Ahf-Caltide, a Novel Polypeptide Derived from Calpastatin, Protects against Oxidative Stress Injury by Stabilizing the Expression of Ca V 1.2 Calcium Channel.

Reperfusion after ischemia would cause massive myocardial injury, which leads to oxidative stress (OS). Calcium homeostasis imbalance plays an essential role in myocardial OS injury. Ca V 1.2 calcium channel mediates calcium influx into cardiomyocytes, and its activity is modulated by a region of calpastatin (CAST) domain L, CS L 54-64. In this study, the effect of Ahf-caltide, derived from CS L 54-64, on myocardial OS injury was investigated. Ahf-caltide decreased the levels of LDH, MDA and ROS and increased heart rate, coronary flow, cell survival and SOD activity during OS. In addition, Ahf-caltide permeated into H9c2 cells and increased Ca V 1.2, Ca V β2 and CAST levels by inhibiting protein degradation. At different Ca 2+ concentrations (25 nM, 10 μM, 1 mM), the binding of CS L to the IQ motif in the C terminus of the Ca V 1.2 channel was increased in a H 2 O 2 concentration-dependent manner. CS L 54-64 was predicted to be responsible for the binding of CS L to Ca V 1.2. In conclusion, Ahf-caltide exerted a cardioprotective effect on myocardial OS injury by stabilizing Ca V 1.2 protein expression. Our study, for the first time, proposed that restoring calcium homeostasis by targeting the Ca V 1.2 calcium channel and its regulating factor CAST could be a novel treatment for myocardial OS injury.