Protein Quality Control Disruption by PKCβII in Heart Failure; Rescue by the Selective PKCβII Inhibitor, βIIV5-3
Figure 6
Impaired protein quality control in left ventricular remodeling and heart failure in humans.
A. ATP-dependent and -independent proteasomal activity, B. oxidized protein levels (determined by Western blot) and C. polyubiquitinated protein levels (determined by Western blot) in biopsied hearts from aortic stenosis-induced left ventricular remodeling (LVR) patients (green bars), ischemic cardiomyopathy-induced heart failure patients (red bars) and autopsied non-failing human hearts (white bars). D. Negative correlation between proteasomal function and oxidized protein accumulation in failing (aortic stenosis-LVR and ischemic-HF) and non-failing heart samples. E. Total PKC levels in failing hearts compared to non-failing hearts and F. Representative blots of PKCβII and PKCα proteins in total and Triton-soluble fraction (particulate fraction) in biopsied hearts from aortic stenosis-induced left ventricular remodeling patients (n = 6, green bars) and ischemic cardiomyopathy-induced heart failure patients (n = 3, red bars) compared to autopsied non-failing human hearts (n = 6, trace). Total and Triton-soluble fractions were normalized against GAPDH and Gαo, respectively. Error bars indicate SEM. *, p<0.05 compared to control (non-failing heart). §, p<0.05 compared to aortic stenosis-LVR patients.