- Title
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Inhibition of serum and glucocorticoid regulated kinase-1 as novel therapy for cardiac arrhythmia disorders
- Authors
- Bezzerides, V.J., Zhang, A., Xiao, L., Simonson, B., Khedkar, S.A., Baba, S., Ottaviano, F., Lynch, S., Hessler, K., Rigby, A.C., Milan, D., Das, S., Rosenzweig, A.
- Source
- Full text @ Sci. Rep.
SGK1 inhibition rescues a zebrafish model of long QT. (A) Still frame image of zebrafish heart with chamber labels (A = atrium) (V = ventricle). Representative tracings of chamber wall position demonstrating 2:1 AV block in mutant bkd −/− zebrafish (upper panel) and with rescue of the phenotype (lower panel). (B) Knock-down with SGK1 morpholino or inhibition of SGK1 (500 μM SGK1-DN mRNA) in the breakdance zebrafish mutants with long QT at 1–2 cell stage leads to significant rescue of 2:1 AV block at 99 hpf stage (5% spontaneous reversion at this stage); *p-value < 0.05 by Z-test. (C) Compound 5377051 added at 48 hours post fertilization (hpf) and assessed at 72 hpf for rescue of phenotype 2 with superimposed rescue (solid line) and toxicity (dashed lines) curves shown on left (C) and representative bar graph on right (D). *p < 0.05 by Z-test. PHENOTYPE:
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