FIGURE

Fig. 5

ID
ZDB-FIG-190807-29
Publication
Mishra et al., 2019 - Zebrafish model of amyloid light chain cardiotoxicity: regeneration vs degeneration
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Fig. 5

Proliferation inhibition in transgenic zebrafish using SB431542 sensitizes them to LC cardiac toxicity lowering survival, increasing cardiac cell death and dysfunction. Representative images (left) from isolated control and AL-LC TG embryonic zebrafish hearts following 24-h SB431542 treatment display a decrease in EdU-labeled nuclei. Quantification of EdU-positive cells in zebrafish heart following 24-h SB431542 treatment. n = 5–7 zebrafish embryos/group; P = 0.03 for control embryos with DMSO vs. SB431542; P = 0.02 for TG DMSO vs. SB431542 (A). Dimensional analysis performed as (23) at 72 hpf following a 24-h SB431542 treatment revealed a loss of the cardiac functional compensation by stroke volume (P = 0.02) (B). Kaplan-Meier curve shows that survival is significantly decreased in AL-LC transgenic zebrafish embryos treated with 10 µM SB431542 for 96 h administered starting at 2 days postfertilization (*P = 0.002 for control embryos with SB431542 vs. TG SB431542; **P = 0.0003 for TG with DMSO vs. SB431542); n ≥ 40 zebrafish embryos/group (C). Representative images of isolated control and AL-LC TG zebrafish hearts following 24-h and 96-h SB431542 treatment revealed increased TUNEL-stained nuclei (red, left). Quantification of TUNEL-positive cells in isolated zebrafish hearts following 24-h and 96-h SB431542 treatment. Treatment for both durations resulted in a significant increase in cell death in the AL-LC TG fish hearts, n = 7–14 zebrafish embryos/group; P = 0.02 at 24 h; P = 0.008 at 96 h (D). Further evidence of apoptosis was observed with an increase in cleaved caspase-3 protein by immunoblotting of the AL-LC TG embryos treated with 10 μM SB431542 (P = 0.048) (E). Indication of abnormal authophagic flux was observed via increased LC3-II protein levels as measured by immunoblotting of the AL-LC TG embryos treated with 10 μM SB431542 (P = 0.045). n = 3 separate experiments with 7–14 zebrafish embryos/group (F). Con, control; EdU, 5-ethynyl-2′-deoxyuridine; hpf, hours postfertilization; SB, SB431542; TG, transgenic.

 

Expression Data
Antibodies:
Fish:
Condition:
Anatomical Term:
Stage: Day 6

Expression Detail
Antibody Labeling
Phenotype Data
Fish:
Condition:
Observed In:
Stage Range: Long-pec to Days 14-20

Phenotype Detail
Acknowledgments
This image is the copyrighted work of the attributed author or publisher, and ZFIN has permission only to display this image to its users. Additional permissions should be obtained from the applicable author or publisher of the image. Full text @ Am. J. Physiol. Heart Circ. Physiol.