Sustained PKCβII inhibition re-establishes protein quality control and improves cardiac function in myocardial infarction-induced model of heart failure.

<p><b>A</b>. Schematic panel of PKCβII treatment in the post-MI heart failure model, representative blots of PKCβII total level and translocation to particulate fraction, and PKCβII activity from left ventricle tissue from 22-week-old myocardial infarction-induced heart failure (10 wks after MI surgery) TAT-treated, βIIV5-3-treated and control (sham) rats (n = 3 per group). <b>B</b>. 20S proteasome subunits (α5/7, β1, β5 and β7) were precipitated from left ventricle tissue from 22-week-old myocardial infarction-induced heart failure (10 wks after MI surgery) TAT-treated, βIIV5-3-treated and control (sham) rats (n = 3 per group), and then probed with PKCβII, PKCε and anti-serine and threonine phosphorylation antibodies. Equal sample loading was verified using α5/7, β1, β5 and β7 proteasome subunits antibody. <b>C</b>. ATP-dependent and -independent cardiac proteasomal activity. <b>D</b>. Representative blots of proteasome 20S, α-β-crystallin, HSP27, caspase-3, cleaved caspase-3 and GAPDH in heart samples from 22 week-old rats (10 wks after MI surgery) (n = 6 per group). Data quantification and statistical details are in supplementary <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0033175#pone-0033175-g004" target="_blank">Fig. 4</a>. <b>E</b>. Oxidized protein levels, <b>F</b>. polyubiquitinated protein levels and <b>G</b>. soluble oligomer accumulation in heart samples from control (sham, white bars), TAT-treated (gray bars) and βIIV5-3-treated (green bars) heart failure rats as determined by Western blot (E, F) and slot-blot analysis (G). <b>H</b>. Average fractional shortening data from each group at 16 weeks and 22 weeks. All biochemical analyses were performed in the ventricular remote area. Error bars indicate SEM. *, p<0.05 compared to control (sham) rats. §, p<0.05 compared to βIIV5-3-treated heart failure rats.