Calenduloside E suppresses calcium overload by promoting the interaction between L-type calcium channels and Bcl2-associated athanogene 3 to alleviate myocardial ischemia/reperfusion injury.

Abstract

Introduction:

Intracellular calcium overload is an important contributor to myocardial ischemia/reperfusion (MI/R) injury. Total saponins of the traditional Chinese medicinal plant Aralia elata (Miq.) Seem. (AS) are beneficial for treating MI/R injury, and Calenduloside E (CE) is the main active ingredient of AS.

Objectives:

This study aimed to investigate the effects of CE on MI/R injury and determine its specific regulatory mechanisms.

Methods:

To verify whether CE mediated cardiac protection in vivo and in vitro, we performed MI/R surgery in SD rats and subjected neonatal rat ventricular myocytes (NRVMs) to hypoxia-reoxygenation (HR). CE's cardioprotective against MI/R injury was detected by Evans blue/TTC staining, echocardiography, HE staining, myocardial enzyme levels. Impedance and field potential recording, and patch-clamp techniques of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were used to detect the function of L-type calcium channels (LTCC). The mechanisms underlying between CE and LTCC was studied through western blot, immunofluorescence, and immunohistochemistry. Drug affinity responsive target stability (DARTS) and co-immunoprecipitation (co-IP) used to further clarify the effect of CE on LTCC and BAG3.

Results:

We found that CE protected against MI/R injury by inhibiting calcium overload. Furthermore, CE improved contraction and field potential signals of hiPSC-CMs and restored sarcomere contraction and calcium transient of adult rat ventricular myocytes (ARVMs). Moreover, patch-clamp data showed that CE suppressed increased L-type calcium current (ICa,L) caused by LTCC agonist, proving that CE could regulate calcium homeostasis through LTCC. Importantly, we found that CE promoted the interaction between LTCC and Bcl2-associated athanogene 3 (BAG3) by co-IP and DARTS.

Conclusion:

Our results demonstrate that CE enhanced LTCC-BAG3 interaction to reduce MI/R induced-calcium overload, exerting a cardioprotective effect.

• Authors: Ruiying Wang, Min Wang, Jiahui Zhou, Ziru Dai, Guibo Sun, Xiaobo Sun
• Journal: Journal of advanced research (J Adv Res) Vol. 34 Pg. 173-186 (12 2021) ISSN: 2090-1224 [Electronic] Egypt
• PMID: 35024189 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Published by Elsevier B.V. on behalf of Cairo University.

Chemical References

• Adaptor Proteins, Signal Transducing
• Apoptosis Regulatory Proteins
• BAG3 protein, rat
• Calcium Channels, L-Type
• Saponins
• calenduloside E
• Oleanolic Acid
• Calcium

Topics

• Adaptor Proteins, Signal Transducing
• Animals
• Apoptosis
• Apoptosis Regulatory Proteins
• Calcium (metabolism)
• Calcium Channels, L-Type (genetics)
• Myocardial Reperfusion Injury (drug therapy)
• Oleanolic Acid (analogs & derivatives)
• Rats
• Rats, Sprague-Dawley
• Saponins (pharmacology)