SENP2-mediated SERCA2a deSUMOylation increases calcium overload in cardiomyocytes to aggravate myocardial ischemia/reperfusion injury.
10.1097/CM9.0000000000002757
- Author:
Yuanyuan LUO
1
;
Shuaishuai ZHOU
2
;
Tao XU
2
;
Wanling WU
1
;
Pingping SHANG
2
;
Shuai WANG
2
;
Defeng PAN
1
;
Dongye LI
1
Author Information
1. Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221006, China.
2. Institute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Mice;
Calcium/metabolism*;
Cysteine Endopeptidases/metabolism*;
Myocardial Reperfusion Injury/metabolism*;
Myocardium/metabolism*;
Myocytes, Cardiac/metabolism*;
Proteins/metabolism*;
Sarcoplasmic Reticulum Calcium-Transporting ATPases/genetics*
- From:
Chinese Medical Journal
2023;136(20):2496-2507
- CountryChina
- Language:English
-
Abstract:
BACKGROUND:Sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) is a key protein that maintains myocardial Ca 2+ homeostasis. The present study aimed to investigate the mechanism underlying the SERCA2a-SUMOylation (small ubiquitin-like modifier) process after ischemia/reperfusion injury (I/RI) in vitro and in vivo .
METHODS:Calcium transient and systolic/diastolic function of cardiomyocytes isolated from Serca2a knockout (KO) and wild-type mice with I/RI were compared. SUMO-relevant protein expression and localization were detected by quantitative real-time PCR (RT-qPCR), Western blotting, and immunofluorescence in vitro and in vivo . Serca2a-SUMOylation, infarct size, and cardiac function of Senp1 or Senp2 overexpressed/suppressed adenovirus infected cardiomyocytes, were detected by immunoprecipitation, triphenyltetrazolium chloride (TTC)-Evans blue staining, and echocardiography respectively.
RESULTS:The results showed that the changes of Fura-2 fluorescence intensity and contraction amplitude of cardiomyocytes decreased in the I/RI groups and were further reduced in the Serca2a KO + I/RI groups. Senp1 and Senp2 messenger ribose nucleic acid (mRNA) and protein expression levels in vivo and in cardiomyocytes were highest at 6 h and declined at 12 h after I/RI. However, the highest levels in HL-1 cells were recorded at 12 h. Senp2 expression increased in the cytoplasm, unlike that of Senp1. Inhibition of Senp2 protein reversed the I/RI-induced Serca2a-SUMOylation decline, reduced the infarction area, and improved cardiac function, while inhibition of Senp1 protein could not restore the above indicators.
CONCLUSION:I/RI activated Senp1 and Senp2 protein expression, which promoted Serca2a-deSUMOylation, while inhibition of Senp2 expression reversed Serca2a-SUMOylation and improved cardiac function.
