Downregulation of cardiac PIASy inhibits Cx43 SUMOylation and ameliorates ventricular arrhythmias in a rat model of myocardial ischemia/reperfusion injury
Abstract. Background:. Dysfunction of the gap junction channel protein connexin 43 (Cx43) contributes to myocardial ischemia/reperfusion (I/R)-induced ventricular arrhythmias. Cx43 can be regulated by small ubiquitin-like modifier (SUMO) modification. Protein inhibitor of activated STAT Y (PIASy) is...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer
2023-06-01
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| Series: | Chinese Medical Journal |
| Online Access: | http://journals.lww.com/10.1097/CM9.0000000000002618 |
| _version_ | 1797801037345587200 |
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| author | Tingting Wang Jinmin Liu Chenchen Hu Xin Wei Linlin Han Afang Zhu Rong Wang Zhijun Chen Zhengyuan Xia Shanglong Yao Weike Mao Rongman Jia Xiuyuan Hao |
| author_facet | Tingting Wang Jinmin Liu Chenchen Hu Xin Wei Linlin Han Afang Zhu Rong Wang Zhijun Chen Zhengyuan Xia Shanglong Yao Weike Mao Rongman Jia Xiuyuan Hao |
| author_sort | Tingting Wang |
| collection | DOAJ |
| description | Abstract. Background:. Dysfunction of the gap junction channel protein connexin 43 (Cx43) contributes to myocardial ischemia/reperfusion (I/R)-induced ventricular arrhythmias. Cx43 can be regulated by small ubiquitin-like modifier (SUMO) modification. Protein inhibitor of activated STAT Y (PIASy) is an E3 SUMO ligase for its target proteins. However, whether Cx43 is a target protein of PIASy and whether Cx43 SUMOylation plays a role in I/R-induced arrhythmias are largely unknown.
Methods:. Male Sprague–Dawley rats were infected with PIASy short hairpin ribonucleic acid (shRNA) using recombinant adeno-associated virus subtype 9 (rAAV9). Two weeks later, the rats were subjected to 45 min of left coronary artery occlusion followed by 2 h reperfusion. Electrocardiogram was recorded to assess arrhythmias. Rat ventricular tissues were collected for molecular biological measurements.
Results:. Following 45 min of ischemia, QRS duration and QTc intervals statistically significantly increased, but these values decreased after transfecting PIASy shRNA. PIASy downregulation ameliorated ventricular arrhythmias induced by myocardial I/R, as evidenced by the decreased incidence of ventricular tachycardia and ventricular fibrillation, and reduced arrythmia score. In addition, myocardial I/R statistically significantly induced PIASy expression and Cx43 SUMOylation, accompanied by reduced Cx43 phosphorylation and plakophilin 2 (PKP2) expression. Moreover, PIASy downregulation remarkably reduced Cx43 SUMOylation, accompanied by increased Cx43 phosphorylation and PKP2 expression after I/R.
Conclusion:. PIASy downregulation inhibited Cx43 SUMOylation and increased PKP2 expression, thereby improving ventricular arrhythmias in ischemic/reperfused rats heart. |
| first_indexed | 2024-03-13T04:44:19Z |
| format | Article |
| id | doaj.art-4d8323663db240508f2e909ca0612075 |
| institution | Directory Open Access Journal |
| issn | 0366-6999 2542-5641 |
| language | English |
| last_indexed | 2024-03-13T04:44:19Z |
| publishDate | 2023-06-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | Chinese Medical Journal |
| spelling | doaj.art-4d8323663db240508f2e909ca06120752023-06-19T02:42:45ZengWolters KluwerChinese Medical Journal0366-69992542-56412023-06-01136111349135710.1097/CM9.0000000000002618202306050-00009Downregulation of cardiac PIASy inhibits Cx43 SUMOylation and ameliorates ventricular arrhythmias in a rat model of myocardial ischemia/reperfusion injuryTingting WangJinmin LiuChenchen HuXin WeiLinlin HanAfang ZhuRong WangZhijun ChenZhengyuan XiaShanglong YaoWeike MaoRongman JiaXiuyuan HaoAbstract. Background:. Dysfunction of the gap junction channel protein connexin 43 (Cx43) contributes to myocardial ischemia/reperfusion (I/R)-induced ventricular arrhythmias. Cx43 can be regulated by small ubiquitin-like modifier (SUMO) modification. Protein inhibitor of activated STAT Y (PIASy) is an E3 SUMO ligase for its target proteins. However, whether Cx43 is a target protein of PIASy and whether Cx43 SUMOylation plays a role in I/R-induced arrhythmias are largely unknown. Methods:. Male Sprague–Dawley rats were infected with PIASy short hairpin ribonucleic acid (shRNA) using recombinant adeno-associated virus subtype 9 (rAAV9). Two weeks later, the rats were subjected to 45 min of left coronary artery occlusion followed by 2 h reperfusion. Electrocardiogram was recorded to assess arrhythmias. Rat ventricular tissues were collected for molecular biological measurements. Results:. Following 45 min of ischemia, QRS duration and QTc intervals statistically significantly increased, but these values decreased after transfecting PIASy shRNA. PIASy downregulation ameliorated ventricular arrhythmias induced by myocardial I/R, as evidenced by the decreased incidence of ventricular tachycardia and ventricular fibrillation, and reduced arrythmia score. In addition, myocardial I/R statistically significantly induced PIASy expression and Cx43 SUMOylation, accompanied by reduced Cx43 phosphorylation and plakophilin 2 (PKP2) expression. Moreover, PIASy downregulation remarkably reduced Cx43 SUMOylation, accompanied by increased Cx43 phosphorylation and PKP2 expression after I/R. Conclusion:. PIASy downregulation inhibited Cx43 SUMOylation and increased PKP2 expression, thereby improving ventricular arrhythmias in ischemic/reperfused rats heart.http://journals.lww.com/10.1097/CM9.0000000000002618 |
| spellingShingle | Tingting Wang Jinmin Liu Chenchen Hu Xin Wei Linlin Han Afang Zhu Rong Wang Zhijun Chen Zhengyuan Xia Shanglong Yao Weike Mao Rongman Jia Xiuyuan Hao Downregulation of cardiac PIASy inhibits Cx43 SUMOylation and ameliorates ventricular arrhythmias in a rat model of myocardial ischemia/reperfusion injury Chinese Medical Journal |
| title | Downregulation of cardiac PIASy inhibits Cx43 SUMOylation and ameliorates ventricular arrhythmias in a rat model of myocardial ischemia/reperfusion injury |
| title_full | Downregulation of cardiac PIASy inhibits Cx43 SUMOylation and ameliorates ventricular arrhythmias in a rat model of myocardial ischemia/reperfusion injury |
| title_fullStr | Downregulation of cardiac PIASy inhibits Cx43 SUMOylation and ameliorates ventricular arrhythmias in a rat model of myocardial ischemia/reperfusion injury |
| title_full_unstemmed | Downregulation of cardiac PIASy inhibits Cx43 SUMOylation and ameliorates ventricular arrhythmias in a rat model of myocardial ischemia/reperfusion injury |
| title_short | Downregulation of cardiac PIASy inhibits Cx43 SUMOylation and ameliorates ventricular arrhythmias in a rat model of myocardial ischemia/reperfusion injury |
| title_sort | downregulation of cardiac piasy inhibits cx43 sumoylation and ameliorates ventricular arrhythmias in a rat model of myocardial ischemia reperfusion injury |
| url | http://journals.lww.com/10.1097/CM9.0000000000002618 |
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