SENP2-mediated SERCA2a deSUMOylation increases calcium overload in cardiomyocytes to aggravate myocardial ischemia/reperfusion injury
Abstract. Background:. Sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) is a key protein that maintains myocardial Ca2+ homeostasis. The present study aimed to investigate the mechanism underlying the SERCA2a-SUMOylation (small ubiquitin-like modifier) process after ischemia/reperfusion injury (I...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer
2023-10-01
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| Series: | Chinese Medical Journal |
| Online Access: | http://journals.lww.com/10.1097/CM9.0000000000002757 |
| _version_ | 1797657215283232768 |
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| author | Yuanyuan Luo Shuaishuai Zhou Tao Xu Wanling Wu Pingping Shang Shuai Wang Defeng Pan Dongye Li Xiuyuan Hao |
| author_facet | Yuanyuan Luo Shuaishuai Zhou Tao Xu Wanling Wu Pingping Shang Shuai Wang Defeng Pan Dongye Li Xiuyuan Hao |
| author_sort | Yuanyuan Luo |
| collection | DOAJ |
| description | Abstract.
Background:. Sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) is a key protein that maintains myocardial Ca2+ 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. |
| first_indexed | 2024-03-11T17:41:16Z |
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| id | doaj.art-d64cbca4b2044251a2508097254457e9 |
| institution | Directory Open Access Journal |
| issn | 0366-6999 2542-5641 |
| language | English |
| last_indexed | 2024-03-11T17:41:16Z |
| publishDate | 2023-10-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | Chinese Medical Journal |
| spelling | doaj.art-d64cbca4b2044251a2508097254457e92023-10-18T09:46:52ZengWolters KluwerChinese Medical Journal0366-69992542-56412023-10-01136202496250710.1097/CM9.0000000000002757202310200-00012SENP2-mediated SERCA2a deSUMOylation increases calcium overload in cardiomyocytes to aggravate myocardial ischemia/reperfusion injuryYuanyuan Luo0Shuaishuai Zhou1Tao Xu2Wanling Wu3Pingping Shang4Shuai Wang5Defeng Pan6Dongye Li7Xiuyuan Hao1 Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221006, China2 Institute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China.2 Institute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China.1 Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221006, China2 Institute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China.2 Institute of Cardiovascular Disease Research, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China.1 Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221006, China1 Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221006, ChinaAbstract. Background:. Sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) is a key protein that maintains myocardial Ca2+ 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.http://journals.lww.com/10.1097/CM9.0000000000002757 |
| spellingShingle | Yuanyuan Luo Shuaishuai Zhou Tao Xu Wanling Wu Pingping Shang Shuai Wang Defeng Pan Dongye Li Xiuyuan Hao SENP2-mediated SERCA2a deSUMOylation increases calcium overload in cardiomyocytes to aggravate myocardial ischemia/reperfusion injury Chinese Medical Journal |
| title | SENP2-mediated SERCA2a deSUMOylation increases calcium overload in cardiomyocytes to aggravate myocardial ischemia/reperfusion injury |
| title_full | SENP2-mediated SERCA2a deSUMOylation increases calcium overload in cardiomyocytes to aggravate myocardial ischemia/reperfusion injury |
| title_fullStr | SENP2-mediated SERCA2a deSUMOylation increases calcium overload in cardiomyocytes to aggravate myocardial ischemia/reperfusion injury |
| title_full_unstemmed | SENP2-mediated SERCA2a deSUMOylation increases calcium overload in cardiomyocytes to aggravate myocardial ischemia/reperfusion injury |
| title_short | SENP2-mediated SERCA2a deSUMOylation increases calcium overload in cardiomyocytes to aggravate myocardial ischemia/reperfusion injury |
| title_sort | senp2 mediated serca2a desumoylation increases calcium overload in cardiomyocytes to aggravate myocardial ischemia reperfusion injury |
| url | http://journals.lww.com/10.1097/CM9.0000000000002757 |
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