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. CaV 1.2 calcium channel mediates calcium influx into cardiomyocytes, and its activity is modulated by a region of calpastatin (CAST) domain L, CSL 54-64. In this study, the effect of Ahf-caltide, derived from CSL 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 CaV 1.2, CaV β2 and CAST levels by inhibiting protein degradation. At different Ca2+ concentrations (25 nM, 10 μM, 1 mM), the binding of CSL to the IQ motif in the C terminus of the CaV 1.2 channel was increased in a H2 O2 concentration-dependent manner. CSL 54-64 was predicted to be responsible for the binding of CSL to CaV 1.2. In conclusion, Ahf-caltide exerted a cardioprotective effect on myocardial OS injury by stabilizing CaV 1.2 protein expression. Our study, for the first time, proposed that restoring calcium homeostasis by targeting the CaV 1.2 calcium channel and its regulating factor CAST could be a novel treatment for myocardial OS injury.