Ahf-Caltide, a Novel Polypeptide Derived from Calpastatin, Protects against Oxidative Stress Injury by Stabilizing the Expression of Ca<sub>V</sub>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<sub>V</sub>1.2 calcium channel mediates calcium influx into cardiomyocytes, and its activity is modula...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-10-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/21/15729 |
| Summary: | 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<sub>V</sub>1.2 calcium channel mediates calcium influx into cardiomyocytes, and its activity is modulated by a region of calpastatin (CAST) domain L, CS<sub>L</sub>54-64. In this study, the effect of Ahf-caltide, derived from CS<sub>L</sub>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<sub>V</sub>1.2, Ca<sub>V</sub>β2 and CAST levels by inhibiting protein degradation. At different Ca<sup>2+</sup> concentrations (25 nM, 10 μM, 1 mM), the binding of CS<sub>L</sub> to the IQ motif in the C terminus of the Ca<sub>V</sub>1.2 channel was increased in a H<sub>2</sub>O<sub>2</sub> concentration-dependent manner. CS<sub>L</sub>54-64 was predicted to be responsible for the binding of CS<sub>L</sub> to Ca<sub>V</sub>1.2. In conclusion, Ahf-caltide exerted a cardioprotective effect on myocardial OS injury by stabilizing Ca<sub>V</sub>1.2 protein expression. Our study, for the first time, proposed that restoring calcium homeostasis by targeting the Ca<sub>V</sub>1.2 calcium channel and its regulating factor CAST could be a novel treatment for myocardial OS injury. |
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| ISSN: | 1661-6596 1422-0067 |