosus form, accompanied by incremental increases in both WSS magnitude and ∇P, but a decrease in bi-directional flow. Laminar flow develops across the AV canal at 20-30 hpf, and persists at 110-120 hpf. Reynolds numbers at the AV canal increase from 0.07±0.03 at 20-30 hpf to 0.23±0.07 at 110-120 hpf (p< 0.05, n=6), whereas Womersley numbers remain relatively unchanged from 0.11 to 0.13. Our moving domain simulations highlights hemodynamic changes in relation to cardiac morphogenesis; thereby, providing a 2-D quantitative approach to complement imaging analysis.

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“…It was well established that during the developmental period, humans, rats, mice, and zebrafish exhibit heightened susceptibility to oxidative stress induced by excessive ROS production, which is implicated in the pathogenesis of CHDs . Several studies showed that ROS overproduction was integral and important in zebrafish cardiac malformations induced by PM 2.5 , trichloroethylene, β-lapachone, and benzo(a)pyrene. ,− High salt exposure also induced cardiac tube malformation during protozoan embryogenesis by producing excessive ROS . Numerous studies documented ROS overproduction induced by PM 2.5 exposure (Table S1).…”

Section: The Aop On Pm25 Induced Cardiac Developmental Toxicitymentioning

confidence: 99%

An Overview of Adverse Outcome Pathway Links between PM_2.5 Exposure and Cardiac Developmental Toxicity

Liang,

Ding,

Sun

et al. 2024

Environ. Health

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Fine particulate matter (PM 2.5 ) is a significant risk factor for birth defects. As the first and most important organ to develop during embryogenesis, the heart's potential susceptibility to PM 2.5 has attracted growing concern. Despite several studies supporting the cardiac developmental toxicity of PM 2.5 , the diverse study types, models, and end points have prevented the integration of mechanisms. In this Review, we present an adverse outcome pathway framework to elucidate the association between PM 2.5 -induced molecular initiating events and adverse cardiac developmental outcomes. Activation of the aryl hydrocarbon receptor (AhR) and excessive generation of reactive oxygen species (ROS) were considered as molecular initiating events. The excessive production of ROS induced oxidative stress, endoplasmic reticulum stress, DNA damage, and inflammation, resulting in apoptosis. The activation of the AhR inhibited the Wnt/β-catenin pathway and then suppressed cardiomyocyte differentiation. Impaired cardiomyocyte differentiation and persistent apoptosis resulted in abnormalities in the cardiac structure and function. All of the aforementioned events have been identified as key events (KEs). The culmination of these KEs ultimately led to the adverse outcome, an increased morbidity of congenital heart defects (CHDs). This work contributes to understanding the causes of CHDs and promotes the safety evaluation of PM 2.5.

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β-Lapachone induces heart morphogenetic and functional defects by promoting the death of erythrocytes and the endocardium in zebrafish embryos

Cited by 13 publications

References 54 publications

High fat diet induces microbiota-dependent silencing of enteroendocrine cells

High fat diet induces microbiota-dependent silencing of enteroendocrine cells

Moving Domain Computational Fluid Dynamics to Interface with an Embryonic Model of Cardiac Morphogenesis

An Overview of Adverse Outcome Pathway Links between PM_2.5 Exposure and Cardiac Developmental Toxicity

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β-Lapachone induces heart morphogenetic and functional defects by promoting the death of erythrocytes and the endocardium in zebrafish embryos

Cited by 13 publications

References 54 publications

High fat diet induces microbiota-dependent silencing of enteroendocrine cells

High fat diet induces microbiota-dependent silencing of enteroendocrine cells

Moving Domain Computational Fluid Dynamics to Interface with an Embryonic Model of Cardiac Morphogenesis

An Overview of Adverse Outcome Pathway Links between PM2.5 Exposure and Cardiac Developmental Toxicity

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Product

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An Overview of Adverse Outcome Pathway Links between PM_2.5 Exposure and Cardiac Developmental Toxicity