Mutation of a single cysteine in CaMKIIδ protects the heart from ischemia-reperfusion Injury

Figures

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  Figure 1.. CaMKIIδC273S and wild-type mice echocardiogram under basal conditions. (A) The CaMKIIδC273S mouse genotype was confirmed by sequencing of tail tip DNA samples. (B) Wild-type (grey) and CaMKIIδC273S (red) ejection fraction. (C) Wild-type (grey) and CaMKIIδC273S (red) left ventricular diastolic volume. (D) Wild-type (grey) and CaMKIIδC273S (red) left ventricular systolic volume. Wild-type n=11, CaMKIIδC273S n=12. The difference between the groups was statistically non-significant with the unpaired two-tailed t-test.

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  Figure 2.. CaMKIIδC273S and wild-type mice dobutamine stress test. (A) Wild-type (grey) and CaMKIIδC273S (red) ejection fraction at baseline, low dobutamine dose (10 μg/kg/min), or high dobutamine dose (40 μg/kg/min). (B) Wild-type (grey) and CaMKIIδC273S (red) heartbeat rate at baseline, low dobutamine dose (10 μg/kg/min), or high dobutamine dose (40 μg/kg/min). Wild-type n=11, CaMKIIδC273S n=12. The comparison between wild-type and CaMKIIδC273S was statistically non-significant with the unpaired two-tailed t-test. Both wild-type and CaMKIIδC273S ejection fraction and heartbeat were statistically significantly higher after the high dobutamine dose with the unpaired two-tailed t-test.

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  Figure 3.. Postischemic left ventricular rate pressure (RPP) functional recovery and infarct size. (A) Scheme showing ischemia-reperfusion process in the Langendorff perfused heart model. (B) Wild-type (grey) and CaMKIIδC273S (red) postischemic left ventricular rate times pressure (RPP) as a functional measure of recovery. (C) Wild-type (grey) and CaMKIIδC273S (red) infarct area. Wild-type n=7, CaMKIIδC273S n=8. ****, p <0.0001. **, p = 0.003 with the unpaired two-tailed t-test.

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  Figure 4.. Rate of degradation of wild-type and C273S CaMKIIδ in HEK293T cells. (A) HEK293T cells transfected with wild-type or C273S CaMKIIδ were treated with 50 μg/ml cycloheximide (CHX) for 1, 2, or 3 hours. Cells were lysed, and the supernatant was probed with anti-CaMKII antibody. Representative image of n = 3 replicates. (B) CaMKIIδ remaining wild-type (grey) and C273S CaMKIIδ (red). The level of CaMKIIδ at 0 h was set to 100%.